levoleucovorin and Rectal-Neoplasms

Aflibercept; a decoy receptor for vascular endothelial growth factors (VEGFs) and placental growth factor (PLGF), in combination with FOLFIRI (leucovorin calcium, fluorouracil, irinotecan hydrochloride) chemotherapy regime, was FDA approved in 2012 as second-line salvage chemotherapy for metastatic colorectal cancer (mCRC). This is the first systematic review, and meta-analysis-based evidence to determine the efficacy and safety of Aflibercept plus FOLFIRI regimen pooling randomized controlled trials and single-arm studies.. PubMed, Cochrane library, Embase, and Clinical trial.gov were systematically searched for published randomized controlled trials, single-arm studies, and national patient programs on aflibercept plus FOLFIRI chemotherapy for the treatment of mCRC till 11/10/2022.. Ten studies met the inclusion criteria comprising 1075 patients for efficacy studies and 2027 patients for safety studies. The pooled prevalences were 18% (95% CI, 5%-37%, p = 0.00) for 12 m PFS and 61% (95% CI, 53-68%, p = 0.00) for 12 m OS. The pooled prevalences were 69% (95% CI, 55-82%, p = 0.00) for any grade 3-4 toxicities, 10% (95% CI, 5-16%, p = 0.00) for grade 3-4 diarrhea, 13% (95% CI, 5-24%, p = 0.00) for grade 3-4 hypertension, 31% (95% CI, 22-40%, p = 0.00) for grade 3-4 neutropenia and 5% (95% CI, 2-7%, p = 0.00) for grade 3-4 venous thromboembolic event.. Our meta-analysis shows that the aflibercept plus FOLFIRI combination shows better survival efficacies however; it is also associated with more high-grade adverse events.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Colorectal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Placenta Growth Factor; Randomized Controlled Trials as Topic; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Rectal Neoplasms

Chemotherapy plus antiangiogenic agents, including bevacizumab, ramucirumab and aflibercept, is a standard second-line treatment for patients with metastatic colorectal cancer, but which specific agents should be selected is ambiguous due to a lack of clear evidence from prospective studies. Previous reports have suggested ramucirumab and aflibercept could be more effective than bevacizumab in patients with high VEGF-D and high VEGF-A, respectively. JCOG2004 is a three-arm, randomized, phase II study to identify predictive biomarkers for these agents in patients who have failed first-line treatment. The study will enroll 345 patients from 52 institutions for 2 years, with progression-free survival in high VEGF-D (bevacizumab vs ramucirumab) and high VEGF-A (bevacizumab vs aflibercept) serving as the primary end point.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Biomarkers; Camptothecin; Clinical Trials, Phase II as Topic; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Oxaliplatin; Prospective Studies; Rectal Neoplasms; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor D

The meta-analysis aimed to assess the clinical efficacy of chemotherapeutic triplet-drug regimen combined with anti-EGFR antibody in patients with initially unresectable metastatic colorectal cancer (mCRC). A systematic literature search was performed in PubMed Publisher. Studies evaluating FOLFOXIRI combine with panitumumab or cetuximab as the therapy for initially unresectable mCRC were included. The primary outcome was objective response rate (ORR) and rate of R0 resections. The secondary outcomes included overall survival (OS), progression-free survival (PFS), and grades 3 or 4 adverse events. R software (version 4.0.2) and RevMan (version 5.3) were used to analyze the extracted data. The studies included were published between 2010 and 2021, involving four single-arm phase II trials and two randomized phase II trials. A total of 6 studies with 282 patients were included. The data showed a significant benefit for the FOLFOXIRI + anti-EGFR antibody arm compared with FOLFOXIRI arm (RR 1.33; 95% CI, 1.13-1.58; I

Topics: Antineoplastic Combined Chemotherapy Protocols; Cetuximab; Clinical Trials, Phase II as Topic; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Panitumumab; Randomized Controlled Trials as Topic; Rectal Neoplasms; Treatment Outcome

Metastasectomy in patients with metastatic colorectal cancer (mCRC) confers a significant survival benefit. We hypothesized that conversion to resectability (C2R) correlates with superior overall survival (OS) in patients with unresectable mCRC.. A prospectively registered systematic review (PROSPERO CRD42015024104) of randomized clinical trials published after 2003 was conducted. Exposure of interest was C2R with a primary outcome of OS. Clinical trials were classified based on difference in C2R between study arms (<2%, 2% to 2.9%, ≥3%). Generalized estimating equations were used to measure associations while adjusting for multiple observations from the same trial.. Of 2902 studies reviewed, 30 satisfied selection criteria (n=13,618 patients). Median C2R was 7.3% (interquartile range [IQR]: 5% to 12.9%), with maximum C2R in the FOLFOX/FOLFIRI+cetuximab arm (28.6%). The median difference in C2R between 2 arms of the same study was 2.3% (IQR: 1.3% to 3.4%) with a maximum difference of 15.4% seen in FOLFOX/FOLFIRI+cetuximab versus FOLFOX/FOLFIRI. Median OS for the entire patient cohort was 20.7 months (IQR: 18.9 to 22.7 mo), with a between group difference of 1.3 months (IQR: -1.2 to 3.6 mo). The median survival difference between the 2 study arms with <2% C2R difference was 0.8 months versus 1.6 months with ≥3% C2R rates . Increasing C2R had an incremental dose-effect response on OS ( P =0.021), and higher response rates correlated with C2R rates ( P =0.003).. C2R occurs infrequently and variably in clinical trials enrolling patients with unresectable mCRC. Prioritization of chemotherapeutic agents that enhance C2R might improve OS of patients.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Cetuximab; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Rectal Neoplasms

A few months ago, results from two randomised phase III trials of total neoadjuvant therapy (TNT) in locally advanced rectal cancer were presented (RAPIDO and PRODIGE 23), consistently showing better short- and long-term outcomes with TNT as compared with standard neoadjuvant long-course chemoradiotherapy (CRT) or short-course radiotherapy (SCRT). These results represent corroborating evidence in support of a practice that many centres had already implemented based on promising preliminary data. Also, they provide new, high-level evidence to endorse TNT as a new management option in the treatment algorithm of stage II-III rectal cancer in those centres where CRT and SCRT have long remained the only accepted standard neoadjuvant treatments. Having two consistently positive trials is certainly reassuring regarding the potential of TNT as a general treatment approach. Nevertheless, substantial differences between these trials pose important challenges in relation to the generalisability and applicability of their results, and translation of the same into practical clinical recommendations. In this article, we address a number of key questions that the RAPIDO and PRODIGE 23 trials have raised among the broad community of gastrointestinal oncologists, proposing an interpretation of the data that may help the decision making, and highlighting grey areas that warrant further investigation.

Topics: Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemoradiotherapy; Clinical Trials, Phase III as Topic; Fluorouracil; Humans; Leucovorin; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Randomized Controlled Trials as Topic; Rectal Neoplasms

The management of patients with locally advanced rectal cancer has improved significantly in the past few years with preoperative radiotherapy (RT) and total mesorectal excision. The rate of local recurrence is now around 5 % while the risk of metastatic recurrence has not been reduced which is about 30 %. The benefit of adjuvant chemotherapy remains questionable apart from patients with ypN+tumor after preoperative chemoradiotherapy (CRT) for whom FOLFOX is an option. In recent years, several therapeutic trials have evaluated the benefit of extending the time between the end of RT and surgery and/or the benefit of neoadjuvant chemotherapy, administered as induction (before RT) or in consolidation (after RT and before surgery). The first results of two positive phase 3 trials, PRODIGE 23 and RAPIDO, have been reported in 2020. The two regimens evaluated in these trials are markedly different but have shown that neoadjuvant chemotherapy significantly reduces the risk of distant metastasis. Current developments largely related to a de-escalation of therapy: organ conservation according to a "Watch and Wait" strategy or local resection of the scar, administration of neoadjuvant chemotherapy without RT. These therapeutic strategies have not yet been validated but should be in the news tomorrow. The purpose of this review is to present recent data reported in patients with locally advanced rectal cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Chemotherapy, Adjuvant; Clinical Trials, Phase III as Topic; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Organ Sparing Treatments; Organoplatinum Compounds; Rectal Neoplasms; Time Factors

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Digestive System Surgical Procedures; Fluorouracil; Focal Nodular Hyperplasia; Humans; Leucovorin; Liver Neoplasms; Male; Oxaliplatin; Prognosis; Rectal Neoplasms

The value of adjuvant chemotherapy in rectal cancer is controversial with opinions varying from 'not be used' since randomized trials have not shown significant gains to 'be used as in colon cancer' as the need is the same and colon and rectal cancers are quite similar. This review will look upon data critically and with open eyes.. With the exception of one randomized phase II trial (ADORE) revealing a significant gain in disease-free survival using one more effective regimen (mFOLFOX) than bolus 5-fluorouracil leucovorin, no new data have been presented. However, bringing up aspects in previous trials, either considered irrelevant for the present situation or overall negative, of what adjuvant treatment can achieve, a small reduction (hazard ratio about 0.8) in the risk of recurrence is present. This reduction is not fundamentally different from that in colon cancer considering that adjuvant treatment for rectal cancer cannot be initiated as rapidly as it can after a colon cancer diagnosis.. Adjuvant chemotherapy after rectal cancer surgery reduces recurrence risks but the benefit is limited and for most patients not clinically relevant. Neoadjuvant therapy can be more effective but results from randomized trials are not yet available.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Clinical Trials, Phase II as Topic; Fluorouracil; Humans; Leucovorin; Organoplatinum Compounds; Oxaliplatin; Randomized Controlled Trials as Topic; Rectal Neoplasms

Multiple primary malignancy is defined as two or more malignancies detected in an individual person. In particular, synchronous quintuple primary malignancy is extremely rare. A 52-year-old male with anal pain and intermittent blood-tinged stool was diagnosed with malignancies in the stomach, jejunum, ascending colon, transverse colon and rectum. He underwent a subtotal gastrectomy, segmental resection of the jejunum and total protocolectomy with end ileostomy. The postoperative pathologic findings were moderate differentiated gastric adenocarcinoma (pT1bN0M0, pStageIA), combined adenocarcinoma and neuroendocrine carcinoma of the jejunum (pT3N0M0, pStageIIA), three mucinous adenocarcinoma of the ascending colon (pT3N0M0, pStageIIA), transverse colon (pT1N0M0, pStageI) and rectum (pT3N1aM0, pStageIIIB). The tumors did not lack MLH-1 and MSH-2 expression, as the markers (bat26, D5S346, bat25, D2S123) suggest MSI-H presence. Adjuvant chemoradiotherapy was started according to regimen, FOLFOX 4 for advanced rectal cancer. Six years post-operation, the patient is currently attending regular follow-ups without recurrence or metastasis.

Topics: Adenocarcinoma, Mucinous; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Cancer Pain; Chemoradiotherapy, Adjuvant; Colectomy; Colonic Neoplasms; Endoscopy, Gastrointestinal; Fluorouracil; Gastrectomy; Gastrointestinal Hemorrhage; Humans; Ileostomy; Jejunal Neoplasms; Leucovorin; Male; Microsatellite Instability; Middle Aged; Neoplasm Staging; Neoplasms, Multiple Primary; Organoplatinum Compounds; Positron Emission Tomography Computed Tomography; Rectal Neoplasms; Stomach Neoplasms; Tomography, X-Ray Computed

A case of acute kidney injury (AKI) strongly suspected to be drug-induced (oxaliplatin and non-steroidal anti-inflammatory drug) is discussed regarding the mechanism of a reduced glomerular filtration rate responsible for the development of AKI. Urinary biochemical tests are useful for the differential diagnosis of pre- renal (functional) AKI and intrinsic (structural) AKI(so-called acute tubular necrosis). In this case, although a comprehensive differential diagnosis using these parameters supported intrinsic AKI, only one pa- rameter, fractional excretion of urea (FEurea), indicated the existence of prerenal AKI. As a result of treatment with the appropriate management of body fluid in addition to avoiding nephrotoxic medications, AKI rapidly improved. FEurea revealed the underlying mechanism of AKI. [Review].

Topics: Acute Kidney Injury; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Diarrhea; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Rectal Neoplasms; Vomiting

Recently, bevacizumab has become a key drug for treatment of metastatic colorectal cancer. Molecularly targeted agents such as bevacizumab can cause life-threatening adverse effects, though they are generally considered less toxic than cytotoxic drugs. Here, we review the case of a 76-year-old male rectal cancer patient with liver metastasis who suffered extensive bowel necrosis after administration of 5-fluorouracil-based chemotherapy with bevacizumab, and required a subtotal colectomy and end-ileostomy. Microscopic findings revealed extensive mucosal necrosis in the resected colon specimen and necrosis at the muscularis propria of the descending colon. Pathological findings suggested that the mucosal damage induced by chemotherapy may be exacerbated by treatment with bevacizumab, resulting in extensive necrosis.

Topics: Aged; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colectomy; Colon; Fatal Outcome; Fluorouracil; Humans; Ileostomy; Leucovorin; Liver Neoplasms; Male; Necrosis; Organoplatinum Compounds; Rectal Neoplasms

A 34-year-old man with a history of rectal cancer was receiving oral chemotherapy [tegafur-uracil (UFT) with leucovorin]. He visited our hospital due to nausea and abdominal pain, and his laboratory data revealed the presence of urinary ketones, hyperglycemia and high anion gap metabolic acidosis, and HbA1c level of 6.8%. Accordingly, we diagnosed fulminant type 1 diabetes. The development of fulminant type 1 diabetes during chemotherapy for malignancy is a rare, but potentially fatal condition. Therefore, clinicians should consider diabetic ketoacidosis in the differential diagnosis when examining chemotherapy patients who present with gastrointestinal symptoms.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Diagnosis, Differential; Humans; Hyperglycemia; Leucovorin; Male; Rectal Neoplasms; Tegafur; Uracil

Solitary adrenal metastasis of rectal cancer is comparatively rare condition and it is difficult to be diagnosed because it doesn't have any characteristic symptoms. We report a case of this type of adrenal tumor that could be figured out by tumor markers and the analysis of CT scan image. A 67-year-old man visited our department with the right adrenal tumor. He has a past medical history of rectal cancer and a low anterior resection was performed in 2011. After the surgery, he received adjuvant chemotherapy for 6 months. There has been no finding of recurrence or metastasis after chemotherapy. However, his follow-up abdominal CT in 2013 showed the right adrenal tumor which was 23 mm in diameter. Serum CEA level has also increased to 4.1 ng/ml, but there was no abnormal finding with hormonal study. The tumor size and CEA level gradually increased up to 46 mm in size and 10.4 ng/ml during 6 months. Enhanced CT also showed 39% at rate of absolute percentage wash out, which was not the finding of typical functional adrenal tumor. Based on these findings, we diagnosed that the origin of this adrenal tumor should be solitary metastasis of the rectal cancer. For the treatment of surgical procedure, we performed laparoscopic right adrenalectomy. The pathological finding showed adenocarcinoma, the origin of which was the previous rectal cancer. Six months have passed since the surgery, but CEA level still has remained normal range and neither finding of recurrence nor metastasis has been found.

Topics: Adenocarcinoma; Adrenal Gland Neoplasms; Adrenalectomy; Aged; Antineoplastic Combined Chemotherapy Protocols; Colectomy; Fluorouracil; Humans; Leucovorin; Male; Organoplatinum Compounds; Rectal Neoplasms; Recurrence; Tomography, X-Ray Computed

A 60-year-old man who had bloody stools after sigmoid colonoscopy was admitted to our hospital. A digital examination and sigmoid colonoscopy showed a type 2 circular tumor at location Rb with incomplete mobility and tumor hemorrhage, and the result of a biopsy was moderately differentiated adenocarcinoma (tub2). Computed tomography and magnetic resonance imaging suggested a possibility of invasion of the primary rectal tumor to the sacrum. The clinical stage was cT4bN0M0H0P0, cStage Ⅱ, which is generally not treatable by surgery. Sigmoid colostomy was performed, and a central venous port was implanted. After a preoperative treatment consisting of 3 courses of mFOLFOX6 and radiation therapy, the clinical stage changed to ycT2N0M0H0P0, ycStageⅠ. Super-low anterior resection and covering ileostomy were performed 46 days after the preoperative treatment. A pathological examination revealed no residual cancer cells in the primary lesion and lymph node (Grade 3, pCR). The patient has been disease-free for 4 years and 9 months after the operation.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Fluorouracil; Humans; Leucovorin; Magnetic Resonance Imaging; Male; Middle Aged; Organoplatinum Compounds; Rectal Neoplasms; Remission Induction; Tomography, X-Ray Computed

A 48-year-old man with colorectal cancer and right inguinal lymph node metastasis had previously undergone radiotherapy and chemotherapy (uracil/tegafur/leucovorin) after a colostomy in another hospital before being referred to us. Esophagogastroduodenoscopy (EGD) revealed the presence of a gastric metastatic lesion. After three courses of treatment with a modified regimen of leucovorin plus 5-fluorouracil plus oxaliplatin-6 (mFOLFOX6), EGD revealed that the gastric lesion had disappeared; computed tomography revealed that the size of the primary tumor and inguinal lymph node metastasis were markedly reduced. Subsequently, he underwent rectal resection of the primary tumor and continued treatment with mFOLFOX6 in combination with bevacizumab. We reviewed 29 similar cases from the literature, and determined that surgical resection of the tumor and appropriate chemotherapy can lead to long-term survival for patients with gastric metastases from colorectal cancer. Furthermore, positive CK20 and CDX2 expression and negative CK7 expression were useful adjuncts in the immunohistochemical diagnosis of gastric metastases from colorectal adenocarcinoma.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Rectal Neoplasms; Stomach Neoplasms; Tomography, X-Ray Computed

A 64-year-old male with fatigue and icterus was referred to our hospital. Computed tomography(CT)demonstrated multiple liver metastases and colonoscopic examination revealed advanced rectal cancer, which was diagnosed as moderately- differentiated adenocarcinoma without KRAS mutation. His serum total bilirubin level was 15.6 mg/dL. We started combination chemotherapy with 5-fluorouracil, Leucovorin and oxaliplatin(modified FOLFOX6)at a 20% lower than standard dosage for safety. When his bilirubin fell to 2.3 mg/dL after 4 courses of mFOLFOX6, the doses of 5-fluorouracil and oxaliplatin were increased to standard doses, and treatment with bevacizumab of 5 mg/kg every 2 weeks was begun. After another 3 courses of chemotherapy, his bilirubin was normalized to 0.8 mg/dL. No significant toxicity was observed. Combination chemotherapy with mFOLFOX6 plus bevacizumab was effective and feasible in this case of metastatic rectal cancer with icterus due to diffuse liver metastases.

Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Fatal Outcome; Fluorouracil; Humans; Jaundice; Leucovorin; Liver Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Rectal Neoplasms

Two phase III trials of neoadjuvant treatment in T3-4 rectal cancer established that adding chemotherapy (CRT) to radiotherapy (RT) improves pathological complete response (pCR) and local control (LC). We combined trials to assess the clinical benefit of CRT on overall (OS) and progression free survival (PFS) and to explore the surrogacy of pCR and LC.. Individual patient data from European Organisation for Research and Treatment of Cancer (EORTC) 22921 (1011 patients) and FFCD 9203 (756 patients) were pooled. Meta-analysis methodology was used to compare neoadjuvant CRT to RT for OS, PFS LC and distant progression (DP). Weighted linear regression was used to estimate trial-level association (surrogacy R(2)) between treatment effects on candidate surrogate (pCR, LC, DP) and OS.. The median follow-up was 5.6 years. Compared to RT (881 pts), CRT (886 pts) did not prolong OS, DP or PFS. The 5-y OS-rate was 66.3% with CRT versus 65.9% in RT (hazard ratios (HR) = 1.04 {0.88-1.21}). CRT significantly improved LC (HR = 0.54, 95%confidence interval (CI): 0.41-0.72). PFS was validated as surrogate for OS with R(2) = 0.88. Neoadjuvant treatment effects on LC (R(2) = 0.17) or DP (R(2) = 0.31) did not predict effects on OS.. Preoperative CRT does not prolong OS or PFS. pCR or LC do not qualify as surrogate for PFS or OS while PFS is surrogate. Phase III trials should use OS or PFS as primary endpoint.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Clinical Trials, Phase III as Topic; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Rectal Neoplasms; Young Adult

As pharmacokinetics in patients undergoing haemodialysis is different from patients with normal renal function, it remains unclear whether chemotherapy can be performed safely for patients with haemodialysis as well as those who have normal renal function. Here, we report a case with recurrence of rectal cancer who received FOLFIRI with bevacizumab chemotherapy under haemodialysis, and obtained good tumor control. A 47-year-old woman had undergone haemodialysis for 10 years due to chronic renal failure. At 45 years of age, she received abdominoperineal resection due to rectal cancer (pStage II). Four months after the surgery, liver metastasis was found, for which partial resection of the liver and adjuvant chemotherapy [UFT (400 mg/body)/UZEL (75 mg/body)] were performed. Eighteen months after the liver resection, multiple lung metastases were found. Therefore, intensive chemotherapy using FOLFIRI (CPT-11: 90 mg/m2) with bevacizumab (2.5 mg/m2) was performed. Severe neutropenia (grade 3, 4), but not non-hematologic adverse events such as diarrhea and bevacizumab-specific adverse events, was observed. As she did not recover easily from neutropenia in spite of treatment with G-CSF, a dose reduction of the FOLFIRI regimen was gradually performed. Although chemotherapy was conducted approximately monthly, the tumor response reflected a stable disease 8 months after 8 courses of chemotherapy. We suggest that it is important to investigate the pharmacokinetics of toxic agents such as CPT-11, (SN38) for dose modification, and for the safe and continuous chemotherapy of patients receiving haemodialysis.

Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Female; Fluorouracil; Humans; Kidney Failure, Chronic; Leucovorin; Liver Neoplasms; Lung Neoplasms; Middle Aged; Rectal Neoplasms; Recurrence

Topics: Adenocarcinoma; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Female; Fluorouracil; Humans; Leucovorin; Organoplatinum Compounds; Oxaliplatin; Purpura, Thrombotic Thrombocytopenic; Rectal Neoplasms

A 75-year-old man with advanced undifferentiated rectal cancer, diagnosed by endoscopic biopsy, underwent preoperative short-term chemoradiotherapy (whole pelvis, 4 Gy × 5 day with UFT 400 mg/day × 7 day). Tumor size and lymph node swellings were reduced after radiation therapy. Down-staging was achieved from cT3, cN2, cStage III b to cT3, cN1, cStage III a. A curative low anterior resection with D3 lymphadenectomy including lateral lymph node dissection, was performed 4 weeks after the completion of chemoradiotherapy. Pathological findings of resected specimen showed undifferentiated carcinoma with regional lymph node involvement (pT2, pN1, pStage III a). The histological change in response to chemoradiation was evaluated as Grade 2. The postoperative course was uneventful and postoperative adjuvant chemotherapy (UFT+Uzel) was performed for six months (5 courses). No sign of recurrence has been found until 51 months after the operation. Undifferentiated rectal cancer is a rare condition with extremely poor prognosis according to the Japanese literature. Nine cases have been reported so far with only one long-term survivor. This combination of preoperative short-term chemoradiotherapy and adjuvant chemotherapy, which is one of the standard strategies for advanced rectal cancer in Western countries, but not common in Japan, may be a promising option for treatment of undifferentiated rectal cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cell Differentiation; Chemotherapy, Adjuvant; Humans; Leucovorin; Male; Neoplasm Staging; Rectal Neoplasms; Tegafur; Time Factors; Uracil

FOLFOX/bevacizumab has been shown to be a promising chemotherapeutic regimen for advanced or metastatic colorectral cancer. We reported a case of intestinal lung diseases occurring in association with the use of this combination chemotherapy. The patient presented here is a 71-year-old man with lung metastasis of rectal cancer who was treated with FOLFOX4/ bevacizumab. He complained of high fever in the eleventh course of a FOLFOX4/bevacizumab regimen. Chemotherapy was stopped. But fourteen days after, he suffered from dyspnea and soon went into respiratory failure of WHO grade 3 with severe hypoxemia. He was diagnosed with interstitial pneumonitis. Corticosteroid therapy consisting of metylprednisolone(1 g/day) for tree days was significantly effective in treatment of respiratory failure. Drug-induced interstitial pneumonitis was suspected from chest X-ray and CT. We performed DLST of oxaliplatin, l-levofolinate, 5-FU and bevacizumab for him. He was positive for oxaliplatin and l-levofolinate and 5-FU, and negative for bevacizumab. Interstitial pneumonitis induced by FOLFOX/bevacizumab chemotherapy is rare, but six patients had developed, one of whom died in post-marketing surveillance. The possibility of interstitial pneumonitis should always be considered when a patient presents with a respiratory disorder while undergoing systemic chemotherapy.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Leucovorin; Lung Diseases, Interstitial; Lung Neoplasms; Male; Organoplatinum Compounds; Rectal Neoplasms; Tomography, X-Ray Computed

A 74-year-old female had metastatic left inguinal lymph nodes 20 months after rectal amputation for cancer, and an attempt to adapt chemotherapy of mFOLFOX6/bevacizumab was made after resection of the nodes. She felt nausea 2 days and continued 1 week after starting chemotherapy. Then, an endoscopic examination revealed both active gastric and duodenal ulcers. Clipping and proton pump inhibitor medication was started. The ulcers healed to the healing stage at 18 days and to the scar stage at 28 days. Gastrointestinal complications often occur after chemotherapy, but severe ulcers are rarely reported. The chemotherapy included anti-VEGF antibody, but the ulcers have healed back to normal.

Topics: Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Duodenal Ulcer; Female; Fluorouracil; Humans; Leucovorin; Organoplatinum Compounds; Rectal Neoplasms; Stomach Ulcer

Protracted preoperative radiochemotherapy with a 5-FU-based scheme, or a short course of preoperative radiotherapy without chemotherapy, are the standard neoadjuvant treatments for resectable stage II-III rectal cancer. Local failure rates are low and reproducible, between 6 and 15% when followed with a "Total Mesorectal Excision". Nevertheless, the therapeutic strategy needs to be improved: distant metastatic recurrence rates remain stable around 30 to 35%, while both sphincter and sexual sequels are still significant. The aim of the present paper was to analyse the ongoing trials listed on the following search engines: the Institut National du Cancer in France, the National Cancer Institute and the National Institute of Health in the United States, and the major cooperative groups. Keywords for the search were: "rectal cancer", "preoperative radiotherapy", "phase II-III", "preoperative chemotherapy", "adjuvant chemotherapy" and "surgery". Twenty-three trials were selected and classified in different groups, each of them addressing a question of strategy: (1) place of adjuvant chemotherapy; (2) optimization of preoperative radiotherapy; (3) evaluation of new radiosensitization protocols and/or neoadjuvant chemotherapy; (4) optimization of techniques and timing of surgery; (5) place of radiotherapy for non resectable or metastatic tumors.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Capecitabine; Cetuximab; Chemotherapy, Adjuvant; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Combined Modality Therapy; Deoxycytidine; Fluorouracil; Forecasting; Humans; Irinotecan; Leucovorin; Multicenter Studies as Topic; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaliplatin; Radiation-Sensitizing Agents; Radiotherapy, Conformal; Randomized Controlled Trials as Topic; Rectal Neoplasms; Time Factors; Treatment Outcome

The results of the recently published large European randomised study in rectal cancer (European Organisation for Research and Treatment of Cancer 22921 trial) do not support current guidelines recommending postoperative chemotherapy for patients who have previously undergone preoperative radiochemotherapy or radiotherapy [radio(chemo)therapy]. To evaluate this discrepancy further, a systematic review of relevant randomised trials was undertaken.. A systematic literature search was carried out in order to identify randomised studies exploring adjuvant chemotherapy against observation in patients with rectal cancer previously treated with preoperative radio(chemo)therapy.. A statistically significant benefit of adjuvant chemotherapy was not found in any of the four relevant randomised trials. Non-protocolised subgroup analysis of one study indicated a beneficial effect of adjuvant chemotherapy for high rectal tumours and for patients downstaged to ypT0-2N0 but no effect for low-lying rectal tumours. However, the body of evidence indicates that patients downstaged after radio(chemo)therapy to ypT0-2N0 disease are not candidates for testing adjuvant chemotherapy in future trials due to the considerable over-treatment anticipated by this manoeuvre.. To resolve the issue in question, a meta-analysis of relevant studies is required, and new trials should be launched to explore new drug combinations against observation. Currently, delivery of adjuvant chemotherapy in patients undergoing preoperative radio(chemo)therapy is not evidence based.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Fluorouracil; Humans; Leucovorin; Neoadjuvant Therapy; Prognosis; Radiotherapy, Adjuvant; Randomized Controlled Trials as Topic; Rectal Neoplasms

A 45-year-old woman, complaining of back pain and bloody stool was given a diagnosis of poorly differentiated adenocarcinoma of the rectum with disseminated carcinomatosis to bone marrow and disseminated intravascular coagulation syndrome (DIC). We started chemotherapy using mFOLFOX-6 with simultaneous DIC treatment. After we confirmed that DIC had improved following 2 courses of mFOLFOX-6, bevacizumab was added to mFOLFOX-6. Laboratory studies revealed a serum CEA level of 314.4ng/ml, which improved to 4.6ng/ml after a total of 6 courses of chemotherapy. Colonoscopy findings showed almost normal rectal mucosa after a total of 10 courses of chemotherapy. Outpatient treatment was started after 5 courses of chemotherapy, and was continuing according to schedule at 7 months from the onset of this disease.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Bone Marrow Neoplasms; Carcinoma; Female; Fluorouracil; Humans; Leucovorin; Middle Aged; Organoplatinum Compounds; Rectal Neoplasms

Topics: Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemotherapy, Adjuvant; Chromosomal Instability; Colonic Neoplasms; Deoxycytidine; Fluorouracil; Humans; Leucovorin; Microsatellite Instability; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Oxaloacetates; Prognosis; Rectal Neoplasms; Risk Factors

Neoadjuvant radiochemotherapy has become established treatment for rectal cancer. It is indicated when primary R0 resection is not an option, in cases of higher risk of locoregional relapse following surgical treatment alone, and when initially impossible conservation of the anal sphincter becomes possible in conjunction with neoadjuvant radiochemotherapy. The indication for radiochemotherapy in the upper third of the rectum is still controversial. Reevaluation of the tumor situation following neoadjuvant treatment is necessary before decisions on operative strategy. Modern imaging techniques are limited in this respect, as they hardly allow differentiation between living tumor tissue and lesions. In case of doubt clarity is possible only through surgical exploration, taking R1 resection into account. Overall the recognition of lymph node metastasis is not a sufficient indicator of local relapse. The frequency of postoperative complications following neoadjuvant radiochemotherapy is independent of the operative method. The effect of neoadjuvant radiochemotherapy on long-term survival and formation of distant metastases is still not clarified. Current studies seek clarification through the use of new chemotherapies and modified treatment regimes. Further, the correct time interval between the end of neoadjuvant radiochemotherapy and the following surgical therapy has yet to be determined. This applies also to the management of patients following complete remission.

Topics: Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Dose Fractionation, Radiation; Fluorouracil; Humans; Leucovorin; Lymphatic Metastasis; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Rectal Neoplasms; Rectum; Survival Rate

Locally advanced rectal adenocarcinoma is treated by combined-modality therapy, which consists of surgery, chemotherapy, and radiation therapy. A series of randomized trials established a preferred treatment sequence of preoperative radiation therapy and 5-fluorouracil(5-FU)-based chemotherapy, total mesorectal excision, and adjuvant 5-FU-based chemotherapy for patients with stage II/III disease. Capecitabine is an oral prodrug of 5-FU that has potential advantages compared with intravenous 5-FU, including ease of administration and potentially increased therapeutic effect. Capecitabine is converted by a 3-step enzymatic process; the last step involves the enzyme thymidine phosphorylase, which is overexpressed in tumor tissues and is stimulated by concurrent radiation therapy. Over the past 5 years, several phase I/II trials of capecitabine-based therapy were reported. This review discusses the evolution of combined-modality therapy for rectal cancer with specific attention given to the use of capecitabine in conjunction with radiation therapy.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemotherapy, Adjuvant; Deoxycytidine; Fluorouracil; Humans; Leucovorin; Prognosis; Radiotherapy, Adjuvant; Rectal Neoplasms; Thymidine Phosphorylase; Vitamin B Complex

Chemotherapy that targets metastatic colorectal cancer originally developed in Europe and the US, and was introduced to Japan in April, 2005, where it has since headed toward full scale clinical applications. This event created an opportunity to re-evaluate the role of postoperative adjuvant chemotherapy in Japan. In Europe and the US, adjuvant therapy has centered on the intravenous administration of leucovorin/fluorouracil, while in Japan, it has been long-term continuous administration of oral fluoropyrimidine preparations. Despite this difference in historical background,guidelines created in 2005 recommend both LV/5-FU and LV/UFT regimens and there has been increased application of evidence-based adjuvant chemotherapy. The benefits of postoperative adjuvant chemotherapy in stage II and III (high risk of recurrence) colorectal cancer patients have also come to be recognized. Examination of a new survey of 100 medical specialists on the current state of adjuvant chemotherapy for colorectal cancer in Japanese clinical settings revealed that for stage III patients, there is a tendency to choose treatment based on evidence gathered from both home and abroad. In contrast, a solid majority (60%) of stage II patients are treated exclusively with oral fluoropyrimidine despite a lack of, or limited evidence of efficacy. At the same time, half of the physicians who treated stage II patients with adjuvant chemotherapy initially attempted to identify those with a high risk of cancer recurrence and treat them accordingly; which was a breakthrough in the clinical treatment approach. While ongoing comparative Japanese clinical studies that use adjuvant chemotherapy for the treatment of colorectal cancer were noted, consideration was also given to the desired future direction clinical research should take.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Colonic Neoplasms; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Europe; Evidence-Based Medicine; Fluorouracil; Humans; Irinotecan; Japan; Leucovorin; Neoplasm Staging; Oxonic Acid; Practice Guidelines as Topic; Rectal Neoplasms; Tegafur; United States; Uracil

Angiogenesis is one of the hallmarks of cancer. Among the identified angiogenic factors, vascular endothelial growth factor (VEGF) is a crucial regulator of angiogenesis in normal and malignant tissue. Increased expression of VEGF has been detected in most tumors of humans, and it is associated with increased risks of recurrence, metastasis, and death. Bevacizumab (Avastin), a recombinant humanized monoclonal antibody targeting VEGF, has been evaluated in various solid tumors. Some pivotal phase III trials demonstrated that the addition of bevacizumab to conventional chemotherapy showed a survival benefit with acceptable toxicity. The United States Food and Drug Administration approved the use of bevacizumab for patients with unresectable colorectal cancer and unresectable non-squamous, non small cell lung cancer. In April 2007, the Japanese Ministry of Health, Labour and Welfare approved bevacizumab for patients with unresectable colorectal cancer. The usage of bevacizumab will be stipulated in combination with 5-fluorouracil containing chemotherapy at a dose of 5 mg/kg or 10 mg/kg given every 14 days. To know its efficacy and safety of bevacizumab is necessary for Japanese patients in the clinical practice.

Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Breast Neoplasms; Camptothecin; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Clinical Trials, Phase III as Topic; Colonic Neoplasms; Drug Administration Schedule; Drug Approval; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Lung Neoplasms; Male; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms; Vascular Endothelial Growth Factor A

Surgery alone is no longer appropriate to the treatment of T3-T4 resecable rectal cancer. Preoperative chemoradiotherapy has recently been approved as the new standard treatment. This approach improves local control with local failure rate raranging now around 6-8%. However, it does not impact on overall survival. It becomes urgent to develop new concepts and a basic research in the understanding of the biological mechanisms that may explain the resistance of the micrometastatic process.

Topics: Antimetabolites, Antineoplastic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Combined Modality Therapy; Drug Therapy, Combination; Female; Fluorouracil; Humans; Leucovorin; Male; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasm Staging; Preoperative Care; Prognosis; Radiotherapy Dosage; Randomized Controlled Trials as Topic; Rectal Neoplasms; Rectum; Tomography, X-Ray Computed; Vitamin B Complex

Patients diagnosed with rectal cancer should undergo locoregional staging with transrectal endoscopic ultrasound (EUS) or surface coil array MRI of the pelvis if that technique is available. Patients thought to have more than very early stage (T1 or T2) disease should undergo abdominal imaging as well by CT or MRI, and chest imaging with either CXR or preferably CT. The care of rectal cancer patients should be coordinated amongst an experienced multidisciplinary team to maximize the chance of cure and to minimize both local recurrence and complications of therapy. For patients with very early stage disease (T1N0 or T2N0), local resection with or without chemoradiation may be adequate therapy, but these patients must be selected carefully and should be without any poor prognostic factors. For the majority of patients with T3N0 or greater rectal cancer, standard therapy consists of neoadjuvant continuous 5-FU and radiation followed by surgery and further chemotherapy (either with 5-FU, capecitabine, or FOLFOX). The use of capecitabine, irinotecan, and oxaliplatin during radiotherapy shows promise, but remains investigational pending results of phase III studies. Neoadjuvant therapy is preferred because it decreases local recurrence and appears to result in improved postoperative bowel function in comparison with postoperative therapy. Select patients with high (>10 cm from the anal verge) uT3N0 tumors may be at sufficiently low risk of local recurrence to justify omission of radiotherapy. Patients who experience pathologic complete response to radiotherapy should still receive postoperative adjuvant chemotherapy to reduce systemic recurrence risk until data demonstrate that this is not necessary. Patients with stage IV rectal cancer may still require local therapy with radiation, surgery, or both; however, care should be taken in these patients that chemotherapy is not excessively delayed as this is the one modality in this case that can result in improved survival.

Topics: Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemotherapy, Adjuvant; Deoxycytidine; Endosonography; Fluorouracil; Humans; Leucovorin; Magnetic Resonance Imaging; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Radiotherapy, Adjuvant; Rectal Neoplasms; Tomography, Emission-Computed

Irinotecan (CPT-11) plus 5-fluorouracil (5-FU) and Leucovorin (LV) became the standard first-line chemotherapy for colorectal cancer in the U.S. and Europe in 2000, largely owing to the results of controlled randomized phase III trials of 5-FU/LV with or without CPT-11. One of the regimens for CPT-11 plus infusional 5-FU/LV therapy is the FOLFIRI regimen. This regimen consists of CPT-11 180 mg/m(2) as a 90-min infusion on day 1 and l-LV 200 mg/m(2) as a 2-h infusion during CPT-11, immediately followed by a bolus dose of 5-FU 400 mg/m(2) and a 46-h continuous infusion of 2,400 mg/m(2) every 2 weeks. FOLFIRI, as well as oxaliplatin/5-FU/LV therapy (FOLFOX), is an internationally accepted standard chemotherapy for metastatic colorectal cancer. Safe use of this effective regimen requires adequate supportive therapy in Japan, as well as in Western countries.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Clinical Trials, Phase III as Topic; Colonic Neoplasms; Drug Administration Schedule; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Randomized Controlled Trials as Topic; Rectal Neoplasms

Formerly the treatment of gastrointestinal cancers was exclusively surgical. Though the results were improved by increased radicality, the real progress was achieved by the introduction of multimodal therapy, particularly by the neoadjuvant concept. The basic prerequisite for neoadjuvant treatment is precise staging and risk assessment. According to staging patients can be divided into three categories: (1) Early cancers, confined to the mucosal and submucosal layers, are approached with primary surgery. (2) Systemically metastasized tumors receive merely palliative treatment. (3) Locally advanced cancers are treated by neoadjuvant therapy. Due to neoadjuvant treatment the tumor can be downsized (or downstaged) in some patients. These are the responders benefiting from the therapy, because of the increased RO-resection rate, decreased recurrence rate and improved survival. The non-responders, by contrast have poor prognosis. Neoadjuvant treatment considerably improved the chance for cure for patients with gastrointestinal cancers, thus this method became an evidence based treatment for locally advanced gastrointestinal cancers.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Chemotherapy, Adjuvant; Cisplatin; Epirubicin; Esophageal Neoplasms; Female; Fluorouracil; Gastrointestinal Neoplasms; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Radiotherapy Dosage; Radiotherapy, Adjuvant; Rectal Neoplasms; Remission Induction; Retrospective Studies; Stomach Neoplasms; Survival Analysis; Treatment Outcome

Topics: Antineoplastic Combined Chemotherapy Protocols; Clinical Trials, Phase II as Topic; Combined Modality Therapy; Disease-Free Survival; Drug Combinations; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Preoperative Care; Rectal Neoplasms; Survival Rate; Tegafur; Uracil

We relate 2 cases reports about rectal cancer and pregnancy. This association is rare but is a real problem of management because diagnosis is done latly and it mate have incompatibility between treatments and pregnancy. A medical bibliography has been done, to define the best medical procedure in function of the disease staging and the pregnancy term. It shows that a multi disciplinary decision must be done, which take into consideration the choice of the obstetricals, pediatricians, surgeons, and oncologists, but also the patient's choice.

Topics: Adenocarcinoma; Adult; Antineoplastic Agents; Case Management; Cesarean Section; Chemotherapy, Adjuvant; Combined Modality Therapy; Diagnostic Errors; Female; Fluorouracil; Gastrointestinal Hemorrhage; Hemorrhoids; Humans; Infant, Newborn; Leucovorin; Lymphatic Metastasis; Pregnancy; Pregnancy Complications, Neoplastic; Prognosis; Rectal Neoplasms; Rectum; Risk Factors

The progress and role of adjuvant therapy for resectable colorectal cancers are reviewed herein. 5-FU/leucovorin is considered the standard treatment in the postoperative adjuvant chemotherapy for Dukes'C colon cancer. The oral 5-FU prodrugs, such as UFT and capecitabine, will replace 5-FU infusion in the adjuvant chemotherapy in the near future. In Dukes'B colon cancer, the results of postoperative adjuvant chemotherapy are controversial. Many randomized trials in the USA and Europe have demonstrated that pre- or postoperative radiation therapy for rectal cancer decreases local recurrences but has no additional benefit on survival compared with 5-FU-based adjuvant chemotherapy. Adjuvant radiation therapy for rectal cancer is not widely used in Japan, while chemotherapy is considered the adjuvant treatment of choice. The local recurrences of rectal cancer is a surgeon-related phenomenon: the surgical technique used and the skill of the surgeon are major factors influencing outcome.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colorectal Neoplasms; Drug Administration Schedule; Fluorouracil; Humans; Leucovorin; Mitomycin; Radiotherapy, Adjuvant; Rectal Neoplasms; Tegafur; Uracil

Preclinical evidence of a schedule-dependent synergism between raltitrexed and 5-fluorouracil (5-FU) has prompted clinical studies of this combination. We review the main preclinical and clinical results of raltitrexed/5-FU-based combination chemotherapy regimens in anticancer therapy. Promising results include: response rates of 25 and 23% with combinations of raltitrexed/5-FU/levofolinic acid (LFA) as first-line treatment and oxaliplatin/raltitrexed/5-FU/LFA as second-line treatment of metastatic colorectal cancer, respectively; and a 67% response rate in a phase I study of cisplatin/raltitrexed/5-FU/LFA as first-line treatment of advanced head and neck cancer, including a 100% response rate at the recommended dose. These combinations were well tolerated, with neutropenia as the main dose-limiting toxicity, allowing the drugs to be combined at the doses used in monotherapy. These results suggest a role for raltitrexed within combination regimens in colorectal cancer therapy, as well as other tumors such as head and neck cancer. A further potential application of raltitrexed in combination therapies is within multidisciplinary chemo-radiotherapy strategies, mainly in rectal cancer. Phase II studies are planned/ongoing to investigate these interesting possibilities.

Topics: Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Colorectal Neoplasms; Fluorouracil; Head and Neck Neoplasms; Humans; Leucovorin; Neoplasm Metastasis; Neoplasms; Organoplatinum Compounds; Oxaliplatin; Quinazolines; Rectal Neoplasms; Thiophenes

Capecitabine is a novel fluoropyrimidine carbamate, orally administered and rationally designed to undergo tumor-selective activation. Some studies have been proven it to be safe for outpatient treatment and to have significant antitumor activity in colorectal and breast cancer patients. Randomized trials of patients with advanced colorectal cancer using capecitabine versus Leucovorin (LV).5-FU were studied in two groups. Capecitabine results in both a higher response rate and a more favorable toxicity profile than LV.5-FU. In women aged 55 years or more with breast cancer, capecitabine showed at least comparable efficacy to CMF combination therapy. Capecitabine offers a new effective oral treatment option as a single agent for patients with advanced colorectal or breast cancer.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Capecitabine; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Colonic Neoplasms; Deoxycytidine; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Randomized Controlled Trials as Topic; Rectal Neoplasms

Although the liver is the most common site of metastatic disease from a variety of tumor types, isolated hepatic metastases most commonly occur from colorectal cancer and, less frequently, from neuroendocrine tumors, gastrointestinal sarcoma, ocular melanoma, and others. Complete evaluation of the extent of metastatic disease, both intrahepatically and extrahepatically, is important before considering treatment options. Based on a preponderance of uncontrolled studies for hepatic metastatic colorectal carcinoma, surgical resection offers the only potential for cure of selected patients with completely resected disease, with 5-year survival rates of 25% to 46%. Systemic and hepatic arterial infusion chemotherapy may be useful treatment options in patients with unresectable disease and possibly as an adjuvant treatment after liver resection. Other techniques of local tumor ablation, including cryotherapy and radiofrequency ablation, although promising, remain unproved. Management of hepatic metastases from neuroendocrine tumors and other noncolorectal primary tumors should be individualized based on the patient's clinical course, extent of disease, and symptoms.

Topics: Antidotes; Antimetabolites, Antineoplastic; Antineoplastic Agents; Colonic Neoplasms; Fluorouracil; Hepatectomy; Humans; Infusions, Intra-Arterial; Leucovorin; Liver Neoplasms; Neoplasm Recurrence, Local; Neuroendocrine Tumors; Rectal Neoplasms; Treatment Outcome

The majority of colorectal neoplasms diagnosed are adenocarcinomas. Other histologies such as squamous, adenosquamous, carcinoid tumors, or lymphoid tumors are occasionally identified. Given the rarity of squamous-cell tumors, it is very difficult to study their natural course and response to therapy. An attempt is made to describe the frequency, anatomic location, and response to therapy with a review of the literature.. From the Cancer Registry at the University of Missouri-Columbia Ellis Fischel Cancer Center, tumors of the colon identified above the dentate line were selected for chart review. Data were extracted from cases between the years 1940 and 1996. The key terms used to identify cases were epidermoid, squamous cell, and cancer of the rectum or colon. Using this approach, forty patients were identified and each record was reviewed.. The majority of these cases were anal cancers with proximal extension into the rectum and were excluded. Of 4,561 cases of epithelial colon and rectal cancers identified, only one additional case of squamous-cell cancer could be verified. In this report we describe a patient with a primary squamous-cell carcinoma of the sigmoid colon with metastatic disease to the liver at diagnosis who responded to systemic chemotherapy. We believe this to be the first reported case of this rare tumor type in which the patient's tumor responded to systemic chemotherapy. Two cases with a thorough review of literature are presented.. Primary squamous-cell carcinoma of the colon is a rare malignancy of unknown cause and pathogenesis. Metastatic tumors to the colon should be ruled out in all cases before therapy. Early detection and surgery remain the main therapeutic options, but as presented in our case, response to chemotherapy in advanced disease is encouraging.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Anus Neoplasms; Carcinoma, Squamous Cell; Cisplatin; Colonic Neoplasms; Female; Fluorouracil; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Leucovorin; Male; Middle Aged; Rectal Neoplasms

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colonic Neoplasms; Fluorouracil; Humans; Leucovorin; Palliative Care; Prognosis; Quality of Life; Rectal Neoplasms

5-Fluorouracil (5-FU) has been available for over 40 years and has been used in a wide variety of different regimens for the treatment of advanced colorectal cancer, a malignancy with a poor prognosis that is common in industrialized countries. However, despite numerous clinical trials in which 5-FU has been used alone and in combination with a variety of modulating agents [chiefly leucovorin (LV)], and has been administered by bolus injection and i.v. infusion, the optimal regimen for the management of advanced colorectal cancer remains unclear, and there are notable national and international variations in clinical practice. The toxicity of 5-FU also remains an obstacle to the achievement of overall clinical benefit in many patients. The introduction of novel chemotherapeutic agents may make it necessary to reassess the place of 5-FU in the treatment of advanced colorectal cancer. This article debates these issues with a review of clinical trials of 5-FU, and concludes that the future lies in the utilization of novel and established agents in combinations that may significantly improve outcomes, rather than in continuing experimentation with various schedules of 5-FU and LV.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Humans; Infusions, Intravenous; Injections, Intravenous; Leucovorin; Rectal Neoplasms

Systemic palliative chemotherapy is usually regarded as ineffective in disseminated colorectal cancer, and the risk of toxic adverse effects is often considered a contraindication, as many patients are old and cannot be offered curative treatment. Randomized trials during the last decade have shown, however, that an effect on both survival and quality of life can be expected. Only casuistic reports of total remission have been published but a partial tumour response can be expected in 20-50% of patients. Toxicity is related to palliative chemotherapy and accelerated with old age (> 70 years). When disseminated colorectal cancer is diagnosed the possibility of palliative chemotherapy should be conferred with an oncologist.

Topics: Age Factors; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Fluorouracil; Humans; Leucovorin; Meta-Analysis as Topic; Palliative Care; Quality of Life; Randomized Controlled Trials as Topic; Rectal Neoplasms

Evaluation of surgery and multidisciplinary treatment for colorectal cancer was performed based on the review of the results of clinical trials. Although most improvement in prognosis for colorectal cancer patients was obtained by the development of surgical techniques until the mid-70's, further extended surgery could not have demonstrated the obvious improvement in survival after the 80's. In this regard, various multidisciplinary treatments were evaluated by a meta-analysis of clinical trials. Among those modalities, preoperative irradiation for rectal cancer, postoperative adjuvant chemotherapy for resected colorectal cancer and biochemical modulation of 5-fluorouracil by methotrexate or leucovorin for advanced colorectal cancers proved to be significantly effective for improvement of prognosis. Clinical trials of immunochemotherapy using either levamisole or PSK for resected colorectal cancers, a trial of hepatic artery infusion for liver metastasis, and a trial of an adjuvant monoclonal antibody treatment, were also reported to demonstrate significant effects. For further progress in multidisciplinary treatment for colorectal cancers, standardization of the appropriate surgical technique for each stage of the disease is much anticipated.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colonic Neoplasms; Combined Modality Therapy; Fluorouracil; Humans; Immunologic Factors; Leucovorin; Meta-Analysis as Topic; Rectal Neoplasms; Survival Rate

Since its introduction in 1953, 5-fluorouracil based chemotherapy remained the standard treatment in advanced colorectal cancer. Continuous infusion or biochemical modulation by folinic acid enhanced the therapeutic efficacy of this agent. Quality of life is limited by the toxicity of these regimens as well as by the frequent visits to the hospital during each cycle. Raltitrexed, a thymidylate synthase inhibitor, offers similar antitumoral activity together with a tolerability in comparison to standard 5-fluorouracil based chemotherapy and its simple dosage schedule also contributes to better quality of life. New chemotherapeutic agents are currently in development for the treatment of patients refractory to 5-fluorouracil. Irinotecan and oxaliplatin demonstrate promising activity.

Topics: Antidotes; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Camptothecin; Colonic Neoplasms; Enzyme Inhibitors; Fluorouracil; Hospitalization; Humans; Irinotecan; Leucovorin; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Palliative Care; Quality of Life; Quinazolines; Rectal Neoplasms; Thiophenes; Thymidylate Synthase; Topoisomerase I Inhibitors

Induction, or preoperative therapy for rectal carcinoma, is a controversial topic which appears to have clinical utility in a number of distinct settings that range from early stage to locally advanced disease. Common to all treatment scenarios is the intent of reducing the likelihood of recurrence in the pelvis following surgery. An additional and evolving role is a reduction in the extent of surgery following a complete or partial clinical response to the induction regimen. While radiation as a single modality can lead to downstaging and, perhaps, a reduction in local recurrence, combined modality with 5-fluorouracil (5-FU) and radiation appears to have a greater therapeutic benefit that may be further enhanced by the administration of leucovorin.

Topics: Antidotes; Antimetabolites, Antineoplastic; Carcinoma; Combined Modality Therapy; Fluorouracil; Humans; Leucovorin; Neoplasm Staging; Preoperative Care; Rectal Neoplasms

Topics: Chemotherapy, Adjuvant; Colorectal Neoplasms; Combined Modality Therapy; Humans; Immunotherapy; Leucovorin; Levamisole; Randomized Controlled Trials as Topic; Rectal Neoplasms

Approximately 141,000 patients will develop colorectal cancer each year and 45% will have positive lymph nodes, one of the most significant predictors of survival. Now there is evidence that systemic chemotherapy with fluorouracil (FU) and leucovorin, levamisole, or FU and leucovorin with decrease recurrence and increase survival for patients with Dukes' C colon cancer. In patients with Dukes' B or C rectal cancer, combined radiation and FU increase survival and decrease local and distal recurrence.

Topics: Adjuvants, Immunologic; Antidotes; Antimetabolites, Antineoplastic; Antineoplastic Agents; Chemotherapy, Adjuvant; Clinical Trials as Topic; Colonic Neoplasms; Fluorouracil; Forecasting; Humans; Infusions, Intravenous; Leucovorin; Levamisole; Lymph Nodes; Lymphatic Metastasis; Neoplasm Recurrence, Local; Portal Vein; Prognosis; Radiotherapy, Adjuvant; Rectal Neoplasms; Survival Rate

Standard adjuvant therapy for transmural (T3) and/or node-positive rectal cancer is pelvic radiation therapy plus fluorouracil (5-FU)-based chemotherapy. Randomized trials are in progress to help determine the ideal chemotherapeutic agents and their optimal routes of administration in this setting, as well as to compare the efficacy and functional results of the pre- and postoperative bolus 5-FU/leucovorin combined-modality therapy approaches. New phase I trials will determine the recommended doses of tegafur and uracil (UFT) with oral leucovorin plus pre- or postoperative radiation therapy.

Topics: Antidotes; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Drug Combinations; Fluorouracil; Forecasting; Humans; Leucovorin; Radiotherapy, Adjuvant; Randomized Controlled Trials as Topic; Rectal Neoplasms; Tegafur; Uracil

Topics: Adult; Age Factors; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Male; Neoplasm Metastasis; Neoplasm Recurrence, Local; Preoperative Care; Quality of Life; Radiotherapy Dosage; Radiotherapy, Adjuvant; Rectal Neoplasms; Risk Factors; Semustine; Sex Factors; Vincristine

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colonic Neoplasms; Fluorouracil; Humans; Immunotherapy; Infusions, Intravenous; Leucovorin; Levamisole; Liver Neoplasms; Neoplasm Staging; Portal Vein; Radiotherapy, Adjuvant; Randomized Controlled Trials as Topic; Rectal Neoplasms; Treatment Failure

An important advance in cancer treatment has been made in recent years with the finding that adjuvant therapy can significantly improve the survival of patients with colorectal cancer. In patients with resected lymph node-positive colon carcinomas (TNM stage 3), adjuvant 5-fluorouracil and levamisole produced an unequivocal survival advantage that established this combination as the standard of clinical practice. Given that biochemical modulation of fluorouracil by leucovorin can increase response rates in advanced disease, this combination is undergoing evaluation as an adjuvant treatment. Preliminary results indicate that 5-fluorouracil and leucovorin are effective in reducing disease relapse; however, the effect of this regimen on patient survival rates awaits extended follow-up. In the treatment of stages 2 and 3 rectal cancer, significant reductions in local recurrence and death rates have been achieved with the combination of 5-fluorouracil and radiation therapy. Immunologic approaches and newer chemotherapeutic agents may further improve patient outcome and are under investigation, as are efforts to reduce the toxic effects of cancer chemotherapy. Increased understanding of the biology of these diseases is likely to yield prognostic markers capable of identifying subgroups of earlier stage patients at high risk of disease relapse who may also benefit from adjuvant therapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colonic Neoplasms; Combined Modality Therapy; Fluorouracil; Humans; Immunotherapy; Leucovorin; Levamisole; Lymphatic Metastasis; Prognosis; Radiotherapy, Adjuvant; Rectal Neoplasms

The encouraging results achieved with adjuvant postoperative combined modality therapy in patients with resectable rectal cancer has prompted an increased interest in preoperative combined modality therapy. Based on the potential of such regimens to deliver higher chemotherapy doses, enhance downstaging, and decrease acute toxicity in patients with unresectable disease, this approach is attractive in patients with resectable rectal cancer. Randomized trials of preoperative vs postoperative combined modality therapy using combinations of bolus fluorouracil and leucovorin are in progress.

Topics: Combined Modality Therapy; Fluorouracil; Humans; Leucovorin; Randomized Controlled Trials as Topic; Rectal Neoplasms

Recent advances have been made with the publication of the results of GITSG and NCCTG trials, which demonstrated the significant improvement of survival by combined postoperative radiochemotherapy protocols for Stage II and III rectal cancer. These data show that systemic chemotherapy has a decisive role to play in this policy. Some of the advantages of preoperative irradiation compared with postoperative radiation therapy consist of the improvement of resectability of T4 tumors and the anal preservation for low-lying cancers. These data suggest that preoperative chemoradiotherapy should be applied not only to T4 tumors but also to all T3 tumors even when the transrectal extension is limited. The most usual protocol combines 5-fluorouracil (300-350 mg/m2/day) and leucovorin (20 mg/m2/day) for 5 days, followed by radiation therapy (30-35 Gy in 10 fractions within 12-15 days), with surgery taking place 4 to 8 weeks later, after the tumor has been restaged. Systemic therapy is continued for four more months. T2 cancers should not be excluded from the benefit of preoperative irradiation.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Drug Administration Schedule; Fluorouracil; Humans; Leucovorin; Preoperative Care; Radiotherapy Dosage; Rectal Neoplasms

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Aspartic Acid; Colonic Neoplasms; Fluorouracil; Humans; Interferons; Leucovorin; Methotrexate; Neoplasm Metastasis; Phosphonoacetic Acid; Rectal Neoplasms

Failure rate of colorectal cancer after surgical resection remains around 50% and adjuvant treatments are clearly required.. All patients with serosal involvement and/or lymph node metastases are at risk of recurrence (Dukes-Astler Coller B2, C1, C2). For thirty years many randomized trials testing chemotherapy and radiation therapy (rectum) have been conducted and some have demonstrated some kind of significant activity. We have analysed these trials and proposed with the EORTC GI tract cooperative group a new prospective randomized trial (40911).. In colon cancer, five trials have tested single agent systemic chemotherapy and failed to demonstrated a significant increase in survival. Four trials have tested systemic chemotherapy with 5-FU + MeCCNU +/- oncovin and only one (NSABP COI ant ROI) has demonstrated some significant benefit in term of survival. The combination of 5-FU + levamisole has been tested in 4 trials; in two there was a trend in favor of the treated group and in the intergroup trial there was a very significant increase in survival for Duke C patients. Six trials have tested the efficacy of post-operative local chemotherapy (intraportal); 3 demonstrated a significant increased survival and 2 a decrease in hepatic recurrence rate. Among the ongoing trials the EORTC 40911 aims to evaluate the interest of combining systemic chemotherapy (5-FU + levamisole or 5-FU + 1 folinic acid) to postoperative local chemotherapy (intraportal or intraperitoneal). In rectal cancer, preoperative radiation therapy significantly decreases the local recurrence rate, more than post-operative radiation therapy. The combination of post-operative radiation therapy with chemotherapy increases significantly survival rate. Presently patients with mobile rectal tumor located at the middle or the upper part of the rectum should be when possible randomized in trials such as the EORTC 40911. Concerning patients with large tumor located at the inferior part of the rectum new trials combining preoperative radiotherapy chemotherapy will be initiated.. Some randomized trials using polychemotherapy have resulted in increasing survival rate in adjuvant setting regarding patients with colorectal cancer. New trials have been initiated to further improve these encouraging results.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colorectal Neoplasms; Combined Modality Therapy; Female; Fluorouracil; Humans; Infusions, Intravenous; Infusions, Parenteral; Leucovorin; Levamisole; Male; Portal Vein; Rectal Neoplasms; Risk Factors

Topics: Antineoplastic Combined Chemotherapy Protocols; Aspartic Acid; Colonic Neoplasms; Fluorouracil; Humans; Leucovorin; Methotrexate; Phosphonoacetic Acid; Rectal Neoplasms

Topics: Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Colonic Neoplasms; Fluorouracil; Forecasting; Humans; Leucovorin; Rectal Neoplasms

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Clinical Trials as Topic; Colonic Neoplasms; Doxorubicin; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Methotrexate; Rectal Neoplasms; Semustine; Vincristine

Patients with locally advanced rectal cancer treated with total neoadjuvant therapy (TNT) may achieve organ preservation without a compromise to oncologic outcomes. However, reports on patient compliance with TNT and with treatment-related toxicities are limited.. The OPRA trial assessed organ preservation rates and oncologic outcomes in patients with clinical stage II/III rectal adenocarcinoma randomized to induction chemotherapy followed by chemoradiation (INCT-CRT) or chemoradiation followed by consolidation chemotherapy (CRT-CNCT). Systemic chemotherapy consisted of 8 cycles (16 weeks) of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) or 5 cycles (15 weeks) of capecitabine and oxaliplatin (CAPEOX). Patients received >4500 cGy of radiation with sensitizing capecitabine or fluorouracil. In this report, we compare compliance and treatment-related toxicity in patients receiving INCT-CRT versus CRT-CNCT. Additionally, we evaluate the association of compliance to chemotherapy, compliance to chemoradiation, and toxicity with organ preservation and disease-free survival (DFS).. Of the 324 patients randomized, fewer patients started chemoradiation in the INCT-CRT group compared with the CRT-CNCT group (93% vs 98%, P = .03), and fewer patients started systemic chemotherapy in the CRT-CNCT group compared with the INCT-CRT group (94% vs 99%, P = .04). Order of TNT did not affect the ability to complete all intended cycles of FOLFOX (86% INCT-CRT vs 83% CRT-CNCT, P = .60) or CAPEOX (74% INCT-CRT vs 77% CRT-CNCT, P = .80). A total of 97% of INCT and 98% of CRT-CNCT patients received >4500 cGy radiation (P = .93). Sixty-four patients (41%) treated with INCT-CRT and 57 CRT-CNCT patients (34%) experienced a grade 3+ adverse event (P = .30). Compliance and toxicity were not associated with organ preservation or DFS.. We identified only minor differences in treatment compliance between patients treated with INCT-CRT and CRT-CNCT. No difference in adverse events was observed between groups. Treatment compliance and toxicity did not correlate with organ preservation rates or DFS.

Topics: Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemoradiotherapy; Fluorouracil; Humans; Leucovorin; Neoadjuvant Therapy; Neoplasm Staging; Oxaliplatin; Patient Compliance; Rectal Neoplasms; Treatment Outcome

Fluorouracil, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab is the standard second-line chemotherapy for patients with metastatic colorectal cancer (mCRC) who are refractory or intolerant to fluoropyrimidines and oxaliplatin. However, the benefits of incorporating fluoropyrimidines into second-line chemotherapy for patients with mCRC who are refractory to fluoropyrimidines are unknown.. We retrospectively evaluated patients with mCRC who were administered irinotecan plus bevacizumab or FOLFIRI plus bevacizumab as second-line chemotherapy at a single institution from January 2010 to April 2020. We compared the efficacy and safety of irinotecan plus bevacizumab (IRI group) with those of FOLFIRI plus bevacizumab (FOLFIRI group).. Of the 255 enrolled patients, 107 (IRI/FOLFIRI group, 31/76 patients) were eligible for analysis. After a median follow-up of 13.1 months (range 1.2-48.4) and 14.3 months (range 0.9-46.5) for the IRI and FOLFIRI groups, respectively, the median progression-free survival was 6.4 months and 5.8 months [adjusted hazard ratio (aHR), 0.82; 95% confidence interval (CI) 0.50-1.34, p = 0.44] and the median overall survival was 16.6 months and 16.5 months (aHR, 1.01; 95% CI 0.59-1.69; p = 0.97) in the IRI and FOLFIRI groups, respectively. All-grade nausea, stomatitis, neutropenia, thrombocytopenia, Grade 3/4 neutropenia, and febrile neutropenia occurred more frequently in the FOLFIRI group than in the IRI group.. Our study suggests omitting fluorouracil from FOLFIRI plus bevacizumab as the second-line chemotherapy decreases adverse events without affecting the treatment efficacy in patients with mCRC who are refractory to fluoropyrimidines. Further randomized prospective studies are warranted to validate our result.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Humans; Irinotecan; Leucovorin; Neutropenia; Rectal Neoplasms; Retrospective Studies

In patients with RAS wild-type metastatic colorectal cancer, depth of response (DpR) has gained importance as a novel end-point in clinical trials. We investigated the overall DpR, as well as the prognostic and predictive impact of DpR to induction therapy (six cycles of 5-fluorouracil, leucovorin [FU/FA], oxaliplatin [FOLFOX] and panitumumab [Pmab]) on consecutive maintenance therapy (FU/FA plus Pmab or FU/FA alone) in patients treated within the PanaMa trial.. Central radiological assessment was performed according to RECIST 1.1. DpR was defined as percentage change in tumour diameter within defined time intervals (induction therapy, maintenance therapy, total course of therapy). For prognostic and predictive analyses, median DpR (

Topics: Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Humans; Induction Chemotherapy; Leucovorin; Panitumumab; Rectal Neoplasms

Napabucasin is an investigational, orally administered reactive oxygen species generator bioactivated by intracellular antioxidant NAD(P)H:quinone oxidoreductase 1 that has been evaluated in various solid tumors, including metastatic colorectal cancer (mCRC). Phosphorylated signal transducer and activator of transcription 3 (pSTAT3) is hypothesized to predict response in napabucasin-treated patients with mCRC.. In the multi-center, open-label, phase III CanStem303C (NCT02753127) study, adults with histologically confirmed mCRC that progressed on first-line fluoropyrimidine plus oxaliplatin ± bevacizumab were randomized to twice-daily napabucasin plus FOLFIRI (napabucasin) or FOLFIRI alone (control). The primary endpoint was overall survival (OS) in the general study population and in patients with pSTAT3-positive tumors (biomarker-positive).. In the general study population (napabucasin, n = 624; control, n = 629), median OS was 14.3 months for napabucasin and 13.8 months for control (hazard ratio [HR], 0.976, one-sided P = .74). Overall, 44% of patients were biomarker-positive (napabucasin, n = 275; control, n = 272). In the biomarker-positive population, median OS was 13.2 months for napabucasin and 12.1 months for control (HR, 0.969; one-sided P > .99). In the control arm, median OS was shorter for biomarker-positive versus biomarker negative patients (12.1 vs. 18.5 months; HR, 1.518; nominal 2-sided P = .0002). The most common treatment-emergent adverse events (TEAEs) were diarrhea (napabucasin, 84.6%; control, 53.9%), nausea (60.5%, 50.5%), vomiting (41.2%, 29.3%), and abdominal pain (41.0%, 25.2%). Grade ≥3 TEAEs occurred in 73.8% of napabucasin-treated and 66.7% of control-treated patients, most commonly diarrhea (21.2%, 7.0%), neutrophil count decreased (13.7%, 19.2%), and neutropenia (13.3%, 15.2%). Safety was similar in biomarker-positive patients.. In patients with previously treated mCRC, adding napabucasin to FOLFIRI did not improve OS. Results from the control arm indicate that pSTAT3 is an adverse prognostic factor in mCRC.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Rectal Neoplasms

Differential tumor response to therapy is partially attributed to tumor heterogeneity. Additional efforts are needed to identify tumor heterogeneity parameters in response to therapy that is easily applicable in clinical practice. We aimed to describe tumor response-speed heterogeneity and evaluate its prognostic value in patients with metastatic colorectal cancer.. Individual patient data from Amgen (NCT00364013) and Sanofi (NCT00305188; NCT00272051) trials were retrieved from Project Data Sphere. Patients in the Amgen 5-fluorouracil, leucovorin, oxaliplatin (FOLFOX) arm were used to establish response-speed heterogeneity. Its prognostic value was subsequently validated in the Sanofi FOLFOX arms and the Amgen panitumumab+FOLFOX arm. Kaplan-Meier method and Cox proportional hazards models were used for survival analyses.. Patients with high response-speed heterogeneity in the Amgen FOLFOX cohort had significantly shorter ( P <0.001) median progression-free survival (PFS) of 7.27 months (95% CI, 6.12-7.96 mo) and overall survival (OS) of 16.0 months (95% CI, 13.8-18.2 mo) than patients with low response-speed heterogeneity with median PFS of 9.41 months (95% CI, 8.75-10.89 mo) and OS of 22.4 months (95% CI, 20.1-26.7 mo), respectively. Tumor response-speed heterogeneity was a poor prognostic factor of shorter PFS (hazard ratio, 4.17; 95% CI, 2.49-6.99; P <0.001) and shorter OS (hazard ratio, 2.57; 95% CI, 1.64-4.01; P <0.001), after adjustment for other common prognostic factors. Comparable findings were found in the external validation cohorts.. Tumor response-speed heterogeneity to first-line chemotherapy was a novel prognostic factor associated with early disease progression and shorter survival in patients with metastatic colorectal cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Oxaliplatin; Prognosis; Rectal Neoplasms; Treatment Outcome

Analysis of methylation markers in liquid biopsies is a promising technique for the follow-up of patients with metastatic colorectal cancer (mCRC), because they can be used in all patients, regardless of their mutational status. Therefore, we studied the value of NPY methylation analysis in circulating tumor DNA (ctDNA) for accurate response monitoring in patients with mCRC in the PANIB trial.. The PANIB trial was a randomized phase II trial designed to compare FOLFOX plus panitumumab and FOLFOX plus bevacizumab in patients with RAS wild-type unresectable mCRC. The results of sequential liquid biopsies were correlated with results of imaging.. Forty patients were included from six Belgian hospitals. Analysis of the liquid biopsies revealed that higher baseline levels of methylated ctDNA was associated with a significantly shorter overall survival [HR, 1.015; 95% confidence interval (CI), 1.005-1.025; P = 0.002]. Furthermore, 37 patients provided at least two liquid biopsies. Thirty-one of them showed a decrease in the methylation ratio after the start of therapy, which corresponded with stable disease or response on imaging at the first evaluation. When comparing the panitumumab and bevacizumab arm, significantly higher objective response and early tumor shrinkage rates were observed in the panitumumab arm (P = 0.048 and 0.015, respectively). However, due to a small study population, the trial was underpowered to detect a significant difference in survival.. The results of this study confirm that baseline methylated ctDNA is a prognostic marker and indicate that NPY methylation is a promising marker for response monitoring in patients with mCRC.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Biomarkers; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Panitumumab; Rectal Neoplasms

Trop-2 and Nectin-4 are transmembrane proteins overexpressed in many tumours and targets of antibody-drug conjugates (ADC). In metastatic colorectal cancer (mCRC), the role of Trop-2 and Nectin-4 has been poorly investigated.. Tumour samples of patients randomised in the phase III TRIBE2 were assessed for Trop-2 and Nectin-4 expression.. Three hundred eighty-six tumours were assessed for Trop-2 expression. 90 (23%), 115 (30%) and 181 (47%) were Trop-2 high, medium and low, respectively. Patients with low Trop-2 tumours achieved longer PFS (12 versus 9.9 months, p = 0.047) and OS (27.3 versus 21.3 months, p = 0.015) than those with high/medium Trop-2 tumours. These findings were confirmed in multivariate analysis (p = 0.022 and p = 0.023, respectively). A greater OS benefit from treatment intensification with FOLFOXIRI/bevacizumab was observed in patients with high/medium Trop-2 tumours (p-for-interaction = 0.041). Two hundred fifty-one tumours were assessed for Nectin-4 expression. Fourteen (5%), 67 (27%) and 170 (68%) were high, medium and low, respectively. No prognostic impact was observed based on Nectin-4 expression and no interaction effect was reported between Nectin-4 expression groups and treatment arm.. In mCRC, expression levels of Trop-2 and Nectin-4 are heterogeneous, suggesting a target-driven development of anti-Trop2 and anti-Nectin-4 ADCs. Medium/high Trop-2 expression is associated with worse prognosis and higher benefit from chemotherapy intensification.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Prognosis; Rectal Neoplasms

AtezoTRIBE phase II randomized study demonstrated that adding atezolizumab to first-line FOLFOXIRI (5-fluorouracil, oxaliplatin, irinotecan) plus bevacizumab prolongs progression-free survival (PFS) of patients with metastatic colorectal cancer (mCRC), with a modest benefit among proficient mismatch repair (pMMR). DetermaIO is an immune-related 27-gene expression signature able to predict benefit from immune checkpoint inhibition in triple-negative breast cancer. In this analysis of AtezoTRIBE, we investigated the predictive impact of DetermaIO in mCRC.. Patients with mCRC unselected for MMR status were randomly assigned (1:2) to FOLFOXIRI plus bevacizumab (control arm) or the same regimen with atezolizumab (atezolizumab arm). qRT-PCR by DetermaIO was performed on RNA purified from pretreatment tumors of 132 (61%) of 218 enrolled patients. A binary result (IOpos vs. IOneg) adopting the preestablished DetermaIO cut-off point (0.09) was obtained, and an exploratory optimized cut-off point (IOOPT) was computed in the overall population and in pMMR subgroup (IOOPTpos vs. IOOPTneg).. DetermaIO was successfully determined in 122 (92%) cases, and 23 (27%) tumors were IOpos. IOpos tumors achieved higher PFS benefit from atezolizumab arm than IOneg (HR: 0.39 vs. 0.83; Pinteraction = 0.066). In pMMR tumors (N = 110), a similar trend was observed (HR: 0.47 vs. 0.93; Pinteraction = 0.139). In the overall population, with the computed IOOPT cut-off point (0.277), 16 (13%) tumors were IOOPTpos and they derived higher PFS benefit from atezolizumab than IOOPTneg (HR: 0.10 vs. 0.85, Pinteraction = 0.004). Similar results were found in the pMMR subgroup.. DetermaIO may be useful to predict benefit of adding atezolizumab to first-line FOLFOXIRI plus bevacizumab in mCRC. The exploratory IOOPT cut-off point should be validated in independent mCRC cohorts.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Rectal Neoplasms; Transcriptome

Total neoadjuvant therapy (TNT) is a novel treatment strategy that is an alternative to preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC). However, an optimal protocol for TNT has not yet been established. The present study will be an open-label, single-arm, single-center trial to develop a new protocol.. Thirty LARC patients at high risk of distant metastasis will receive CRT consisting of long-course radiation, concurrent with tegafur/uracil, oral leucovorin, irinotecan (TEGAFIRI), followed by mFOLFOX-6 or CAPOX before undergoing surgery.. Since previous findings showed a high percentage of grade 3-4 adverse events with the TEGAFIRI regimen for CRT and TNT, the primary outcome of this study will be safety and feasibility. Our regimen for CRT consists of the biweekly administration of irinotecan for good patient compliance. The novel combination approach of this treatment may improve the long-term outcomes of LARC.. Japan Registry of Clinical Trials jRCTs031210660.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Clinical Trials, Phase II as Topic; Fluorouracil; Humans; Irinotecan; Leucovorin; Neoadjuvant Therapy; Neoplasm Staging; Oxaliplatin; Rectal Neoplasms; Tegafur; Treatment Outcome

The standard of care for locally advanced rectal cancer in North America is neoadjuvant pelvic chemoradiation with fluorouracil (5FUCRT). Neoadjuvant chemotherapy with fluorouracil and oxaliplatin (FOLFOX) is an alternative that may spare patients the morbidity of radiation. Understanding the relative patient experiences with these options is necessary to inform treatment decisions.. PROSPECT was a multicenter, unblinded, noninferiority, randomized trial of neoadjuvant FOLFOX versus 5FUCRT, which enrolled adults with rectal cancer clinically staged as T2N+, cT3N-, or cT3N+ who were candidates for sphincter-sparing surgery. Neoadjuvant FOLFOX was given in six cycles over 12 weeks, followed by surgery. Neoadjuvant 5FUCRT was delivered in 28 fractions over 5.5 weeks, followed by surgery. Adjuvant chemotherapy was suggested but not mandated in both groups. Enrolled patients were asked to provide patient-reported outcomes (PROs) at baseline, during neoadjuvant treatment, and at 12 months after surgery. PROs included 14 symptoms from the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Additional PRO instruments measured bowel, bladder, sexual function, and health-related quality of life (HRQL).. From June 2012 to December 2018, 1,194 patients were randomly assigned, 1,128 initiated treatment, and 940 contributed PRO-CTCAE data (493 FOLFOX; 447 5FUCRT). During neoadjuvant treatment, patients reported significantly lower rates of diarrhea and better overall bowel function with FOLFOX while anxiety, appetite loss, constipation, depression, dysphagia, dyspnea, edema, fatigue, mucositis, nausea, neuropathy, and vomiting were lower with 5FUCRT (all multiplicity adjusted. For patients with locally advanced rectal cancer choosing between neoadjuvant FOLFOX and 5FUCRT, the distinctive PRO profiles inform treatment selection and shared decision making.

Topics: Adult; Anal Canal; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Leucovorin; Neoadjuvant Therapy; Neoplasm Staging; Organ Sparing Treatments; Patient Reported Outcome Measures; Quality of Life; Rectal Neoplasms; Treatment Outcome

Pelvic radiation plus sensitizing chemotherapy with a fluoropyrimidine (chemoradiotherapy) before surgery is standard care for locally advanced rectal cancer in North America. Whether neoadjuvant chemotherapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) can be used in lieu of chemoradiotherapy is uncertain.. We conducted a multicenter, unblinded, noninferiority, randomized trial of neoadjuvant FOLFOX (with chemoradiotherapy given only if the primary tumor decreased in size by <20% or if FOLFOX was discontinued because of side effects) as compared with chemoradiotherapy. Adults with rectal cancer that had been clinically staged as T2 node-positive, T3 node-negative, or T3 node-positive who were candidates for sphincter-sparing surgery were eligible to participate. The primary end point was disease-free survival. Noninferiority would be claimed if the upper limit of the two-sided 90.2% confidence interval of the hazard ratio for disease recurrence or death did not exceed 1.29. Secondary end points included overall survival, local recurrence (in a time-to-event analysis), complete pathological resection, complete response, and toxic effects.. From June 2012 through December 2018, a total of 1194 patients underwent randomization and 1128 started treatment; among those who started treatment, 585 were in the FOLFOX group and 543 in the chemoradiotherapy group. At a median follow-up of 58 months, FOLFOX was noninferior to chemoradiotherapy for disease-free survival (hazard ratio for disease recurrence or death, 0.92; 90.2% confidence interval [CI], 0.74 to 1.14; P = 0.005 for noninferiority). Five-year disease-free survival was 80.8% (95% CI, 77.9 to 83.7) in the FOLFOX group and 78.6% (95% CI, 75.4 to 81.8) in the chemoradiotherapy group. The groups were similar with respect to overall survival (hazard ratio for death, 1.04; 95% CI, 0.74 to 1.44) and local recurrence (hazard ratio, 1.18; 95% CI, 0.44 to 3.16). In the FOLFOX group, 53 patients (9.1%) received preoperative chemoradiotherapy and 8 (1.4%) received postoperative chemoradiotherapy.. In patients with locally advanced rectal cancer who were eligible for sphincter-sparing surgery, preoperative FOLFOX was noninferior to preoperative chemoradiotherapy with respect to disease-free survival. (Funded by the National Cancer Institute; PROSPECT ClinicalTrials.gov number, NCT01515787.).

Topics: Adult; Anal Canal; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Chemotherapy, Adjuvant; Disease-Free Survival; Fluorouracil; Humans; Leucovorin; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Organ Sparing Treatments; Oxaliplatin; Preoperative Care; Preoperative Period; Rectal Neoplasms

In clinical trials, the assessment of safety is traditionally focused on the overall rate of high-grade and serious adverse events (AEs). A new approach to AEs evaluation, taking into account chronic low-grade AEs, single patient's perspective, and time-related information, such as ToxT analysis, should be considered especially for less intense but potentially long-lasting treatments, such as maintenance strategies in metastatic colorectal cancer (mCRC).. We applied ToxT (Toxicity over Time) evaluation to a large cohort of mCRC patients enroled in randomised TRIBE, TRIBE2, and VALENTINO studies, in order to longitudinally describe AEs throughout the whole treatment duration and to compare AEs evolution over cycles between induction and maintenance strategies, providing numerical and graphical results overall and per single patient. After 4-6 months of combination therapy, 5-fluorouracil/leucovorin (5-FU/LV) + bevacizumab or panitumumab was recommended in all studies except for the 50% of patients in the VALENTINO trial who received panitumumab alone.. Out of 1400 patients included, 42% received FOLFOXIRI (5-FU/LV, oxaliplatin, and irinotecan)/bevacizumab, 18% FOLFIRI/bevacizumab, 24% FOLFOX/bevacizumab, 16% FOLFOX/panitumumab. Mean grade of general and haematological AEs was higher in the first cycles, then progressively decreasing after the end of induction (p < 0.001), and always remaining at the highest levels with FOLFOXIRI/bevacizumab (p < 0.001). Neurotoxicity became more frequent over the cycles with late high-grade episodes (p < 0.001), while the incidence but not the grade of hand-and-foot syndrome gradually increased (p = 0.91). Anti-VEGF-related AEs were more severe in the first cycles, then setting over at low levels (p = 0.03), while anti-EGFR-related AEs still affected patients during maintenance.. Most of chemotherapy-related AEs (except for HFS and neuropathy) reach the highest level in the first cycles, then decrease, probably due to their active clinical management. Transition to maintenance allows relief from most AEs, especially with bevacizumab-based regimens, while anti-EGFR-related AEs may persist.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Panitumumab; Rectal Neoplasms

In this controlled, randomized, open-label phase II trial, 109 patients were randomly assigned, 107 of whom were included into the full analysis set (FAS). Patients were randomly assigned in a 2:1 ratio to receive either FOLFOXIRI plus cetuximab in the experimental arm (n = 72) or FOLFOXIRI plus bevacizumab in the control arm (n = 35). The primary end point was objective response rate (ORR) according to RECIST 1.1., evaluated in patients treated according to protocol (ATP population). Progression-free survival (PFS), overall survival (OS), toxicity, and feasibility were analyzed as secondary end points.. Eighteen patients discontinued study treatment before the first tumor assessment, thus resulting in the ATP population of 89 patients. In these patients, ORR was 51% (30/59) in the cetuximab-based experimental arm and 67% (20/30) in the bevacizumab-based control arm (odds ratio, 1.93; 80% CI, 1.06 to 3.52;. To our knowledge, FIRE-4.5 is the first prospective and randomized study investigating first-line treatment of

Topics: Adenosine Triphosphate; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Cetuximab; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Prospective Studies; Proto-Oncogene Proteins B-raf; Rectal Neoplasms

Anti-EGFR antibodies plus doublet chemotherapy is the standard of care in RAS/BRAF wild-type metastatic colorectal cancer (mCRC). No phase-3 level of evidence is available to guide treatment de-escalation after anti-EGFR-based first-line. Several randomised clinical trials investigated de-intensification strategies with 5-fluorouracil/leucovorin (5-FU/LV) and/or anti-EGFR.. We performed an individual patient data pooled analysis of Valentino, Panama, MACRO-2, COIN-B trials including RAS wild-type mCRC patients who received first-line therapy with FOLFOX plus panitumumab or cetuximab followed by pre-specified maintenance strategy. Only patients who started maintenance according to the assigned arm were included. Patients were categorised by type of maintenance (i.e. 5-FU/LV, anti-EGFR or 5-FU/LV + anti-EGFR). Progression-free survival (PFS) and overall survival (OS) were calculated from the start of maintenance; toxicity was evaluated for the maintenance treatment period.. A total of 518 patients were included in the pooled analysis. Overall, 123, 185 and 210 patients received maintenance with 5-FU/LV, anti-EGFR, 5-FU/LV + anti-EGFR, respectively. Median PFS was 5.6, 6.0 and 9.0 (P = 0.009) and OS was 25.7, 24.0 and 28.0 months (P = 0.134) in 5-FU/LV, anti-EGFR and 5-FU/LV + anti-EGFR arms, respectively. Monotherapy maintenance (either 5-FU/LV or anti-EGFR) was inferior to combination in terms of PFS (hazard ratios [HR] 1.26, P = 0.016) and non-significantly trending also in OS (HR 1.20, P = 0.111). An increase of overall any grade and grade ≥ 3 AEs and selected AEs was reported in combination compared to either 5-FU/LV or anti-EGFR arms.. This pooled analysis including four randomised phase II supports the use of 5-FU/LV plus anti-EGFR as the preferred maintenance regimen. Data provide rational for a more individualised maintenance treatment approach based on tumour and patients features.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cetuximab; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Humans; Induction Chemotherapy; Leucovorin; Rectal Neoplasms

The PanaMa trial demonstrated significant benefit in progression-free survival with the addition of panitumumab (Pmab) to fluorouracil and folinic acid (FU/FA) as maintenance therapy following first-line induction therapy with FOLFOX/Pmab in patients with RAS wild-type metastatic colorectal cancer. Here, we report health-related quality of life (HRQOL) analyses from the PanaMa trial.. HRQOL outcomes were evaluated using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) at every cycle of therapy until disease progression/death. HRQOL outcomes were mean and individual changes in EORTC QLQ-C30 from baselines (before induction therapy and before maintenance therapy) to each cycle of treatment. Comparative analyses were performed by randomisation status and treatment arm for induction- and maintenance-therapy, respectively. The trial is registered with clinicaltrials.gov (NCT01991873).. At least one HRQOL questionnaire was completed by a total of 349/377 (93%) patients who received induction therapy, and by 237/248 (96%) patients who were randomised and received maintenance therapy. During induction therapy, most HRQOL dimensions remained stable or showed improvement, while appetite loss and diarrhoea significantly deteriorated. During maintenance therapy, HRQOL dimensions remained stable, while those that deteriorated during induction therapy showed significant improvement, without significant differences between the treatment arms.. Maintenance therapy improves HRQOL dimensions that initially deteriorated during induction therapy while stabilising HRQOL in other dimensions. The addition of Pmab to FU/FA as maintenance therapy in patients with RAS wild-type metastatic colorectal cancer prolongs progression-free survival without negative impact on HRQOL.

Topics: Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Panitumumab; Quality of Life; Rectal Neoplasms

Triplet chemotherapy might be more effective than doublet chemotherapy in metastatic colorectal cancer (mCRC), but it may also be marked by increased toxicity. To investigate whether. Seventy patients with mCRC were randomly assigned (1:1) to receive FOLFOXIRI plus either. The addition of

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Middle Aged; Oxaliplatin; Rectal Neoplasms; Tocotrienols; Young Adult

The optimal maintenance strategy after induction chemotherapy with anti-epidermal growth factor receptor antibody for patients with RAS wild-type metastatic colorectal cancer (mCRC) remains to be debated.. To evaluate the efficacy and safety of maintenance therapy with single-agent cetuximab after FOLFIRI (leucovorin [folinic acid], fluorouracil, and irinotecan) plus cetuximab induction therapy.. The TIME (Treatment After Irinotecan-Based Frontline Therapy: Maintenance With Erbitux]) (PRODIGE 28 [Partenariat de Recherche en Oncologie Digestive]-UCGI 27 [UniCancer GastroIntestinal Group]) phase 2 noncomparative, multicenter randomized clinical trial was conducted from January 15, 2014, to November 23, 2018, among 139 patients with unresectable RAS wild-type mCRC. The cutoff date for analysis was July 21, 2022.. After first-line induction therapy with 8 cycles of FOLFIRI plus cetuximab, patients without disease progression were randomized (1:1) to biweekly maintenance with cetuximab or observation. On disease progression, the same induction regimen was recommended for 16 weeks followed by further maintenance with cetuximab or observation until disease progression under the full induction regimen.. The primary end point was the 6-month progression-free rate from randomization. Analysis was performed on an intention-to-treat basis. An exploratory biomolecular analysis, using next-generation sequencing, investigated the putative prognostic value of the tumor mutation profile.. Of 214 patients enrolled (141 men [65.9%]; median age, 67 years [range, 23-85 years]), 139 were randomized to receive cetuximab (n = 67; 45 men [67.2%]; median age, 64 years [range, 34-85 years]) or to be observed (n = 72; 50 men [69.4%]; median age, 68 years [23-85 years]). The 6-month progression-free rate was 38.8% ([26 of 67] 95% CI, 27.1%-51.5%) in the cetuximab group and 5.6% ([4 of 72] 95% CI, 1.5%-13.6%) in the observation group. At a median follow-up of 40.5 months (95% CI, 33.6-47.5 months), median progression-free survival (PFS) from randomization was 5.3 months (95% CI, 3.7-7.4 months) in the cetuximab group and 2.0 months (95% CI, 1.8-2.7 months) in the observation group. Median overall survival (OS) was 24.8 months (95% CI, 18.7-30.4 months) in the cetuximab group and 19.7 months (95% CI, 13.3-24.4 months) in the observation group. In an exploratory multivariate analysis, any tumor-activating mutation in the mitogen-activated protein kinase (MAPK) pathway genes was associated with shorter PFS from randomization regardless of treatment group (hazard ratio, 1.63 [95% CI, 1.01-2.62]; P = .04). The most frequent grade 3 or 4 treatment-related toxic effect in the cetuximab group during maintenance therapy was rash (8 of 67 [11.9%]).. The randomized clinical trial did not meet its primary end point but suggests clinically meaningful PFS and OS benefits associated with cetuximab maintenance therapy. However, maintenance cetuximab or treatment breaks after first-line combination FOLFIRI-cetuximab therapy seems inappropriate for patients with MAPK-mutated independently of the side of primary tumor. A more complete assessment of MAPK pathway mutations warrants further investigation to the refine treatment strategy for patients with RAS wild-type mCRC.. ClinicalTrials.gov Identifier: NCT02404935.

Topics: Aged; Cetuximab; Colonic Neoplasms; Disease Progression; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Rectal Neoplasms

Organ preservation is now considered an acceptable alternative option in distal rectal cancer patients with clinical complete response (cCR) after neoadjuvant chemoradiation (CRT). But the cCR rate is low and about one-third of tumour will regrow, which requires more effective local treatment. CRT combined with intra-arterial chemotherapy (IAC) might be a promising approach. Additionally, total neoadjuvant therapy using FOLFIRINOX induction chemotherapy improved survival while consolidation chemotherapy improved organ preservation. We assess whether IAC plus CRT and FOLFIRINOX consolidation chemotherapy can improve the chance of organ preservation and survival in distal rectal cancer.. This prospective, monocentric, open-label, single-arm phase II study will include 32 patients with cT3-4NanyM0 distal rectal adenocarcinoma. All patients will receive one cycle of IAC (irinotecan, raltitrexed and oxaliplatin), followed by CRT (50 Gy/25 fractions with concomitant capecitabine) and then with six cycles of FOLFIRINOX (leucovorin, 5-fluorouracil, oxaliplatin and irinotecan). After final evaluation, patients with cCR will receive non-operative management or surgery at their own discretion and others are mandatorily referred to surgery. Adjuvant chemotherapy with six cycles of mFOLFOX6 (leucovorin, 5-fluorouracil and oxaliplatin) will be used for patients with adverse pathological features. The primary endpoint is the rate of complete response (CR; pathological CR or sustained cCR≥2 years). The main secondary endpoints are toxicity, compliance, short-term and long-term oncological outcomes, surgical morbidity and quality of life. This protocol has been designed in accordance with the Standard Protocol Items: Recommendations for Interventional Trials 2013 guidelines.. This study was approved by the Academic and Ethics Committee of The Affiliated Hospital of Youjiang Medical University for Nationalities in March 2023. Trial results will be published in peer-reviewed international journals and on the ChiCTR website.. Registered on 18 April 2023; version #1.. ChiCTR2300070620.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Clinical Trials, Phase II as Topic; Fluorouracil; Humans; Irinotecan; Leucovorin; Neoadjuvant Therapy; Neoplasm Staging; Oxaliplatin; Pancreatic Neoplasms; Prospective Studies; Quality of Life; Rectal Neoplasms

Many clinical trials for older patients with metastatic colorectal cancer have been conducted, and fluoropyrimidine and bevacizumab are standard treatments. However, the relationship between age and the efficacy and safety of this treatment is unclear in older metastatic colorectal cancer patients.. Individual data from two phase II studies on older (≥75 years), non-frail patients with metastatic colorectal cancer treated with uracil-tegafur/leucovorin or S-1 combined with bevacizumab were collected. Patient characteristics were evaluated with multiple regression analyses for survival outcomes, using the Cox proportional hazard model and linear regression analyses for the worst grade of adverse events.. We enrolled 102 patients with a median age of 80 years (range, 75-88 years). Of the 70 patients who died, seven (10%) died of causes unrelated to disease or treatment. The study treatment was discontinued due to adverse events in 19 patients (18.6%), with 63% aged ≥85 years. The adverse event that most commonly resulted in treatment discontinuation was grade 2 fatigue (21%). Chronological age was not associated with progression-free survival (Hazard ratio, 1.03; P = 0.40) or overall survival (Hazard ratio, 1.02; P = 0.65). Age was weakly associated with non-hematologic adverse events (regression coefficient [R], 0.27; P = 0.007), especially fatigue (R, 0.23; P = 0.02) and nausea (R, 0.19; P = 0.06), but not with hematologic (R, 0.05; P = 0.43) or bevacizumab-related (R, -0.06; P = 0.56) adverse events.. The efficacy of fluoropyrimidine plus bevacizumab was age-independent in patients with metastatic colorectal cancer aged ≥75 years, and attention should be paid to non-hematologic adverse events as age increases.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colonic Neoplasms; Colorectal Neoplasms; Disease-Free Survival; Fatigue; Fluorouracil; Humans; Leucovorin; Rectal Neoplasms

The evidence on the efficacy of anticancer therapy is limited in older patients with metastatic colorectal cancer (mCRC). This retrospective analysis of phase III FIRE-3 trial assesses the efficacy of FOLFIRI plus either cetuximab or bevacizumab according to the patients' age and sidedness of primary tumour.. The study endpoints overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) were compared between younger (<65 years) and older (≥65 years) patients, followed by stratification according to primary tumour sidedness. ORR was compared using Fisher´s exact test, OS and PFS were estimated by the Kaplan-Meier method and compared using the log-rank test. Univariate Cox regression analyses assessed hazard ratios and 95% confidence intervals for OS and PFS.. Overall, older patients with RAS WT tumours had a significantly shorter OS when compared to younger patients (25.9 months vs 29.3 months, HR 1.29; P = 0.02). Also the proportion of right-sided tumours was significantly greater in older patients (27.1% vs 17.9%; P = 0.029). Secondary resection rates were numerically higher in younger patients (25.4% vs. 17.6%, P = 0.068) than in older patients. This was primarily seen in the Cetuximab arm, where older patients underwent less likely resection (13.1% vs. 26%; P = 0.02). Older patients with left-sided tumours showed only a trend towards greater efficacy of cetuximab (HR 0.86; P = 0.38). In patients with right-sided primary tumours, older patients did not appear to benefit from cetuximab in contrast to younger patients (≥65 years: 16.6 months vs 23.6 months, HR 1.1; P = 0.87; <65 years: 21.9 months vs 16.4 months HR 1.5; P = 0.31).. In FIRE-3, OS was generally shorter in older patients in comparison to younger patients. This could be explained by the overrepresentation of right-sided tumours and a lower secondary resection rate in older patients. The efficacy of targeted therapy was dependent on tumour sidedness in older patients with RAS WT mCRC.. FIRE-3 (NCT00433927).

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Cetuximab; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Rectal Neoplasms; Retrospective Studies

Reactive oxygen species activate EGFR/RAS/MAPK signaling either through the inactivation of phosphatases or by direct oxidation of kinases. We hypothesized that functional single-nucleotide polymorphisms (SNPs) in antioxidant genes link to the efficacy of cetuximab in patients with metastatic colorectal cancer (mCRC).. We analyzed genomic and clinical data from FIRE-3, a phase III trial comparing cetuximab and bevacizumab along with FOLFIRI in untreated mCRC patients. Genomic DNA extracted from blood samples was genotyped. Thirteen functional SNPs in antioxidant genes were tested for associations with clinical outcomes.. In total, 236 patients were included (FOLFIRI/cetuximab arm, n = 129; FOLFIRI/bevacizumab arm, n = 107). In univariate analysis, two SNPs (TXN2 rs4821494 and GPX4 rs4807542) were significantly associated with overall survival (OS) in the FOLFIRI/cetuximab arm. Multivariate analysis confirmed the significant association of TXN2 rs4821494 (T/T vs. any G allele, hazard ratio = 2.47, 95% confidence interval = 1.06-5.72, P = .03). In the FOLFIRI/bevacizumab arm, no SNPs were significantly associated with clinical outcomes. Treatment-by-SNP interaction test confirmed the predictive value of TXN2 rs4821494 (OS: P = .03).. TXN2 rs4821494 involved in the antioxidant system may predict the efficacy of cetuximab-based first-line chemotherapy in mCRC, warranting further validation studies.

Topics: Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Bevacizumab; Camptothecin; Cetuximab; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Germ Cells; Humans; Leucovorin; Rectal Neoplasms

This multicenter single-arm, phase II study evaluated the efficacy and safety of uninterrupted panitumumab usage combined with cytotoxic doublets for unresectable/metastatic colorectal cancer (mCRC). Additionally, clinical value of the RAS/BRAF mutation status in circulating cell-free DNA (ccfDNA) was evaluated; this evaluation was measured independently of the protocol treatment. Eligible patients with RAS wild-type mCRC who had received the first-line panitumumab plus FOLFOX treatment were recruited and administered continuous panitumumab combined with FOLFIRI. Progression-free survival (PFS) at 6 months was the primary endpoint, with threshold and expected values of 35% and 50%, respectively. In total, 54 patients were enrolled between October 2017 and October 2019. The crude 6-month PFS rate was 37.0%, with a 4.8-month median PFS. The response rate and disease control rate were 16.7% and 50.0%, respectively. Notably, of the 54 participants, 17 showed RAS/BRAF mutations until the end of the protocol treatment and of the 22 patients with progressive disease as their best response, 10 possessed RAS/BRAF mutations in their plasma ccfDNA at baseline. The median PFS significantly differed among patients harboring tumors with BRAF and RAS mutations and those with wild-type tumors. In conclusion, our study failed to show the expected efficacy of the continuous panitumumab use in the second-line treatment. Liquid biopsy discriminated the duration of PFS according to the mutation status. The effectiveness of continuous treatment with panitumumab should be evaluated in patients with RAS/BRAF wild-type mCRC determined by liquid biopsy at the start of the second-line treatment.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cell-Free Nucleic Acids; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Mutation; Panitumumab; Proto-Oncogene Proteins B-raf; Rectal Neoplasms

Cetuximab in combination with chemotherapy is a standard first-line treatment regimen for patients with metastatic colorectal cancer (mCRC) RAS wild-type (wt); however, the efficacy of cetuximab plus leucovorin, fluorouracil and oxaliplatin (FOLFOX) had never been demonstrated in a prospective, randomized, controlled phase III study. The TAILOR study is the first randomized, multicenter, prospective Phase III study evaluating the addition of cetuximab to FOLFOX in a RAS wt Chinese population and thus providing confirmatory data for the efficacy and safety of cetuximab plus FOLFOX versus FOLFOX alone.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cetuximab; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Neoplasm Metastasis; Organoplatinum Compounds; Prospective Studies; Rectal Neoplasms

Panitumumab plus FOLFOX (P-FOLFOX) is standard first-line treatment for RAS wild-type (WT) metastatic colorectal cancer. The value of panitumumab rechallenge is currently unknown. We assessed addition of panitumumab to FOLFIRI (P-FOLFIRI) beyond progression to P-FOLFOX in patients with no RAS mutations in liquid biopsy (LB).. In this randomized phase II trial, patients were assigned (3:2 ratio) to second-line P-FOLFIRI (arm A) or FOLFIRI alone (arm B). LB for circulating tumor DNA analysis was collected at study entry and at disease progression. Primary endpoint was 6-month progression-free survival. Two-stage Simon design required 85 patients to be included (EudraCT 2017-004519-38).. Between February 2019 and November 2020, 49 patients were screened (16 RAS mutations in LB detected) and 31 included (18 assigned to arm A and 13 to arm B). The study was prematurely closed due to inadequate recruitment. Serious adverse events were more frequent in arm A (44% vs. 23%). Overall response rate was 33% (arm A) vs. 7.7% (arm B). Six-month progression-free survival rate was 66.7% (arm A) and 38.5% (arm B). Median progression-free survival was 11.0 months (arm A) and 4.0 months (arm B) (hazard ratio, 0.58). At disease progression, RAS or BRAF mutations in LB were found in 4/11 patients (36%) in arm A and 2/10 (20%) in arm B.. The BEYOND study suggests a meaningful benefit of P-FOLFIRI beyond progression to P-FOLFOX in metastatic colorectal cancer patients with WT RAS status selected by LB. This strategy deserves further investigation.

Topics: Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Circulating Tumor DNA; Colonic Neoplasms; Colorectal Neoplasms; Disease Progression; Fluorouracil; Humans; Leucovorin; Panitumumab; Proto-Oncogene Proteins B-raf; Rectal Neoplasms

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colonic Neoplasms; Colorectal Neoplasms; Disease-Free Survival; Fluorouracil; Humans; Leucovorin; Rectal Neoplasms

To compare the efficacy and safety of high-dose vitamin C plus FOLFOX ± bevacizumab versus FOLFOX ± bevacizumab as first-line treatment in patients with metastatic colorectal cancer (mCRC).. Between 2017 and 2019, histologically confirmed patients with mCRC (n = 442) with normal glucose-6-phosphate dehydrogenase status and no prior treatment for metastatic disease were randomized (1:1) into a control (FOLFOX ± bevacizumab) and an experimental [high-dose vitamin C (1.5 g/kg/d, intravenously for 3 hours from D1 to D3) plus FOLFOX ± bevacizumab] group. Randomization was based on the primary tumor location and bevacizumab prescription.. The progression-free survival (PFS) of the experimental group was not superior to the control group [median PFS, 8.6 vs. 8.3 months; HR, 0.86; 95% confidence interval (CI), 0.70-1.05; P = 0.1]. The objective response rate (ORR) and overall survival (OS) of the experimental and control groups were similar (ORR, 44.3% vs. 42.1%; P = 0.9; median OS, 20.7 vs. 19.7 months; P = 0.7). Grade 3 or higher treatment-related adverse events occurred in 33.5% and 30.3% of patients in the experimental and control groups, respectively. In prespecified subgroup analyses, patients with RAS mutation had significantly longer PFS (median PFS, 9.2 vs. 7.8 months; HR, 0.67; 95% CI, 0.50-0.91; P = 0.01) with vitamin C added to chemotherapy than with chemotherapy only.. High-dose vitamin C plus chemotherapy failed to show superior PFS compared with chemotherapy in patients with mCRC as first-line treatment but may be beneficial in patients with mCRC harboring RAS mutation.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Bevacizumab; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Glucosephosphate Dehydrogenase; Humans; Leucovorin; Rectal Neoplasms

The randomised open-label phase III XELAVIRI trial failed to demonstrate non-inferiority of the sequential application of fluoropyrimidine plus bevacizumab followed by additional irinotecan at first progression (Arm A) versus initial combination of all agents (Arm B) for untreated metastatic colorectal cancer in the initial analysis of time-to-failure-of-strategy (TFS, 90% confidence boundary of 0.8). Here, we evaluate efficacy in the full analysis set (FAS), the per-protocol set, in addition to age-related and molecular subgroups.. Median TFS, overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier method and log-rank test. Cox regression models assessed hazard ratios (HRs) and confidence intervals (CIs) (TFS: 90%; OS, PFS: 95%).. Of 421 patients, 390 (92.6%), 391 (92.9%) and 357 (84.8%) events for TFS, OS and PFS were observed in the FAS with a median follow-up of 54.2 months (Arm A) versus 52.9 months (Arm B). Non-inferiority of sequential treatment for TFS was missed in the FAS (HR 0.93; 90% CI, 0.79-1.10; P = 0.482) and not shown in the per-protocol set (HR 0.93; 90% CI, 0.75-1.13, P = 0.433). Formal non-inferiority for TFS was observed for patients older than 70 years (HR 1.06; 90% CI, 0.80-1.41; P = 0.670) and patients with RAS mutant tumours (HR 1.12; 90% CI, 0.87-1.43; P = 0.465). In RAS/BRAF wild-type tumours, combination treatment was significantly superior to sequential therapy in all end-points.. In the overall population, XELAVIRI just missed to demonstrate the non-inferiority of sequential compared to combination therapy for TFS. However, the non-inferiority of sequential treatment was observed in elderly patients and RAS mutant tumours.. Trial registration ID (clinicaltrials.gov) NCT01249638.

Topics: Aged; Antimetabolites; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Humans; Irinotecan; Leucovorin; Randomized Controlled Trials as Topic; Rectal Neoplasms

The presence of mesorectal fascia (MRF) invasion, grade 4 extramural venous invasion (EMVI), tumour deposits (TD) or extensive or bilateral extramesorectal (lateral) lymph nodes (LLN) on MRI has been suggested to identify patients with indisputable, extensive locally advanced rectal cancer (LARC), at high risk of treatment failure. The aim of this study is to evaluate whether or not intensified chemotherapy prior to neoadjuvant chemoradiotherapy improves the complete response (CR) rate in these patients.. This multicentre, single-arm, open-label, phase II trial will include 128 patients with non-metastatic high-risk LARC (hr-LARC), fit for triplet chemotherapy. To ensure a study population with indisputable, unfavourable prognostic characteristics, hr-LARC is defined as LARC with on baseline MRI at least one of the following characteristics; MRF invasion, EMVI grade 4, enlarged bilateral or extensive LLN at high risk of an incomplete resection, or TD. Exclusion criteria are the presence of a homozygous DPD deficiency, distant metastases, any chemotherapy within the past 6 months, previous radiotherapy within the pelvic area precluding standard chemoradiotherapy, and any contraindication for the planned treatment. All patients will be planned for six two-weekly cycles of FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) prior to chemoradiotherapy (25 × 2 Gy or 28 × 1.8 Gy with concomitant capecitabine). A resection will be performed following radiological confirmation of resectable disease after the completion of chemoradiotherapy. A watch and wait strategy is allowed in case of a clinical complete response. The primary endpoint is the CR rate, described as a pathological CR or a sustained clinical CR one year after chemoradiotherapy. The main secondary objectives are long-term oncological outcomes, radiological and pathological response, the number of resections with clear margins, treatment-related toxicity, perioperative complications, health-related costs, and quality of life.. This trial protocol describes the MEND-IT study. The MEND-IT study aims to evaluate the CR rate after intensified chemotherapy prior to concomitant chemoradiotherapy in a homogeneous group of patients with locally advanced rectal cancer and indisputably unfavourable characteristics, defined as hr-LARC, in order to improve their prognosis.. Clinicaltrials.gov: NCT04838496 , registered on 02-04-2021 Netherlands Trial Register: NL9790.. Version 3 dd 11-4-2022.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemoradiotherapy; Clinical Trials, Phase II as Topic; Fluorouracil; Humans; Leucovorin; Multicenter Studies as Topic; Neoadjuvant Therapy; Neoplasm Staging; Neoplasms, Second Primary; Organoplatinum Compounds; Quality of Life; Rectal Neoplasms; Treatment Outcome

The addition of aflibercept to the fluorouracil and irinotecan (FOLFIRI) regimen significantly improved clinical outcomes in patients with metastatic colorectal cancer (CRC) previously treated with oxaliplatin. We aimed to investigate the efficacy and safety of second-line FOLFIRI and aflibercept combination in patients with metastatic CRC in real-life experience.. Four hundred and thirty-three patients who treated with FOLFIRI and aflibercept in the second-line were included in the study. The clinical and pathological features of the patients were recorded retrospectively. Survival (overall and progression-free survival [PFS]), response rates, and safety data were analyzed.. The median age was 61. Majority of patients (87.5%) received first-line bevacizumab and 10.1% of patients received anti-epidermal growth factor receptor agents. About 80% of patients had KRAS, 18.6% of patients had NRAS, and 6.4% of patients had BRAF mutations. The median OS was 11.6 months (95% confidence interval [CI], 10.6-12.6) and the median PFS was 6 months (95% CI, 5.5-6.5). About 4.6% of patients had complete response and 30.6% of patients had partial response as best tumor response. Grade 1-2 toxicities were seen in 33.4% of patients, while grade 3-4 toxicities were recorded in 27% of patients. Eight patients (2%) died due to treatment toxicity.. Overall and PFS were similar in routine clinical practice compared to phase III pivotal VELOUR trial. However, response rates were found to be higher. It was observed that there were fewer adverse events compared to the VELOUR trial.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Middle Aged; Rectal Neoplasms; Retrospective Studies

The chemotherapy exposure during chemoradiotherapy for rectal cancer is adequate for radiosensitization but suboptimal for treatment of distant micrometastasis. This study aimed to determine tolerability, dose intensity, response, and toxicity of a novel intensified neoadjuvant treatment approach.. Eligible patients were MRI-staged T3-4NxM0 rectal adenocarcinoma. Treatment consisted of FOLFOX chemotherapy given in weeks 1, 6, and 11 with pelvic radiotherapy (25.2 Gy in 3 weeks in 1.8 Gy/fraction with oxaliplatin and 5-FU continuous infusion) given in weeks 3-5, and weeks 8-10. Surgery was performed 4-6 weeks later. The primary endpoint was tolerability defined as the percentage of patients who were able to complete the planned treatment course. Survival rates were estimated using the Kaplan-Meier method.. Median age of the 40 patients was 61.5 years. Rectal MRI-stage was T3 in 88%. Overall, 95% completed the regimen. All patients received 50.4 Gy. Relative dose intensity (≥75%) was 92% and 98% for oxaliplatin and 5-FU, respectively. High grade toxicities included neutropenia (25% grade 3; 7.5% grade 4) and diarrhoea (10%). Pathologic CR rate was 20%. Median follow-up was 54 months. The 5-year overall survival, freedom from relapse, locoregional control, and freedom from distant metastasis of the cohort was 82%, 72%, 97% and 72%.. Delivery of intensified neoadjuvant treatment with interdigitating chemotherapy and radiotherapy is feasible with no increase in acute perioperative complications. A larger prospective study is required to further evaluate the potential survival benefit of this design.

Topics: Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Leucovorin; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Oxaliplatin; Prospective Studies; Rectal Neoplasms; Treatment Outcome

Preoperative chemoradiotherapy (CRT), the current standard of care for locally advanced rectal cancer (LARC), is associated with many radiotherapy (RT)-related side effects. We aimed to evaluate whether S-1 and oxaliplatin (SOX) or folinic acid, 5-FU, and oxaliplatin (mFOLFOX6) can be as effective as neoadjuvant chemotherapy (NAC) regimens for LARC without RT.. Patients with untreated resectable LARC were randomly assigned to receive SOX or mFOLFOX6. The NAC protocol period was 3 months. The primary endpoint was 3-year disease-free survival (DFS), and the secondary endpoints included pathological effects, surgical completion rate, 3-year survival, and safety.. From September 2013 to October 2015, 56 and 54 patients were enrolled in the SOX and mFOLFOX6 arms, respectively. The 3-year DFS rates were 69.4% (95% confidence interval [CI] 54.9-83.6) and 73.4% (95% CI 58.7-83.6) in the SOX and mFOLFOX6 arms, respectively; no significant differences were found between the arms (log-rank test; P = 0.5315, hazard ratio: 0.808, 95% CI 0.414-1.578). The 3-year survival rates were 92.3 and 91.8% in the SOX and mFOLFOX6 arms, respectively. The surgical completion rate was 98.1% overall, 100% in the SOX arm, and 96.0% in the mFOLFOX6 arm. The incidences of pathological response rates ≥grade 1b were 41.5 and 43.8% in the SOX and mFOLFOX6 arms, respectively. Both treatments were manageable and tolerable.. We demonstrated the effectiveness and safety of SOX and mFOLFOX6, both of which may be new neoadjuvant treatment candidates in previously untreated LARC cases.. Date of enrolment of the first participant to the trial: 3rd Oct 2013; This study was registered in the UMIN clinical trials registry on 14th Aug, 2013. (Prospectively registered, UMIN-CTR number UMIN000011486). https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&recptno=R000013441&language=J.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Drug Combinations; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Oxaliplatin; Oxonic Acid; Prognosis; Rectal Neoplasms; Survival Rate; Tegafur

We assessed the efficacy and safety of total neoadjuvant therapy, including targeted agent plus FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) induction chemotherapy followed by intensified chemoradiotherapy (CRT) and surgical resection, in patients with locally advanced rectal cancer.. This was a single-arm, single-centre phase II trial. Eligible patients had non-metastatic locally advanced rectal adenocarcinoma. Based on Ras-BRAF status, patients were treated with bevacizumab (mutated Ras-BRAF) or panitumumab/cetuximab (wild-type Ras-BRAF) plus FOLFOXIRI regimen followed by oxaliplatin-5-fluorouracil-based CRT and surgery. The primary end point was pathological complete response rate. Secondary end points were toxicity, compliance, tumour downstaging, complete resection, surgical complications, local and distant failures and overall survival. The sample size was planned to expect an absolute 20% improvement in pathological complete response rate over historical literature data with an α error of 0.05 and a power of 80%.. Between October 2015 and September 2019, 28 patients (median age 66 years) were enrolled. All patients had regional lymph node involvement at diagnosis. FOLFOXIRI plus bevacizumab was administered in 11 mutated Ras-BRAF patients, whereas the 17 wild-type Ras-BRAF patients received FOLFOXIRI plus panitumumab/cetuximab. Overall, total neoadjuvant therapy was well tolerated and 26 patients (92.9%) completed the programmed strategy. A complete response was achieved in nine cases (32.1%) and a nearly pathological complete response (ypT1 ypN0) in two patients (7.2%). There was no evidence of febrile neutropenia and no grade 4 adverse events were recorded. Radical resection was achieved in all cases.. FOLFOXIRI plus targeted agent-based induction chemotherapy and intensified CRT before surgery showed promising clinical activity and was well tolerated in locally advanced rectal cancer patients. This phase II trial provides a strong rationale for phase III studies.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Leucovorin; Neoadjuvant Therapy; Rectal Neoplasms

The aim of this study was to evaluate the effect of the interval between CRT and surgery on radiation proctitis, the pathologic response, and postoperative morbidity.. This was a cohort study from a phase III, randomized controlled trial (FOWARC study, NCT01211210). Data were retrieved from the leading center of the trial. Patients were divided into the short-interval (≤7 weeks) group and the long-interval (>7 weeks) group. The rate of radiation proctitis, pathologic complete regression (pCR) and morbidities were calculated for each group. Multivariate analysis was used to verify the impact of interval on radiation proctitis.. Surgery was performed in 60 patients after an interval of ≤7 weeks and in 97 patients after an interval of >7 weeks. The two groups according to interval were comparable in terms of baseline demographic and clinicotherapeutic characteristics. Radiation proctitis was identified by imaging in 9 (15.0%) patients in short-interval group and in 31 (32.0%) patients in long-interval group (P = .018). Multivariate analysis confirmed the correlation between long interval and radiation proctitis (P = .018). The long interval was significantly associated with longer median operation time compared to the short interval (P = .022). The rates of pCR and postoperative complications were not different between two groups.. A longer interval after CRT may be associated with higher rate of radiation proctitis and longer operation time. Moreover it did not increase the rate of pCR.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Cohort Studies; Dose Fractionation, Radiation; Female; Fluorouracil; Humans; Intestinal Mucosa; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Proctectomy; Proctitis; Radiation Injuries; Rectal Neoplasms; Rectum; Time Factors; Time-to-Treatment; Treatment Outcome

The addition of bevacizumab to chemotherapy improved outcomes for patients with metastatic colon cancer. E5204 was designed to test whether the addition of bevacizumab to mFOLFOX6, following neoadjuvant chemoradiation and definitive surgery, could improve overall survival (OS) in patients with stage II/III adenocarcinoma of the rectum.. Patients with stage II/III rectal cancer who had completed neoadjuvant 5-fluorouracil-based chemoradiation and had undergone complete resection were enrolled. Patients were randomized to mFOLFOX6 (Arm A) or mFOLFOX6 with bevacizumab (Arm B) administered every 2 weeks for 12 cycles.. E5204 registered only 355 patients (17% of planned accrual goal) as it was terminated prematurely owing to poor accrual. At a median follow-up of 72 months, there was no difference in 5-year overall survival (88.3% vs. 83.7%) or 5-year disease-free survival (71.2% vs. 76.5%) between the two arms. The rate of treatment-related grade ≥ 3 adverse events (AEs) was 68.8% on Arm A and 70.7% on Arm B. Arm B had a higher proportion of patients who discontinued therapy early as a result of AEs and patient withdrawal than did Arm A (32.4% vs. 21.5%, p = .029).The most common grade 3-4 treatment-related AEs were neutropenia, leukopenia, neuropathy, diarrhea (without prior colostomy), and fatigue.. At 17% of its planned accrual, E5204 did not meet its primary endpoint. The addition of bevacizumab to FOLFOX6 in the adjuvant setting did not significantly improve OS in patients with stage II/III rectal cancer.. At 17% of its planned accrual, E5204 was terminated early owing to poor accrual. At a median follow-up of 72 months, there was no significant difference in 5-year overall survival (88.3% vs. 83.7%) or in 5-year disease-free survival (71.2% vs. 76.5%) between the two arms. Despite significant advances in the treatment of rectal cancer, especially in improving local control rates, the risk of distant metastases and the need to further improve quality of life remain a challenge. Strategies combining novel agents with chemoradiation to improve both distant and local control are needed.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Chemotherapy, Adjuvant; Disease-Free Survival; Fluorouracil; Humans; Leucovorin; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Quality of Life; Rectal Neoplasms

Preoperative chemoradiotherapy (PCRT) followed by surgery and adjuvant chemotherapy is the current standard treatment for stage II/III rectal cancer. However, radiotherapy in the pelvic area is commonly associated with complications such as anastomotic leakage, sexual dysfunction, and fecal incontinence. Recently, the MERCURY study showed that preoperative high-resolution magnetic resonance imaging (MRI) helped to selectively avoid PCRT. It remains unclear whether PCRT is necessary in patients who can achieve a negative circumferential resection margin (CRM) with surgery alone and in patients with cT. This study, named TME-FOLFOX, is a prospective, open-label, multicenter, phase II randomized trial. Patients with locally advanced rectal cancer will be randomized to receive PCRT followed by TME and adjuvant chemotherapy (arm A) or upfront radical surgery with TME followed by adjuvant FOLFOX chemotherapy (arm B). Clinical stage II/III rectal cancer without CRM involvement and lateral lymph node metastasis will be defined using preoperative MRI. The primary endpoint is 3-year disease-free survival (DFS). Secondary endpoints include 5-year DFS, local recurrence rate, systemic recurrence rate, cost-effectiveness, and overall survival. We hypothesized that our experimental group (arm B) will have a 3-year DFS of 75% and a non-inferiority margin of 15%.. Identifying whether patients require PCRT is one of the critical issues in locally advanced rectal cancer. This study aims to elucidate whether PCRT may not be required for all patients with stage II/III rectal cancer, especially for the MRI-based intermediate-risk group (with cT. ClinicalTrials.gov, NCT02167321. Registered on 19 June 2014.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Chemotherapy, Adjuvant; Clinical Trials, Phase II as Topic; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Fluorouracil; Humans; Leucovorin; Multicenter Studies as Topic; Neoadjuvant Therapy; Neoplasm Invasiveness; Neoplasm Staging; Organoplatinum Compounds; Preoperative Care; Prognosis; Prospective Studies; Randomized Controlled Trials as Topic; Rectal Neoplasms; Republic of Korea; Survival Analysis; Treatment Outcome

Preoperative radiochemotherapy (RCT) is recommended in France prior to total mesorectal excision in patients with mid or low locally advanced rectal cancer (LARC) (cT3/T4 and/or N+) because it has been shown to improve local control. Preoperative RCT has also disadvantages including the absence of proven impact on metastatic recurrence and the risk of late side effects on bowel and genitourinary function. In patients with primarily resectable LARC, preoperative systemic chemotherapy without pelvic irradiation could be used as an alternative to RCT.. This study is a multicenter, open-label randomized, 2-arm phase III non-inferiority trial. Patients with mid or low resectable LARC (cT3N0 or cT1-T3N+ with circumferential resection margin [CRM] > 2 mm on pretreatment MRI) will be randomized to either modified FOLFIRINOX for 3 months or RCT (Cap50 intensified-modulated radiotherapy). All patients have restaging MRI after preoperative treatment. The primary endpoint is 3-year progression-free survival (PFS) from the time to randomization including progression during preoperative treatment. Secondary endpoints are treatment related toxicity, treatment compliance, R0 resection rate, sphincter saving surgery rate, postoperative morbidity and mortality rates, loco-regional recurrence free survival, overall survival, bowel and sexual functions at diagnosis, quality of life, radiologic and pathologic response after preoperative treatment. The number of patients required is 574.. The choice of modified FOLFIRINOX for preoperative chemotherapy is supported by recent and consistent data on safety and efficacy of this regimen on rectal cancer. The use of preoperative chemotherapy instead of RCT could be associated with pronounced advantages in terms of functional results and quality of life in cancer survivors. However and first of all, the non-inferiority of preoperative chemotherapy compared to RCT on oncologic outcome has to be validated. If this study demonstrates the non-inferiority of chemotherapy compared to RCT, this can lead to a crucial change in clinical practice in a large subset of rectal cancer patients.. ClinicalTrials.gov NCT03875781 (March 15, 2019). Version 1.1.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Chemotherapy, Adjuvant; Clinical Trials, Phase III as Topic; Disease-Free Survival; Drug Administration Schedule; Equivalence Trials as Topic; Female; Fluorouracil; Follow-Up Studies; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Multicenter Studies as Topic; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Oxaliplatin; Patient Compliance; Postoperative Complications; Preoperative Period; Proctectomy; Progression-Free Survival; Quality of Life; Randomized Controlled Trials as Topic; Rectal Neoplasms; Rectum

Neoadjuvant concomitant chemoradiotherapy followed by surgical resection is the standard of care in the treatment of rectal cancer. We are investigating the value of adding combination chemotherapy oxaliplatin, irinotecan, leucovorin and fluorouracil (FOLFIRINOX) before neoadjuvant chemoradiotherapy.. Forty-one patients with middle and lower rectal cancer were included. FOLFORINOX were given every 2 weeks over 2 months (4 cycles) followed by concomitant chemoradiotherapy (CRT). Surgery was done 6-8 weeks after CRT and then adjuvant 4 months of FOLFOX or XELOX were given. The primary end point was sphincter preservation rate.. All patients received the four cycles of neoadjuvant chemotherapy FOLFORINOX, 38 patients completed CRT and only 29 patients underwent surgery. 32 patients were available for assessment (29 patients who underwent surgery and three patients who refuse surgery because of no evidence of disease by endoscopy, imaging and biopsy). Sphincter preservation was achieved in twenty-one patients (51.2%). Pathological complete response rate was 24.1%. After a median follow up of 24 months. Median PFS was 20 months and 2-years PFS was 62.3%. The median overall survival of all patients was not reached, while 2-years OS was 76.5%.. Neoadjuvant FOLFIRINOX followed by CRT for middle and lower rectal cancer is feasible, tolerable with satisfactory sphincter preservation rate. 
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Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Deoxycytidine; Female; Fluorouracil; Follow-Up Studies; Humans; Irinotecan; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Oxaliplatin; Prognosis; Prospective Studies; Rectal Neoplasms; Survival Rate; Young Adult

The present study evaluated the safety and efficacy of neoadjuvant chemotherapy with modified 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus panitumumab in clinical stage III rectal cancer with KRAS wild-type.. We conducted a prospective multicenter phase II trial. KRAS wild-type clinical stage III rectal cancer patients were enrolled. Patients received 6 cycles of mFOLFOX6 with 6 mg/kg panitumumab as neoadjuvant chemotherapy. The primary outcome was the response rate (RR) defined by RECIST. Lateral lymph node dissection (LLDN) was performed when patients had a locally advanced tumor < 9 cm from the anal margin.. A total of 50 patients were enrolled. Twelve (24.0%) experienced grade 3-4 adverse events during neoadjuvant chemotherapy. The RR was 88.0% (complete response 2.0%, partial response 86.0%), which met the primary outcome. All patients underwent laparoscopic surgery and achieved R0 resection. Seven patients underwent resection of other adjacent organs, and 43 underwent LLND. Twelve patients (24.0%) experienced grade 3-4 postoperative complications, and 4 (8.0%) had pathological complete response (pCR). Thirteen patients (26.0%) had lymph node metastasis. Forty-five patients (90.0%) received postoperative adjuvant chemotherapy. The 3-year relapse-free survival (RFS) and overall survival (OS) rates were 79.0% and 93.7%, respectively.. Neoadjuvant chemotherapy of mFOLFOX6 plus panitumumab without radiotherapy resulted in a low pCR rate but a high PR rate, low local recurrence rate, and good long-term outcome, suggesting that this treatment strategy may be a viable option for patients unable or unwilling to receive radiotherapy. The trial was registered with the UMIN Clinical Trials Registry, number 000006039.

Topics: Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Leucovorin; Neoadjuvant Therapy; Neoplasm Staging; Panitumumab; Prospective Studies; Rectal Neoplasms; Treatment Outcome

Current standard practice for locally advanced rectal cancer (LARC) entails a multidisciplinary approach that includes preoperative chemoradiotherapy, followed by total mesorectal excision, and then adjuvant chemotherapy. The latter has been accompanied by low compliance rates and no survival benefit in phase III randomized trials, so the strategy of administering neoadjuvant, rather than adjuvant, chemotherapy has been adapted by many trials, with improvement in pathologic complete response. Induction chemotherapy with oxaliplatin has been shown to have increased efficacy in rectal cancer, while short-course radiation therapy with consolidation chemotherapy increased short-term overall survival rate and decreased toxicity levels, making it cheaper and more convenient than long-course radiation therapy. This led to recognition of total neoadjuvant therapy as a valid treatment approach in many guidelines despite limited available survival data. With the upregulation (PDL-1) expression in rectal tumors after radiotherapy and the increased use of in malignant melanoma, the novel approach of combining immunotherapy with chemotherapy after radiation may have a role in further increasing pCR and improving overall outcomes in rectal cancer.. The study is an open label single arm multi- center phase II trial. Forty-four recruited LARC patients will receive 5Gy x 5fractions of SCRT, followed by 6 cycles of mFOLFOX-6 plus avelumab, before TME is performed. The hypothesis is that the addition of avelumab to mFOLFOX-6, administered following SCRT, will improve pCR and overall outcomes. The primary outcome measure is the proportion of patients who achieve a pCR, defined as no viable tumor cells on the excised specimen. Secondary objectives are to evaluate 3-year progression-free survival, tumor response to treatment (tumor regression grades 0 & 1), density of tumor-infiltrating lymphocytes, correlation of baseline Immunoscore with pCR rates and changes in PD-L1 expression.. Recent studies show an increase in PD-L1 expression and density of CD8+ TILs after CRT in rectal cancer patients, implying a potential role for combinatory strategies using PD-L1- and programmed-death- 1 inhibiting drugs. We aim through this study to evaluate pCR following SCRT, followed by mFOLFOX-6 with avelumab, and then TME procedure in patients with LARC.. Trial Registration Number and Date of Registration: ClinicalTrials.gov NCT03503630, April 20, 2018.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials, Phase II as Topic; Female; Fluorouracil; Follow-Up Studies; Humans; Immunotherapy; Leucovorin; Male; Middle Aged; Multicenter Studies as Topic; Neoadjuvant Therapy; Organoplatinum Compounds; Progression-Free Survival; Prospective Studies; Rectal Neoplasms; Young Adult

Neoadjuvant chemotherapy and short-course radiotherapy followed by resection has been gaining recognition in the treatment of rectal cancer. Avelumab is a fully human immunoglobulin that binds Programmed Death-Ligand 1 (PD-L1) and prevents the suppression of the cytotoxic T cell immune response. This phase II trial evaluates the safety and pathologic response rate of short-course radiation followed by 6 cycles of mFOLFOX6 with avelumab in patients with locally advanced rectal cancer (LARC).. This study is prospective single-arm, multicenter phase II trial adopting Simon's two-stage. Short-course radiation is given over 5 fractions to a total dose of 25 Gy. mFOLFOX6 plus avelumab (10 mg/kg) are given every 2 weeks for 6 cycles. Total mesorectal excision is performed 3-4 weeks after the last cycle of avelumab. Follow up after surgery is done every 3 months to a total of 36 months. Adverse event data collection is recorded at every visit.. 13 out of 44 patients with LARC were enrolled in the first stage of the study (30% from total sample size). All patients met the inclusion criteria and received the full short-course radiation course followed by 6 cycles of mFOLFOX6 plus avelumab. 12 out of the 13 patients completed TME while one patient had progression of disease and was dropped out of the study. The sample consisted of 9 (69%) males and 4 (31%) females with median age of 62 (33-73) years. The first interim analysis revealed that 3 (25%) patients achieved pathologic complete response (pCR) (tumor regression grade, TRG 0) out of 12. While 3 (25%) patients had near pCR with TRG 1. In total, 6 out of 12 patients (50%) had a major pathologic response. All patients were found to be MMR proficient. The protocol regimen was well tolerated with no serious adverse events of grade 4 reported.. In patients with LARC, neoadjuvant radiation followed by mFOLFOX6 with avelumab is safe with a promising pathologic response rate. Trial Registration Number and Date of Registration ClinicalTrials.gov NCT03503630, April 20, 2018. https://clinicaltrials.gov/ct2/show/NCT03503630?term=NCT03503630&draw=2&rank=1 .

Topics: Adenocarcinoma; Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Female; Fluorouracil; Humans; Immunotherapy; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Prospective Studies; Rectal Neoplasms; Treatment Outcome

There is continued debate regarding the optimal combinations of radiation therapy and chemotherapy in the preoperative treatment of locally advanced rectal adenocarcinomas. We report our single-institution experience of feasibility and early oncologic outcomes of short-course preoperative radiation therapy (5 Gy X 5 fractions) followed by consolidation neoadjuvant chemotherapy.. We reviewed the records of 26 patients with locally advanced rectal adenocarcinoma. All patients underwent short course radiotherapy (5 Gy X 5 fractions) followed by chemotherapy [either modified infusional and bolus 5-fluorouracail and oxalipatin (mFOLFOX6) or capecitabine and oxaliplatin] prior to consideration for surgery. A full course of chemotherapy was defined as at least 8 weeks of chemotherapy.. There were five clinical (c) T2, 16 cT3, and five cT4 rectal tumors, with 88% cN+. Twenty-five patients received a median of 4 cycles (range 3 to 8) of mFOLFOX6 (with one cycle defined as a two-week period); one patient received 3 cycles of capecitabine and oxaliplatin. All patients completed SCRT; 81% completed the full course of neoadjuvant chemotherapy with 19% requiring dose reductions in chemotherapy, most commonly due to neuropathy. Nineteen patients underwent post-treatment endoscopic evaluation, and nine patients were noted to achieve a complete clinical response (CCR). Six of the nine patients who achieved CCR opted for a non-operative approach of watch-and-wait. Twenty patients underwent surgical resection; pathologic complete response was observed in seven (35%) of these twenty. The main radiation-associated toxicity was proctitis with CTCAE Grade 2 proctitis observed in seven patients (27%). Post-operative Clavien-Dindo Grade 3 complications within 30 days of surgery were identified in six patients (30%), with no Grade 4 or 5 adverse events. Median length of hospital stay was 4.5 days (range 2-16 days); three patients were readmitted within a 30 day period.. Short course preoperative radiotherapy followed by neoadjuvant chemotherapy was well-tolerated and achieved oncologic outcomes that compare favorably with short-course radiation therapy alone or long-course chemoradiotherapy. This regimen is associated with high rates of clinical and pathologic complete response.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemoradiotherapy, Adjuvant; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Oxaliplatin; Rectal Neoplasms; Retrospective Studies; Treatment Outcome

Tailored neoadjuvant treatment of locally advanced rectal cancer (LARC) may improve outcomes. The aim of this study was to determine early MRI prognostic parameters with which to stratify neoadjuvant treatment in patients with LARC.. All patients from a prospective, phase II, multicentre randomized study (GRECCAR4; NCT01333709) were included, and underwent rectal MRI before treatment, 4 weeks after induction chemotherapy and after completion of chemoradiotherapy (CRT). Tumour volumetry, MRI tumour regression grade (mrTRG), T and N categories, circumferential resection margin (CRM) status and extramural vascular invasion identified by MRI (mrEMVI) were evaluated.. A total of 133 randomized patients were analysed. Median follow-up was 41·4 (95 per cent c.i. 36·6 to 45·2) months. Thirty-one patients (23·3 per cent) developed tumour recurrence. In univariable analysis, mrEMVI at baseline was the only prognostic factor associated with poorer outcome (P = 0·015). After induction chemotherapy, a larger tumour volume on MRI (P = 0·019), tumour volume regression of 60 per cent or less (P = 0·002), involvement of the CRM (P = 0·037), mrEMVI (P = 0·026) and a poor mrTRG (P = 0·023) were associated with poor outcome. After completion of CRT, the absence of complete response on MRI (P = 0·004), mrEMVI (P = 0·038) and a poor mrTRG (P = 0·005) were associated with shorter disease-free survival. A final multivariable model including all significant variables (baseline, after induction, after CRT) revealed that Eastern Cooperative Oncology Group performance status (P = 0·011), sphincter involvement (P = 0·009), mrEMVI at baseline (P = 0·002) and early tumour volume regression of 60 per cent or less after induction (P = 0·007) were associated with relapse.. Baseline and early post-treatment MRI parameters are associated with prognosis in LARC. Future preoperative treatment should stratify treatment according to baseline mrEMVI status and early tumour volume regression.. El tratamiento neoadyuvante personalizado del cáncer de recto localmente avanzado (locally advanced rectal cancer, LARC) puede mejorar los resultados. El objetivo de este estudio fue determinar factores pronósticos precoces mediante RMN para estratificar el tratamiento neoadyuvante en pacientes con LARC. MÉTODOS: Todos los pacientes de un eensayo prospectivo de fase II, multicéntrico y aleatorizado (GRECCAR4-NCT01333709) se incluyeron en este estudio y se les realizó una RMN antes del tratamiento, 4 semanas después de la quimioterapia de inducción y después de completar la quimiorradioterapia (chemoradiation, CRT). Se evaluó la volumetría tumoral, el grado de regresión tumoral mediante RMN (MRI Tumor Regression Grade, mrTRG), la estadificación T, la estadificación N, el estado del margen de resección circunferencial (circumferential resection margin, CRM) y la presencia de invasión extramural vascular en la RMN (extramural vascular invasion, mrEMVI).. Se analizaron 133 pacientes aleatorizados. La mediana de seguimiento fue de 41,4 meses (i.c. del 95%: 36,6-45,2). En 31 pacientes (23%) se diagnosticó una recidiva. En el análisis univariado de la situación basal, mrEMVI fue el único factor pronóstico asociado con un peor resultado (P = 0,0152). Después de la quimioterapia de inducción, un volumen tumoral más alto en la RMN (P = 0,019), una regresión del volumen tumoral ≤ 60% (P = 0,002), la afectación del CRM (P = 0,037), mrEMVI (P = 0,026) y un grado escaso mrTRG (P = 0,023) se asociaron con un mal resultado. Después de completar la CRT, la ausencia de respuesta completa en la RMN (P = 0,004), la presencia de mrEMVI (P = 0,04) y una insuficiente mrTRG (P = 0,005) se asociaron con una supervivencia libre de enfermedad más corta. En el modelo multivariable final en el que se incluyeron todas las variables significativas (basales, postinducción, post-CRT), el estado de ECOG (P = 0,011), la afectación esfinteriana (P = 0,009), la presencia de EMVI al inicio (P = 0,002) y una regresión precoz del volumen tumoral ≤ 60% después de la inducción (P = 0,007) se asociaron con una recidiva. CONCLUSIÓN: Los parámetros basales y post-tratamiento precoces de la RMN se asocian con el pronóstico en el LARC. La estrategia terapéutica preoperatoria futura deberá estratificar el tratamiento de acuerdo con la presencia de EMVI al inicio y la regresión precoz del volumen tumoral.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Disease-Free Survival; Drug Administration Schedule; Fluorouracil; Humans; Infusions, Intravenous; Irinotecan; Laparoscopy; Leucovorin; Magnetic Resonance Imaging; Middle Aged; Neoplasm Recurrence, Local; Oxaliplatin; Precision Medicine; Prospective Studies; Rectal Neoplasms; Robotic Surgical Procedures; Tumor Burden; Young Adult

Patients affected with Stage IV colorectal cancer and unresectable metastases represent a heterogeneous group. Resection of the primary tumor or stent positioning followed by chemotherapy and/or targeted therapies still represent a difficult choice for surgeons.. From February 2013 to September 2019, 46 patients were enrolled into a prospective randomized open label parallel trial presenting with Stage IVA and IVB rectal cancer, unresectable metastases and symptoms of subacute large bowel obstruction. Our population was divided into two groups: Group 1 included 20 patients who underwent placement of a self-expandable metal stent and Group 2 included 26 patients in whom primary tumor resection was performed.. One-year actuarial survival rate of Group 1 was significantly lower compared to Group 2. Overall 17 patients had survival longer than 1-year (3 in Group 1 and 14 in Group 2). Cox regression analysis showed that endoscopic stent positioning and the suspension of the chemotherapy because of deterioration of liver function tests were the two most important factors negatively influencing survival.. Patients affected with stage IVA and IVB rectal cancer and symptoms of bowel obstruction had a significant longer survival rate when submitted to surgical rectal resection followed by chemotherapy.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Combined Modality Therapy; Female; Fluorouracil; Humans; Intestinal Obstruction; Leucovorin; Male; Middle Aged; Molecular Targeted Therapy; Organoplatinum Compounds; Prospective Studies; Rectal Neoplasms; Self Expandable Metallic Stents; Survival Rate

More than half of the 40,000 incident rectal cancer patients in the United States each year are diagnosed at clinical stage II and III (locally advanced stage). For this group, high rates of cure can be achieved with the combination of pelvic radiation and sensitizing 5-fluorouracil (chemoradiation), surgery and chemotherapy, but treatment is long, arduous and toxicities are substantial. The PROSPECT trial (N1048, NCT01515787) was designed to determine whether neoadjuvant chemotherapy with 5-fluorouracil and oxaliplatin (FOLFOX) could be used as an alternative to neoadjuvant chemoradiation without compromising treatment outcomes and to spare these patients excess toxicity. The statistical design balanced the twin co-primary goals of achieving low local and distant recurrence rates. Study design features contended with the need for stringent safeguards given limited phase II data, the need for straightforward criteria to facilitate both accrual and protocol fidelity and the importance of patients' perspectives on symptom burden and treatment toxicity.. PROSPECT is an ongoing multi-site two-group seamless phase II/III randomized trial comparing standard neoadjuvant chemoradiation versus neoadjuvant chemotherapy with selective use of chemoradiation for patients with locally advanced rectal cancer. Challenges addressed in the design and conduct of PROSPECT have included the following: (1) setting safety thresholds given limited single-center phase II data, (2) establishing workable eligibility criteria, (3) balancing competing time to local and distant recurrence as co-primary endpoints and (4) obtaining reliable and complete data for patients' symptom burden. The design and implementation challenges, choices, modifications and their implications for the design of future national cooperative group clinical trials are presented.. PROSPECT incorporated stringent thresholds for both complete surgical resection (R0) and the time to local recurrence as early stopping rules. When predetermined stopping criteria were not met after evaluation of the first 366 participants in the randomized phase II, the study transitioned seamlessly to phase III with cumulative accrual of over 1000 participants. Eligibility criteria stipulating rectal tumor location based on distance from the anal verge were unworkable, and the protocol was amended to a more pragmatic approach that assigned surgeons with primary responsibility for determining eligibility. Central radiology review was feasible and in some cases prompted discontinuation of protocol treatment. Participation in toxicity reporting using the National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events was uniformly high and was well accepted by participants from over 200 sites in the United States, Canada and Switzerland.. The strategies used to overcome these obstacles may inform the design of other studies that involve multi-modality treatment interventions, particularly trials where implementation of consistent criteria for eligibility and outcomes across hundreds of practice settings is necessary.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Chemotherapy, Adjuvant; Disease-Free Survival; Fluorouracil; Humans; Leucovorin; Neoplasm Recurrence, Local; Neoplasm Staging; Organoplatinum Compounds; Rectal Neoplasms

Neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) does not achieve effective control of distant metastases. Induction chemotherapy is a promising strategy, and bevacizumab (BV) could improve the results of CRT. 5-Fluorouracil, oxaliplatin and irinotecan (FOLFOXIRI) plus BV is a treatment option in metastatic colorectal cancer. We evaluate feasibility and efficacy of neoadjuvant treatment comprising induction FOLFOXIRI plus BV followed by CRT with fluoropyrimidines plus BV.. In this phase II single-arm trial, patients node-positive or clinical T4 or high-risk T3 LARC underwent 6 cycles of induction FOLFOXIRI plus BV, followed by CRT (50.4 Gy plus concomitant capecitabine) and BV (5 mg/kg on days 1, 15 and 28). Surgery was planned 8 weeks after completion of CRT. Primary end-point was 2-year disease-free survival (DFS).. We enrolled 49 patients: All but one (withdrewing consent after enrolment) were included in the per-protocol analyses. The study met its primary end-point: 36 patients were free of recurrence at 2 years (2-y DFS: 80.45%, 95% confidence interval [CI]: 78.79-82.10). Forty-four patients underwent surgery; pathologic complete response rate was 36.4%. Forty-six patients completed induction: neutropenia (41.6%) and diarrhoea (12.5%) were main G3/4 toxicities. Forty-five patients received CRT, but the protocol was amended and the capecitabine schedule during CRT was slightly modified after 13 patients due to the incidence of G3 hand-foot syndrome and proctitis (23.1%). After amendment, no severe events during CRT were reported.. FOLFOXIRI plus BV followed by CRT plus BV is feasible and active. Results in terms of DFS suggest that this strategy may improve distant disease control in LARC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Chemoradiotherapy; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Rectal Neoplasms; Treatment Outcome

The aim of this study was to assess the safety of rectal surgery after 5-fluorouracil-leucovorin-oxaliplatin chemotherapy (FOLFOX6).. This was a prospective, multicenter study in 11 Japanese hospitals. We included patients with rectal cancer who received 4 courses of modified FOLFOX6 (mFOLFOX6) before rectal surgery and examined the postoperative complication rate, the clinicopathological response, and the rate of chemotherapy-related adverse events (UMIN 000012559).. The study population included 36 men and 5 women. The average age of the patients was 60.8 years and the average body mass index was 23.1 kg/m. Surgery after four courses of mFOLFOX6 chemotherapy can be a safe and promising strategy for patients with locally advanced rectal cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Digestive System Surgical Procedures; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Preoperative Care; Prospective Studies; Rectal Neoplasms; Safety; Treatment Outcome; Young Adult

Preoperative radiotherapy followed by total mesorectal excision with adjuvant chemotherapy has been recommended as the preferred treatment method for locally advanced rectal cancer (LARC). Similar rates of local control, survival and toxicity were observed in preoperative long-course chemoradiotherapy (LCRT) (45-50.4 Gy in 25-28 fractions) and in short-course radiotherapy (SCRT) with 25 Gy over five fractions. Both regimens lower the local recurrence rates compared with that of surgery followed by postoperative radiotherapy. With the simplicity and lower cost of SCRT, a growing number of patients have been receiving SCRT as preoperative radiotherapy. However, the currently established SCRT (25 Gy over five fractions) followed immediately by surgery resulted in poor downstaging and sphincter preservation rate. The pathological complete response (pCR) rate is also markedly lower with SCRT than with LCRT (0.7%vs16%). Several studies recommended SCRT with delayed surgery for more than 4 weeks with expectation of improved pathological outcomes and fewer postoperative complications. While a number of clinical trials demonstrated a persistently better overall local control with SCRT than with LCRT, overall survival advantage has not been observed. Since survival is mainly depended on distant metastases, efforts should be made towards more effective pathological response and systemic treatment. Given the apparent advantages of SCRT, we aimed to establish a dose escalation of SCRT and sequential modified FOLFOX6 (mFOLFOX6) as preoperative therapy for LARC with objectives of achieving an optimal balance of safety, cost effectiveness and clinical outcome, and to support further investigation of this regimen in a phase II/III setting.. In this phase I study, three dose levels (6Gy×5F, 7Gy×5F, 8Gy×5F to gross tumour volume, while keeping the rest of irradiated volume at 5Gy×5) of SCRT followed by four cycles of mFOLFOX6 chemotherapy as neoadjuvant therapy will be tested by using the traditional 3+3 design. The pCR rate, R0 resection rate, sphincter preservation rate and treatment related toxicity will be assessed.. The study protocol was approved by the Ethics Committee of Fujian Medical University Union Hospital (No. 2017YF020-02) and all participants provided written informed consent. Results from our study will be disseminated in international peer-reviewed journals. All study procedures were developed in order to assure data protection and confidentiality.. NCT03466424; Pre-results.

Topics: Antineoplastic Combined Chemotherapy Protocols; Clinical Trials, Phase I as Topic; Fluorouracil; Humans; Leucovorin; Neoadjuvant Therapy; Observational Studies as Topic; Organoplatinum Compounds; Patient Outcome Assessment; Patient Selection; Preoperative Care; Radiotherapy Dosage; Rectal Neoplasms

The aim of this study is to evaluate the safety and efficacy of induction modified 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus bevacizumab followed by S- 1-based chemoradiotherapy in magnetic resonance imaging (MRI)-defined poor-risk locally advanced low rectal cancer.. A total of 43 patients were enrolled. Grade 3-4 adverse events occurred in nine patients during induction chemotherapy and in five patients during chemoradiotherapy. One patient declined surgery with a clinical complete response. Forty-two patients underwent surgery, and 16 had pCR [37.2%, 95% confidence interval (CI) 24.4-52.1%]. All underwent R0 resection without conversion, including combined resection of adjacent structures (n = 14) and lateral node dissection (n = 30). Clavien-Dindo grade 3-4 complications occurred in six patients (14.3%). With median follow-up of 52 months, six developed recurrences (lung n = 5, local n = 1; 3-year relapse-free survival 86.0%).. This study achieved a high pCR rate with favorable toxicity and postoperative complications in poor-risk locally advanced low rectal cancer. Multicenter study is warranted to evaluate this regimen.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Capecitabine; Chemoradiotherapy, Adjuvant; Combined Modality Therapy; Female; Fluorouracil; Follow-Up Studies; Humans; Laparoscopy; Leucovorin; Lymph Node Excision; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Oxaliplatin; Prognosis; Prospective Studies; Rectal Neoplasms; Survival Rate

This trial evaluated whether preoperative short-course radiotherapy and consolidation chemotherapy (CCT) were superior to chemoradiation in rectal cancers with clinical (c)T4 or fixed cT3. Previously, we reported early results showing no differences in the radical surgery rate (primary end point). In the short-course/CCT group, we observed lower acute toxicity of preoperative treatment and better overall survival (OS). We updated results to determine whether the benefit in OS was sustained and to evaluate late complications.. Patients with cT4 or fixed cT3 rectal cancer were randomized either to preoperative 5 × 5 Gy and three cycles of FOLFOX4 or to chemoradiation (50.4 Gy with bolus 5-Fu, leucovorin and oxaliplatin).. Patients (N = 515) were eligible for analysis, 261 in the short-course/CCT group and 254 in the chemoradiation group. The median follow-up was 7.0 years. The difference in OS was insignificant [hazard ratio (HR) 0.90; 95% confidence interval (CI) 0.70-1.15; P = 0.38). However, the difference in early OS favouring short-course/CCT previously reported was observed again, being 9% at 3 years (95% CI 0.5% to 17%). This difference disappeared later; at 8 years OS was 49% in both groups. There was no difference in disease-free survival (HR 0.95; 95% CI 0.75-1.19; P = 0.65) at 8 years 43% versus 41% in the short-course/CCT group versus the chemoradiation group, respectively. The corresponding values for cumulative incidences of local failure and distant metastases did not differ and were HR = 1.08, 95% CI 0.70-1.23, P = 0.60, 35% versus 32% and HR = 1.10, 95% CI 0.68-1.23, P = 0.54, 36% versus 34%, respectively. The rate of late complications was similar (P = 0.66), grade 3+ being 11% versus 9% in the short-course/CCT group versus the chemoradiation group, respectively.. The superiority of preoperative short-course/CCT over chemoradiation was not demonstrated.. The trial is registered as ClinicalTrials.gov number NCT00833131.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Consolidation Chemotherapy; Disease-Free Survival; Dose Fractionation, Radiation; Female; Fluorouracil; Follow-Up Studies; Humans; Incidence; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Organoplatinum Compounds; Poland; Proctectomy; Rectal Neoplasms; Rectum; Time Factors; Young Adult

To evaluate the cost-effectiveness of preoperative short-course radiotherapy (SCRT, 5 × 5 Gy) plus FOLFOX4 versus long-course oxaliplatin and bolus of fluorouracil based preoperative long-course chemoradiotherapy (LCCRT, 50.4 Gy in 28 fractions) in the management of cT4 or advanced cT3 rectal cancer (RC), both of which have been reported to achieve similar clinical effect in the NCT00833131 trial.. A Markov decision-analytic model compared SCRT plus chemotherapy and LCCRT, by simulating three health states (disease-free survival (DFS), progressive disease (PD) and death). The primary outcomes were quality-adjusted life months (QALMs), costs, and incremental cost-effectiveness ratios (ICERs). Transition probabilities were based on the NCT00833131 trial. The costs were calculated from a Chinese payers' perspective. Strategies were evaluated with a willingness-to-pay (WTP) threshold of $2370.47 (3 × GDP) per QALM gained. Sensitivity analysis was performed to model uncertainty in these parameters.. The overall costs for SCRT plus chemotherapy and LCCRT were $78,937 and $38,140 with effectiveness of 29.92 QALMs and 22.99 QALMs, respectively. SCRT plus chemotherapy increased costs and QALM by $40,797.34 and 6.93 compared to LCCRT, resulting in an ICER of $5884.56/QALM gained. In the DFS state, the whole cost for SCRT plus chemotherapy and LCCRT were $11,490.03 and $10,794.06 with an effectiveness of 21.70 QALMs and 19.65 QALMs, respectively. SCRT plus chemotherapy increased cost and QALM by $695.97 and 2.05 compared to LCCRT, resulting in a ICER of $339.50/QALM gained, which below the WTP. The utility associated with the DFS state was the most influential factor on the cost-effectiveness of SCRT plus chemotherapy. When the cost of PD state below $1920, the ICER of SCRT compared with LCCRT below the WTP.. Compared with LCCRT, SCRT plus chemotherapy is a more cost-effective strategy for locally advanced resectable RC in the DFS state as well as in the all states when the cost of PD state below $1920.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Decision Support Techniques; Fluorouracil; Humans; Leucovorin; Markov Chains; Organoplatinum Compounds; Oxaliplatin; Prognosis; Prospective Studies; Radiotherapy; Rectal Neoplasms; Survival Rate

Recurrence and distant metastases remain a significant issue in locally advanced rectal cancer (LARC). Several multimodal strategies are assessed in clinical trials.. Patients with mid/low magnetic resonance imaging-defined high-risk LARC were randomized to arm A (12-week bevacizumab + FOLFOX-4 then bevacizumab-5-fluorouracil [5-FU]-radiotherapy [RT] before total mesorectal excision [TME]) or arm B (bevacizumab-5-FU-RT then TME). Long-term efficacy and safety up to 5 years' follow-up are reported. No comparison between arms was planned.. Overall, 91 patients (46 in arm A and 45 in arm B) were included. Main results have been presented previously. During the late follow-up period (> 4 weeks after surgery), 4 patients (8.7%) in arm A and 4 (8.9%) in arm B experienced grade 3/4 adverse events related to bevacizumab; the most frequent were 2 anastomotic fistulas (both in arm A) and abscesses (1 in arm A and 2 in arm B). At 5 years' follow-up, 9 (19.6%) and 11 (24.4%) patients in arms A and B developed a fistula in the year after surgery, and 2 (4.3%) in arm A at > 1 year after surgery. Most resolved before study end. Five-year disease-free survival was 70% and 64.3% in arms A and B, respectively. Five-year overall survival was 90.5% (95% confidence interval, 76.7, 96.3) in arm A and 72.7% (95% confidence interval, 56.0, 83.9) in arm B.. Neoadjuvant bevacizumab + FOLFOX-4 may have the potential to increase survival outcomes when followed by bevacizumab-5-FU-RT and TME in LARC. Bevacizumab-5-FU-RT then TME was associated with a higher-than-projected rate of anastomotic fistulas. Further research of neoadjuvant strategies in LARC is encouraged.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Capecitabine; Chemoradiotherapy, Adjuvant; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Lymphatic Metastasis; Magnetic Resonance Imaging; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Oxaliplatin; Rectal Neoplasms; Survival Rate; Young Adult

Although neoadjuvant chemo-radiotherapy (CRT) achieves low local recurrence rates in locally advanced rectal cancer (LARC), it raises a lot of concerns about long-term anal and sexual functions. We explored the efficacy of preoperative chemotherapy with mFOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, and irinotecan) in patients with LARC.. Patients with LARC evaluated by pelvic magnetic resonance imaging (MRI) were enrolled in this trial. All received 4 to 6 cycles of mFOLFOXIRI. MRI was performed to assess clinical response after chemotherapy. Patients with mesorectal fascia-positive or ycT4a/b after re-evaluation would receive radiation before surgery, whereas responders would have immediate total mesorectal excision (TME). Adjuvant chemotherapy with mFOLFOX6 (folinic acid, 5-fluorouracil, and oxaliplatin) was recommended. The primary endpoint was the proportion of tumor downstaging to ypT. Overall, 106 patients were enrolled and received neoadjuvant mFOLFOXIRI chemotherapy. A total of 103 participants underwent TME surgery. Among 103 patients who completed at least 4 cycles of preoperative chemotherapy, 2 received short-term radiation before TME, and 12 underwent long-term CRT after MRI evaluation. The pCR rate was 20.4%, and the tumor downstaging rate was 42.7%. Among patients without preoperative long-term radiotherapy, the pCR rate and tumor downstaging rate were 17.4% and 41.3%, respectively. Among the per-protocol population, the tumor downstaging rate was 48.1%, and the pCR rate was 20.3%. The chemotherapy-related toxicity was well-tolerated.. Neoadjuvant chemotherapy with mFOLFOXIRI and selective radiation does not seem to compromise outcomes in LARC. It could be a reasonable alternative to CRT in previously untreated patients with LARC.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Female; Fluorouracil; Follow-Up Studies; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Oxaliplatin; Preoperative Care; Prognosis; Prospective Studies; Rectal Neoplasms; Survival Rate; Young Adult

BACKGROUND The currently available chemotherapeutic regimens do not use a specifically designed drug delivery system. The objective of this study was to compare outcome measures, adverse effects, and cost of FOLFOX4 and FOLFIRINOX treatments in rectal cancer patients. MATERIAL AND METHODS We enrolled patients who, after surgery, did not undergo chemotherapy or radiotherapy (Control group); were administered 200 mg/m² folinic acid, 400 mg/m² fluorouracil, and 85 mg/m² oxaliplatin (FFO group); or were administered 400 mg/m² folinic acid, 400 mg/m² fluorouracil, 180 mg/m² irinotecan, and 85 mg/m2 oxaliplatin (FFIO group). We recorded tumor and nodal staging, carbohydrate antigen 19-9, serum carcinoembryonic antigen, total cost of treatment, disease recurrence, overall survival, and adverse effects. We used the 2-tailed paired t test following Turkey post hoc test for adverse effects, recurrence analysis, and cost of treatment at 95% of confidence level. RESULTS Surgery (p=0.00089), FOLFOX4 (p=0.000167), and FOLFIRINOX (p=0.00013) improved disease-free conditions. Only surgery failed to maintain carbohydrate antigen and carcinoembryonic antigen 19-9 levels. The cost of chemotherapeutic treatments was in the order of FFIO group > FFO group > Control group. Non-fatal treatment-emergent adverse effects were due to chemotherapeutic drugs. However, fatal chemotherapeutic treatment-emergent adverse effects were observed only in the FFIO group. Overall survival, irrespective of cancerous condition, was higher in the FFO group. CONCLUSIONS FOLFIRINOX had less total cancer recurrence than FOLFOX4. However, FOLFIRINOX had more fatal treatment-emergent adverse effects and excessive cost of treatment than FOLFOX4 regimen.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; China; Disease-Free Survival; Drug Combinations; Drug Costs; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Organometallic Compounds; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms; Treatment Outcome

It is uncertain whether local control is acceptable after preoperative radiotherapy and local excision (LE). An optimal preoperative dose/fractionation schedule has not yet been established.. In a phase III study, patients with cT1-2N0M0 or borderline cT2/T3N0M0 < 4 cm rectal adenocarcinomas were randomised to receive either 5 × 5 Gy plus 1 × 4 Gy boost or chemoradiation: 50.4 Gy in 28 fractions plus 3 × 1.8 Gy boost and 5-fluorouracil with leucovorin bolus. LE was performed 6-8 weeks later. Patients with ypT0-1R0 disease were observed. Completion total mesorectal excision (CTME) was recommended for poor responders, i.e. ypT1R1/ypT2-3.. Of 61 randomised patients, 10 were excluded leaving 51 for analysis; 29 in the short-course group and 22 in the chemoradiation group. YpT0-1R0 was observed in 66% of patients in the short-course group and in 86% in the chemoradiation group, p = 0.11. CTME was performed only in 46% of patients with ypT1R1/ypT2-3. The median follow-up was 8.7 years. Local recurrence incidences and overall survival at 10 years were respectively for the short-course group vs. the chemoradiation group 35% vs. 5%, p = 0.036 and 47% vs. 86%, p = 0.009. In total, local recurrence at 10 years was 79% for ypT1R1/T2-3 without CTME.. This trial suggests that in the LE setting, both local recurrence and survival are worse after short-course radiotherapy than after chemoradiation. Because of the risk of bias, a confirmatory study is desirable. Lack of CTME is associated with an unacceptably high local recurrence rate.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Combined Modality Therapy; Dose Fractionation, Radiation; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Preoperative Care; Rectal Neoplasms; Treatment Outcome

A platinum salt (oxaliplatin or cisplatin) is widely used to enhance chemoradation (CRT) response. The potential of cisplatin in neoadjuvant CRT for locally advanced rectal cancer (LARC) has not been fully investigated. Consecutive patients with histologically confirmed LARC were treated with standard pelvic radiotherapy and concurrent cisplatin plus capecitabine (CisCape CRT). Surgery and eight cycles of adjuvant FOLFOX4 were offered to all patients after CRT. Common biochemical variables and key germline genetic polymorphisms were analyzed as predictors of pathological complete response (pCR). Fifty-one patients were enrolled. pCR (regression AJCC grade 0) was documented in 7 patients (14%), nearly complete response (AJCC grade 1) in 10 pts. There was a strong association between disease-free survival and AJCC grade (p 0.0047). Grade 3-4 toxicities (mainly diarrhea) was observed in 41% of patients. Among all analyzed variables, baseline hemoglobin (Hb) was significantly associated with AJCC grade 0-1 response (p 0.027). As for the pharmacogenetic analysis, XRCC1 rs25487 polymorphism was significantly associated with AJCC grade 0-1, Odds Ratio 25.8, p 0.049. AJCC grade 0-1 response rate for patients with high Hb and/or XRCC1 rs25487 G/G genotype was as high as 57%. Baseline Hb and XRCC1 polymorphisms are valuable selection criteria for the CisCape CRT regimen, given its otherwise meaningful toxicity.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemoradiotherapy, Adjuvant; Cisplatin; Female; Fluorouracil; Hemoglobins; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Polymorphism, Genetic; Predictive Value of Tests; Rectal Neoplasms; X-ray Repair Cross Complementing Protein 1

The randomized "Nordic" LARC study compared preoperative long-course radiotherapy alone (RT) or with chemotherapy (CRT) in the most locally advanced/ugly rectal cancers. Despite significantly better local control in the CRT group, no overall survival benefit was seen after 10 years follow-up. The relations between local control and survival are discussed.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Preoperative Care; Radiotherapy; Rectal Neoplasms

The aim was to evaluate the outcome of treatment-naive patients with synchronous metastatic rectal cancer after chemotherapy with FOLFOXIRI followed by local therapeutic procedures of all tumor lesions as complete as possible.. We reviewed data of 30 patients with synchronous distant metastatic rectal cancer who underwent chemotherapy with FOLFOXIRI and subsequent local therapy in our institution.. Median follow-up was 28 months (range: 8; 74). Cumulative overall survival (OS) and progression-free survival (PFS) was 93.3, 76.9, 55.6% and 46.2, 29.7, 29.7% after 1, 2, 4 years. Non-response to chemotherapy with FOLFOXIRI was associated with a highly significant decreased OS (p < 0.0001). The consistent use of local ablative procedures led to a statistically significant increase in OS (p < 0.0001), but not in PFS (p = 0.635). Patients with ≤ 4 distant metastases showed a better OS (p = 0.033).. Response to intensified first-line chemotherapy with FOLFOXIRI, treatment of the primary rectal tumor, and repeated thorough local ablative procedures in patients with synchronous metastasized rectal cancer may lead to long-term survival, even in a subset of patients with unresectable disease at initial diagnosis.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Progression-Free Survival; Rectal Neoplasms; Survival Analysis; Treatment Outcome

Adding modified FOLFOX6 (folinic acid, fluorouracil, and oxaliplatin) after chemoradiotherapy and lengthening the chemoradiotherapy-to-surgery interval is associated with an increase in the proportion of rectal cancer patients with a pathological complete response.. The purpose of this study was to analyze disease-free and overall survival.. This was a nonrandomized phase II trial.. The study was conducted at multiple institutions.. Four sequential study groups with stage II or III rectal cancer were included.. All of the patients received 50 Gy of radiation with concurrent continuous infusion of fluorouracil for 5 weeks. Patients in each group received 0, 2, 4, or 6 cycles of modified FOLFOX6 after chemoradiation and before total mesorectal excision. Patients were recommended to receive adjuvant chemotherapy after surgery to complete a total of 8 cycles of modified FOLFOX6.. The trial was powered to detect differences in pathological complete response, which was reported previously. Disease-free and overall survival are the main outcomes for the current study.. Of 259 patients, 211 had a complete follow-up. Median follow-up was 59 months (range, 9-125 mo). The mean number of total chemotherapy cycles differed among the 4 groups (p = 0.002), because one third of patients in the group assigned to no preoperative FOLFOX did not receive any adjuvant chemotherapy. Disease-free survival was significantly associated with study group, ypTNM stage, and pathological complete response (p = 0.004, <0.001, and 0.001). A secondary analysis including only patients who received ≥1 cycle of FOLFOX still showed differences in survival between study groups (p = 0.03).. The trial was not randomized and was not powered to show differences in survival. Survival data were not available for 19% of the patients.. Adding modified FOLFOX6 after chemoradiotherapy and before total mesorectal excision increases compliance with systemic chemotherapy and disease-free survival in patients with locally advanced rectal cancer. Neoadjuvant consolidation chemotherapy may have benefits beyond increasing pathological complete response rates. See Video Abstract at http://links.lww.com/DCR/A739.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Chemotherapy, Adjuvant; Disease-Free Survival; Female; Fluorouracil; Follow-Up Studies; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Non-Randomized Controlled Trials as Topic; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms; Rectum; Treatment Outcome

The optimal therapeutic strategy in patients with rectal cancer and synchronous unresectable metastases remains unknown. We evaluated the efficacy of FOLFIRINOX induction therapy in this setting.. Chemotherapy-naïve patients received at least 8 cycles of FOLFIRINOX. The primary end-point was the 4-month disease control (4 m DC) rate. Tumour responses were centrally reviewed and assessed by computed tomography scan for metastases (Response Evaluation Criteria in Solid Tumours criteria) and magnetic resonance imaging for rectal tumorus. With a Simon 2-stage design and a targeted (H1) 4 m DC > 75%, 65 patients were enrolled from July 2012 to February 2015: male, 78%; median age, 61 years; performance status, 0-1, 98%; liver metastases, 92%; ≥2 metastatic sites, 63%.. Fifty-six (85%) of the 65 patients received the 8 planned FOLFIRINOX cycles. The primary objective was achieved (4 m DC rate: 94%; 95% confidence interval [CI], 86.3-97.8). Primary tumour symptoms decreased from 72% at baseline to 10% at 4 months. Response rate was 86%, and a >70% primary tumour volume decrease was seen in 63% of patients. Forty-four patients (68%) had at least one grade 3 side-effect; no toxic deaths occurred. Median follow-up was 35.0 months (95% CI, 31.3-43.7). Median progression-free survival and overall survival were 10.9 m (95% CI, 8.8-12.9) and 33.4 m (95% CI, 22.6-38.2), respectively.. Upfront FOLFIRINOX is feasible and allows good local and distant control. It therefore offers the opportunity to choose the best therapeutic strategy for each patient and to personalise treatment according to the local and distant efficacy results of this induction step.. Clinicaltrials.gov, NCT01674309.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Fatigue; Female; Fluorouracil; Follow-Up Studies; Gastrointestinal Diseases; Hematologic Diseases; Humans; Irinotecan; Kaplan-Meier Estimate; Leucovorin; Liver Neoplasms; Lung Neoplasms; Magnetic Resonance Imaging; Male; Middle Aged; Oxaliplatin; Paresthesia; Progression-Free Survival; Rectal Neoplasms; Remission Induction; Tomography, X-Ray Computed; Treatment Outcome

The NORDIC-VII study is a randomised phase III trial of cetuximab plus continuous or intermittent fluorouracil, folinic acid, and oxaliplatin (Nordic FLOX) vs FLOX alone in first-line treatment of metastatic colorectal cancer. The present report presents an updated and final survival analysis with BRAF and extended RAS mutational status, 5 years after the primary analysis.. A total of 566 patients were included in the intention-to-treat (ITT) population of the NORDIC-VII study. Updated survival status was obtained from 176 patients who were alive in the primary survival analyses. Samples from 223 tumours previously found to be KRAS (exon 2) and BRAF (V600E) wild-type, were re-analysed for KRAS (exons 3 and 4) and NRAS (exons 2-4) mutations.. Including the extended RAS analyses, RAS and BRAF mutational status was available from 457 patients (81% of the ITT population). RAS was mutated in 46% and BRAF in 12% of the tumours. RAS and BRAF, if mutated, were negative prognostic factors. The updated analyses confirmed the finding of the primary report that cetuximab did not provide any additional benefit when added to FLOX in patients with RAS/BRAF wild-type tumours, neither on progression-free nor overall survival. However, the outcomes in a subset of patients, which, after the first eight treatment cycles, received cetuximab alone, suggested a beneficial effect of cetuximab monotherapy.. Adding cetuximab to Nordic FLOX did not provide any clinical benefit, but the data suggested an effect of cetuximab monotherapy in patients with RAS/BRAF wild-type tumours in the NORDIC-VII cohort. The data were compatible with a negative interaction between cetuximab and the Nordic FLOX chemotherapy backbone.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cetuximab; Colonic Neoplasms; Disease-Free Survival; DNA Mutational Analysis; Female; Fluorouracil; GTP Phosphohydrolases; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Membrane Proteins; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Proportional Hazards Models; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras); Rectal Neoplasms; Survival Rate; Young Adult

The potential of chemotherapy as salvage treatment after failure of neoadjuvant chemoradiotherapy for locally advanced rectal cancer (LARC) has never been explored. We conducted a single-center, retrospective analysis to address this question.. Patients with newly diagnosed LARC who were inoperable or candidates for extensive (i.e., beyond total mesorectal excision [TME]) surgery after long-course chemoradiotherapy and who received salvage chemotherapy were included. The primary objective was to estimate the proportion of patients who became suitable for TME after chemotherapy.. Forty-five patients were eligible (39 candidates for extensive surgery and 6 unresectable). Previous radiotherapy was given concurrently with chemotherapy in 43 cases (median dose: 54.0 Gy). Oxaliplatin- and irinotecan-based salvage chemotherapy was administered in 40 (88.9%) and 5 (11.1%) cases, respectively. Eight patients (17.8%) became suitable for TME after chemotherapy, 10 (22.2%) ultimately underwent TME with clear margins, and 2 (4.4%) were managed with a watch and wait approach. Additionally, 13 patients had extensive surgery with curative intent. Three-year progression-free survival and 5-year overall survival in the entire population were 30.0% (95% confidence interval [CI]: 15.0-46.0) and 44.0% (95% CI: 26.0-61.0), respectively. For the curatively resected and "watch and wait" patients, these figures were 52.0% (95% CI: 27.0-73.0) and 67.0% (95% CI: 40.0-84.0), respectively.. Systemic chemotherapy may be an effective salvage strategy for LARC patients who fail to respond to chemoradiotherapy and are inoperable or candidates for beyond TME surgery. According to our study, one out of five patients may become resectable or be spared from an extensive surgery after systemic chemotherapy.. High-quality evidence to inform the optimal management of rectal cancer patients who are inoperable or candidates for beyond total mesorectal excision surgery following standard chemoradiotherapy is lacking. We show for the first time that systemic chemotherapy may be beneficial and result in one out of five poor prognosis patients becoming resectable or being spared from an extensive surgical approach. Although mores studies are needed to confirm these data, administering salvage systemic chemotherapy in this setting may have the potential to minimize morbidity associated with extensive surgical procedures and improve long-term oncological outcome.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemoradiotherapy; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms; Retrospective Studies; Salvage Therapy

Various types of preoperative chemoradiotherapy (CRT) have been established for rectal cancer; thus, Physicians will need to refine the selection of appropriate preoperative CRT for different patients since there are various treatment regimens. Oral tegafur-uracil (UFT) plus leucovorin (LV) is commonly used to treat rectal cancer in Japan. Oral chemotherapy offers patients many potential advantages. Since 2008, we have been performing preoperative CRT with intermittent oral UFT plus LV in locally advanced rectal cancer patients to prevent postoperative local recurrence. Here, in a retrospective analysis, we evaluated the efficacy and short-term outcomes of preoperative CRT with intermittent oral UFT plus LV.. The completion rate of CRT was high at 94% (n = 29/31). The downstaging rate of CRT was 61% (n = 19/31). The pathological complete response rate was 6.5% (n = 2/31). Significant differences were observed in the 3-year local recurrence rate between the two groups (P < 0.05).. Preoperative CRT with intermittent oral UFT plus LV appears to be a tolerable and effective treatment for Japanese patients with rectal cancer. A further investigation of a diversification of preoperative CRT for Japanese rectal cancer patients is required.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Combined Modality Therapy; Female; Follow-Up Studies; Humans; Japan; Leucovorin; Male; Middle Aged; Neoplasm Staging; Preoperative Care; Prognosis; Rectal Neoplasms; Retrospective Studies; Survival Rate; Tegafur

This prospective multicenter phase 2 study aimed to evaluate the feasibility and efficacy of neoadjuvant chemotherapy (NAC) without radiotherapy for locally advanced rectal cancer (LARC).. Patients with LARC (cStage II and III) were included in the study. Those with cT4b tumor were excluded. Six cycles of modified FOLFOX6 (mFOLFOX6) plus either bevacizumab or cetuximab, depending on KRAS status, were administered before surgery. The primary end point of the study was the R0 resection rate. The secondary end points were adverse effect, rate of NAC completion, postoperative complications, and pathologic complete response (pCR) rate.. The study enrolled 60 patients from eight institutions. For the study, mFOLFOX6 was administered with cetuximab to 40 patients who had wild-type KRAS and with bevacizumab to 20 patients who had KRAS mutations. The completion rate for NAC was 88.4%. Sphincter-preserving surgery was performed for 43 patients and abdominoperineal resection for 17 patients. The median operation time was 335 min, and the median blood loss was 40 g. The R0 resection rate was 98.3%, and the pCR rate was 16.7%. The overall postoperative complication rate (≥grade 2) was 21.7%. The complications included anastomotic leakage (11.6%), surgical-site infection (6.7%), and urinary dysfunction (3.3%). The patients with wild-type KRAS did not differ significantly from those with KRAS mutations in terms of response rate, postoperative complication rate, and pCR rate.. The findings show that NAC is a feasible and promising treatment option for LARC (This study is registered with UMIN-CTR, UMIN000005654).

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cetuximab; Feasibility Studies; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaliplatin; Prognosis; Prospective Studies; Rectal Neoplasms; Survival Rate

At present, there are common recommendations for treatment for stage II-III resectable rectal cancer patients: preoperative conventional chemoradiotherapy (CRT) with delayed surgery in 6-8 weeks or preoperative short-course radiotherapy (SCRT) followed by immediate surgery. The aim of this study was to compare overall survival (OS) and disease-free survival (DFS) in two treatment groups: preoperative SCRT and CRT both with delayed surgery plus adjuvant chemotherapy in CRT arm.. A total of 150 patients were randomly assigned to two groups: 75 to CRT (preoperative conventional CRT, 50Gy/25 fr with fluorouracil and leucovorin on the 1st and the 5th week of RT followed by TME surgery in 6-8 weeks and 4 cycles of adjuvant fluorouracil/leucovorin every 4 weeks; then follow-up) and 75 to SCRT (preoperative short-course RT, 25Gy/5 fr followed by TME surgery in 6-8 weeks; then follow-up). The data of 140 patients (72 in CRT and 68 in SCRT group) were included in statistical analysis. Primary end points were OS and DFS.. Median follow-up was 60.5 (range, 5-108) months. The 5-year DFS was 67% in the CRT group (n=72) and 45% in the SCRT group (n=68) (P=0.013; HR=1.88; 95% CI, 1.13-3.12; P=0.015). The 5-year OS was 79% and 62% in the CRT and SCRT groups, respectively (P=0.015; HR=2.05; 95% CI, 1.13-3.70; P=0.017). The 5-year OS for intent-to-treat (ITT) population (n=150) was 78% in the CRT and 58% in the SCRT group (P=0.003; HR=2.28; 95% CI, 1.30-4.00; P=0.004).. The 5-year DFS and OS were significantly better in the CRT than the SCRT group. For ITT population, OS was also significantly better after CRT versus SCRT.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Chemotherapy, Adjuvant; Combined Modality Therapy; Disease-Free Survival; Fluorouracil; Humans; Leucovorin; Rectal Neoplasms

To compare treatment and toxicity outcomes between a phase 2 institutional trial of near total neoadjuvant therapy (nTNT) for locally advanced rectal cancer and a similar historical control cohort treated at Washington University in St. Louis with the current US standard of care, defined as neoadjuvant chemoradiotherapy (NCRT), total mesorectal excision (TME), and adjuvant FOLFOX chemotherapy; to expand the comparison to an additional institution, patients treated with similar NCRT at Stanford University were included.. Sixty-nine patients with cT3-4N0-2M0 rectal adenocarcinoma enrolled on the Washington University in St. Louis phase 2 study of nTNT were included for analysis. Patients treated at the same institution with conventional NCRT and adjuvant FOLFOX were matched for exact cTNM stage. Forty-one patients treated with NCRT at Stanford University were included in a second analysis. Kaplan-Meier analysis with log-rank test was used to compare local control, distant metastasis-free survival, disease-free survival, and overall survival.. Median follow-up was 49 and 54 months for nTNT and NCRT, respectively. Pathologic complete response and T-downstaging rates were 28% versus 16% (P=.21) and 75% versus 41% (P<.001) in the nTNT and NCRT cohorts, respectively. Three-year disease-free survival (85% vs 68%, P=.032) was significantly better in the nTNT group. Actuarial 3-year local control (92% vs 96%, P=.36) and overall survival (96% vs 88%, P=.67) were similar. The Stanford cohort had significantly lower clinical stage. After controlling for clinical stage, age, tumor location, institution, and number of chemotherapy cycles, nTNT treatment remained significantly associated with lower risk of recurrence (P=.006).. Patients treated with nTNT had higher T-downstaging and superior distant metastasis-free survival and disease-free survival compared with conventional NCRT when matched for tumor location and exact cTNM stage. Near total neoadjuvant therapy remained a significant multivariate predictor for improved outcome when including patients treated with NCRT at another institution.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Disease-Free Survival; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Matched-Pair Analysis; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Organoplatinum Compounds; Preoperative Care; Radiotherapy; Rectal Neoplasms

A randomized phase II/III trial was started in May 2015 comparing perioperative versus postoperative chemotherapy with modified infusional fluorouracil and folinic acid with oxaliplatin for lower rectal cancer patients with suspected lateral pelvic node metastasis. The standard arm is total mesorectal excision or tumor-specific mesorectal excision with lateral pelvic node dissection (LND) followed by postoperative chemotherapy (modified infusional fluorouracil and folinic acid with oxaliplatin; 12 cycles). The experimental (perioperative chemotherapy) arm is six courses of modified infusional fluorouracil and folinic acid with oxaliplatin before and six courses after total mesorectal excision with lateral pelvic node dissection. The aim of this trial is to confirm the superiority of perioperative chemotherapy. A total of 330 patients will be enrolled over 7 years. The primary endpoint in Phase II part is proportion of R0 resection and that in Phase III part is overall survival. Secondary endpoints are progression-free survival, local progression-free survival, etc. This trial has been registered in the UMIN Clinical Trials Registry as UMIN000017603 [http://www.umin.ac.jp/ctr/index-j.htm].

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Drug Administration Schedule; Female; Fluorouracil; Humans; Injections, Intravenous; Japan; Leucovorin; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Postoperative Period; Preoperative Period; Rectal Neoplasms

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; China; Combined Modality Therapy; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Prevalence; Radiation Injuries; Rectal Neoplasms; Risk Factors; Treatment Outcome

During an ongoing phase II observational study on watch and wait policy in rectal cancer, a substantial number of patients presented residual lesion after radiotherapy with a clinical benign appearance. This article aims to discuss the clinical significance of such findings.. Main entry criteria were age ≥70 years and small tumour (≤5 cm and ≤60% of circumferential involvement) located in the low rectum. Patients received chemoradiation (50 Gy, 2 Gy per fraction concomitantly with a 5-Fu bolus and leucovorin) or 5 × 5 Gy if considered unfit for chemotherapy. Patients with clinical complete response (cCR) were observed. Those with persistent tumours underwent transanal endoscopic microsurgery [TEM] if the baseline tumour was ≤3 cm and cN0 or total mesorectal excision.. The watch and wait procedure was used in 11 out of the total 35 patients (31%) with a cCR; 17 patients (49%) with residual tumours that appeared clinically malignant were referred for TEM or abdominal surgery. In the remaining seven (20%), the residual tumour clinically appeared benign. Of these, there were two invasive cancers, four high-grade dysplasias and one low-grade dysplasia. The five patients with dysplasia, underwent local lesion resection without recurrence within a median of 11 months follow-up.. The majority of lesions that appeared clinically benign after radio(chemo)therapy were also benign on pathological examination. Thus, local excision of such lesions should be considered.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Dose Fractionation, Radiation; Female; Fluorouracil; Humans; Leucovorin; Male; Neoplasm, Residual; Organ Sparing Treatments; Rectal Neoplasms; Transanal Endoscopic Microsurgery; Tumor Burden; Watchful Waiting

To evaluate the efficacy and safety of upfront mFOLFOX6 followed by short-course radiotherapy (SCRT) and surgery in patients with locally advanced rectal cancer and liver-only metastases.. This single-arm phase II study involved 32 patients. mFOLFOX6 was administered for four cycles followed by SCRT and another four cycles of mFOLFOX6. Surgery was performed 4-6 weeks after the last chemotherapy cycle. The primary endpoint was complete (R0) resection rate. Secondary endpoints were response rate, progression-free survival (PFS), overall survival (OS), and complication rates.. Surgical resection of the rectum and liver was performed in 25 patients (78%) and R0 resection was achieved in 20 patients (63%). Local tumor downstaging was observed in 54% of patients. Median OS and PFS were 38 and 9 months, respectively. One patient discontinued treatment due to toxicity and no treatment-related deaths occurred. Patients who progressed after 4 cycles of mFOLFOX6 were less likely to receive resection.. This regimen was safe and effective in inducing local tumor response and achieving R0 resection in this patient population.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Disease-Free Survival; Dose Fractionation, Radiation; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Grading; Neoplasm Staging; Organoplatinum Compounds; Rectal Neoplasms; Survival Analysis; Treatment Outcome

This non-randomised study was undertaken to examine oxaliplatin as possibly an intensifying component of sequential neoadjuvant therapy in locally advanced rectal cancer for improved local and metastatic outcome.. Ninety-seven patients (57 T2-3 cases, 40 T4 cases) received two cycles of the Nordic FLOX regimen (oxaliplatin 85 mg/m(2) day 1 and bolus 5-fluorouracil 500 mg/m(2) and folinic acid 100 mg days 1 and 2) before long-course chemoradiotherapy with concomitant oxaliplatin and capecitabine, followed by pelvic surgery. Treatment toxicity, local tumour response and long-term outcome were recorded.. Good histologic tumour regression was obtained in 72% of patients. Implementing protocol-specific dose adjustments, tolerance was acceptable and 95% of patients received the total prescribed radiation dose. Estimated 5 year progression-free and overall survival were 61% and 83%, respectively. T4 stage was associated with an inferior local response rate, which again was highly associated with impaired long-term outcome.. In this cohort of rectal cancer patients dominated by T4 and advanced T3 cases given sequential oxaliplatin-containing preoperative therapy with acceptable toxicity, high tumour response rates and overall survival were obtained, consistent with both local and systemic effects. However, tumour response and long-term outcome remained inferior for a significant number of T4 cases, suggesting that the T4 entity is biologically heterogeneous with subgroups of patients eligible for further individualisation of therapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemoradiotherapy; Disease Progression; Disease-Free Survival; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms; Treatment Outcome

A prospective phase 2 trial of short-course (SC) radiation therapy (RT) with 25 Gy over 5 fractions, followed by 4 cycles of 5-fluorouracil, oxaliplatin, and leucovorin (mFOLFOX6) before surgery was recently completed at our institution. We present here the patient-reported quality of life (QOL) outcomes from this trial.. Eighty patients with cT3/T4, any N, any M rectal adenocarcinoma planned for resection were enrolled between 2009 and 2012. The QOL data were obtained prospectively using the Functional Assessment of Cancer Therapy-Colon (FACT-C) questionnaire before RT, before surgery, and 1 year after surgery. The previously validated minimally importance difference (MID) method was used to measure clinically significant QOL changes in FACT-C scores for each patient across time points. We examined the role of ostomy on QOL. We also compared QOL with disease outcomes and physician-reported toxicity.. The FACT-C questionnaire was completed by 97% of patients before RT, 85% immediately before surgery, and 62% 1 year after surgery. There was no statistically significant change in mean FACT-C scores from before treatment to after treatment. The majority of patients had either no change or an increase in QOL 1 year after treatment using the MID method. There were significant changes in QOL between patients with ostomy versus no ostomy 1 year after treatment for functional well-being (FWB) (14.81 vs 20.52, P=.018) and the colorectal cancer subscale (CCS) using the MID method (P=.004). Patients without ostomy reported stable changes in bowel control 1 year after surgery. There was no statistically significant correlation between QOL and disease recurrence, pathologic complete response, pathologic T stage downstaging, or acute/late toxicity.. SC-RT and sequential mFOLFOX6 as preoperative therapy for rectal cancer results in stable patient-reported QOL outcomes 1 year after treatment. These findings in conjunction with previously reported oncologic outcomes support further evaluation of this regimen in a phase 3 setting.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Combined Modality Therapy; Dose Fractionation, Radiation; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Patient Satisfaction; Preoperative Care; Quality of Life; Radiotherapy Dosage; Rectal Neoplasms; Treatment Outcome

Total mesorectal excision with fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy is a standard treatment of locally advanced rectal cancer. This study investigated the addition of oxaliplatin with and without preoperative radiotherapy.. In this multicenter, open-label, phase III trial, we randomly assigned (1:1:1) Chinese adults (age 18 to 75 years) with locally advanced stage II/III rectal cancer to three treatments: five 2-week cycles of infusional fluorouracil (leucovorin 400 mg/m(2), fluorouracil 400 mg/m(2), and fluorouracil 2.4 g/m(2) over 48 h) plus radiotherapy (46.0 to 50.4 Gy delivered in 23 to 25 fractions during cycles 2 through 4) followed by surgery and seven cycles of infusional fluorouracil, the same treatment plus intravenous oxaliplatin 85 mg/m(2) on day 1 of each cycle (modified FOLFOX6 [mFOLFOX6]), or four to six cycles of mFOLFOX6 followed by surgery and six to eight cycles of mFOLFOX6. Random assignment was performed by using computer-generated block randomization codes. The primary end point was 3-year disease-free survival. Secondary end points of histopathologic response and toxicity are reported.. A total of 495 patients were enrolled from June 2010 to February 2015; 475 were evaluable (fluorouracil-radiotherapy, n = 155; mFOLFOX6-radiotherapy, n = 157; mFOLFOX6, n = 163). In the fluorouracil-radiotherapy, mFOLFOX6-radiotherapy, and mFOLFOX6 groups, the rate of pathologic complete response (pCR) was 14.0%, 27.5%, and 6.6%, and downstaging (ypStage 0 to 1) was achieved by 37.1%, 56.4%, and 35.5% of patients, respectively. Higher toxicity and more postoperative complications were observed in patients who received radiotherapy.. mFOLFOX6-based preoperative chemoradiotherapy results in a higher pCR rate than fluorouracil-based treatment. Perioperative mFOLFOX6 alone had inferior results and a lower pCR rate than chemoradiotherapy but led to a similar downstaging rate as fluorouracil-radiotherapy, with less toxicity and fewer postoperative complications.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Chemotherapy, Adjuvant; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Rectal Neoplasms

Whether there is any benefit derived from adding oxaliplatin to fluoropyrimidine-based preoperative chemoradiation is currently unknown in cases of advanced cT3 or cT4 tumours. Our aim was to evaluate this issue by analysing a randomized trial, which compared two schedules of preoperative treatment (chemoradiation vs. 5 × 5 Gy with 3 cycles of consolidation chemotherapy) for cT4 or fixed cT3 rectal cancer.. Delivery of oxaliplatin was mandatory to the first part of the study. For the second part, its delivery in both treatment-assigned groups was left to the discretion of the local investigator. We analysed a subgroup of 272 patients (136 in the oxaliplatin group and 136 in the fluorouracil-only group) from institutions that had omitted oxaliplatin in the second part of the study.. No benefit was found of adding oxaliplatin in terms of CRM nor pCR rates for either concomitant or sequential settings in preoperative radiochemotherapy for very advanced rectal cancer.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Digestive System Surgical Procedures; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Prospective Studies; Rectal Neoplasms; Treatment Outcome

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Female; Fluorouracil; Guidelines as Topic; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Organoplatinum Compounds; Poland; Prevalence; Radiation Injuries; Radiotherapy, Adjuvant; Rectal Neoplasms; Risk Assessment; Survival Rate; Treatment Outcome

To report secondary efficacy endpoints of Radiation Therapy Oncology Group protocol 0247, primary endpoint analysis of which demonstrated that preoperative radiation therapy (RT) with capecitabine plus oxaliplatin achieved a pathologic complete remission prespecified threshold (21%) to merit further study, whereas RT with capecitabine plus irinotecan did not (10%).. A randomized, phase 2 trial evaluated preoperative RT (50.4 Gy in 1.8-Gy fractions) with 2 concurrent chemotherapy regimens: (1) capecitabine (1200 mg/m(2)/d Monday-Friday) plus irinotecan (50 mg/m(2)/wk × 4); and (2) capecitabine (1650 mg/m(2)/d Monday-Friday) plus oxaliplatin (50 mg/m(2)/wk × 5) for clinical T3 or T4 rectal cancer. Surgery was performed 4 to 8 weeks after chemoradiation, then 4 to 6 weeks later, adjuvant chemotherapy (oxaliplatin 85 mg/m(2); leucovorin 400 mg/m(2); 5-fluorouracil 400 mg/m(2); 5-fluorouracil 2400 mg/m(2)) every 2 weeks × 9. Disease-free survival (DFS) and overall survival (OS) were estimated univariately by the Kaplan-Meier method. Local-regional failure (LRF), distant failure (DF), and second primary failure (SP) were estimated by the cumulative incidence method. No statistical comparisons were made between arms because each was evaluated individually.. A total of 104 patients (median age, 57 years) were treated; characteristics were similar for both arms. Median follow-up for RT with capecitabine/irinotecan arm was 3.77 years and for RT with capecitabine/oxaliplatin arm was 3.97 years. Four-year DFS, OS, LRF, DF, and SP estimates for capecitabine/irinotecan arm were 68%, 85%, 16%, 24%, and 2%, respectively. The 4-year DFS, OS, LRF, DF, and SP failure estimates for capecitabine/oxaliplatin arm were 62%, 75%, 18%, 30%, and 6%, respectively.. Efficacy results for both arms are similar to other reported studies but suggest that pathologic complete remission is an unsuitable surrogate for traditional survival metrics of clinical outcome. Although it remains uncertain whether the addition of a second cytotoxic agent enhances the effectiveness of fluorouracil plus RT, these results suggest that further study of irinotecan may be warranted.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Capecitabine; Chemoradiotherapy; Deoxycytidine; Drug Administration Schedule; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaliplatin; Radiation-Sensitizing Agents; Radiotherapy Dosage; Rectal Neoplasms; Salvage Therapy; Survival Analysis

The discussion on the role of adjuvant chemotherapy for rectal cancer patients treated according to current guidelines is still ongoing. A multicentre, randomized phase III trial, PROCTOR-SCRIPT, was conducted to compare adjuvant chemotherapy with observation for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision (TME).. The PROCTOR-SCRIPT trial recruited patients from 52 hospitals. Patients with histologically proven stage II or III rectal adenocarcinoma were randomly assigned (1:1) to observation or adjuvant chemotherapy after preoperative (chemo)radiotherapy and TME. Radiotherapy consisted of 5 × 5 Gy. Chemoradiotherapy consisted of 25 × 1.8-2 Gy combined with 5-FU-based chemotherapy. Adjuvant chemotherapy consisted of 5-FU/LV (PROCTOR) or eight courses capecitabine (SCRIPT). Randomization was based on permuted blocks of six, stratified according to centre, residual tumour, time between last irradiation and surgery, and preoperative treatment. The primary end point was overall survival.. Of 470 enrolled patients, 437 were eligible. The trial closed prematurely because of slow patient accrual. Patients were randomly assigned to observation (n = 221) or adjuvant chemotherapy (n = 216). After a median follow-up of 5.0 years, 5-year overall survival was 79.2% in the observation group and 80.4% in the chemotherapy group [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.62-1.39; P = 0.73]. The HR for disease-free survival was 0.80 (95% CI 0.60-1.07; P = 0.13). Five-year cumulative incidence for locoregional recurrences was 7.8% in both groups. Five-year cumulative incidence for distant recurrences was 38.5% and 34.7%, respectively (P = 0.39).. The PROCTOR-SCRIPT trial could not demonstrate a significant benefit of adjuvant chemotherapy with fluoropyrimidine monotherapy after preoperative (chemo)radiotherapy and TME on overall survival, disease-free survival, and recurrence rate. However, this trial did not complete planned accrual.. Dutch Colorectal Cancer group, CKTO 2003-16, ISRCTN36266738.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemotherapy, Adjuvant; Combined Modality Therapy; Digestive System Surgical Procedures; Female; Fluorouracil; Follow-Up Studies; Humans; Incidence; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Netherlands; Prognosis; Radiotherapy, Adjuvant; Rectal Neoplasms; Survival Rate

We investigated the relationships between biomarkers related to endoplasmic reticulum stress proteins (glucose-regulated protein of molecular mass 78 [GRP78] and Cripto-1 [teratocarcinoma-derived growth factor 1 protein]), pathologic response, and prognosis in locally advanced rectal cancer.. All clinical stage II and III rectal cancer patients received 50.4 Gy over 5.5 weeks, plus 5-fluorouracil (400 mg/m(2)/day) and leucovorin (20 mg/m(2)/day) bolus on days 1 to 5 and 29 to 33, and surgery was performed at 7 to 10 weeks after completion of all therapies. Expression of GRP78 and Cripto-1 proteins was determined by immunohistochemistry and was assessed in 101 patients with rectal cancer treated with neoadjuvant chemoradiotherapy (CRT).. High expression of GRP78 and Cripto-1 proteins was observed in 86 patients (85.1%) and 49 patients (48.5%), respectively. Low expression of GRP78 protein was associated with a significantly high rate of down staging (80.0% vs. 52.3%, respectively; p=0.046) and a significantly low rate of recurrence (0% vs. 33.7%, respectively; p=0.008) compared with high expression of GRP78 protein. Mean recurrence-free survival according to GRP78 expression could not be estimated because the low expression group did not develop recurrence events but showed a significant correlation with time to recurrence, based on the log rank method (p=0.007). GRP78 also showed correlation with overall survival, based on the log rank method (p=0.045).. GRP78 expression is a predictive and prognostic factor for down staging, recurrence, and survival in rectal cancer patients treated with 5-fluorouracil and leucovorin neoadjuvant CRT.

Topics: Aged; Biomarkers, Tumor; Chemoradiotherapy, Adjuvant; Endoplasmic Reticulum Chaperone BiP; Female; Fluorouracil; GPI-Linked Proteins; Heat-Shock Proteins; Humans; Intercellular Signaling Peptides and Proteins; Laparoscopy; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Proteins; Prognosis; Rectal Neoplasms

The R98 trial explores the addition of irinotecan to a 5-fluorouracil (5-FU) plus leucovorin (5-FU/LV) adjuvant regimen in optimally resected stages II-III rectal cancers. We report the updated long-term results. Disease-free survival (DFS) was the primary end point.. Between March 1999 and December 2005, 357 patients were randomized: 178 in 5-FU/LV and 179 in LV5-FU2 + irinotecan arm. The trial was stratified by control arm: Mayo Clinic regimen or LV5-FU2 regimen.. Three hundred and fifty-seven randomized patients were evaluable for efficacy. With a follow-up of 156 months, the DFS was in favour of experimental arm but did not reach statistical significance [hazard ratio (HR) = 0.80, P = 0.154]. The same was observed for overall survival (OS) (HR = 0.87, P = 0.433). The 5-year DFS was 58% in the control arm and 63% in the experimental arm. The 5-year OS was 74% in the control arm and 75% in the experimental arm. Patients allocated to the experimental arm had more grade 3-4 neutropenia when compared with the LV5-FU2 arm (33% versus 6%, P = 0.03), but not when compared with the Mayo Clinic arm (33% versus 36%, P = 0.84). Grade 3-4 diarrhoea tended to be higher in the experimental arm, but analyses stratified by control arm or by radiotherapy failed to show significant differences across strata (test for interaction P = 0.44).. Even though a benefit of irinotecan in subgroups of patients cannot be excluded, due to early termination and lack of power, the study does not support the addition of irinotecan to 5-FU/LV in routine in patients with resected stage II-III rectal cancer.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Disease Progression; Disease-Free Survival; Early Termination of Clinical Trials; Female; Fluorouracil; France; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Neoplasm Staging; Rectal Neoplasms; Risk Factors; Survival Analysis; Time Factors; Treatment Outcome

Induction chemotherapy has many benefits of in locally advanced rectal cancer (LARC); one of these is the better control of distant failure. Hyperfractionated radiotherapy (HFRT) is new approach still on evaluation in preoperative setting of rectal cancer. We aimed to evaluate the efficacy of induction FOLFOX followed by HFRT in LARC. From September 2011 to December 2013, 27 patients with LARC were enrolled in this prospective, phase I-II study. Induction FOLFOX bolus was given for two cycles followed by HFRT (1.5 Gy twice day for 30 fractions over 3 weeks for a total of 45 Gy). 5-fluorouracil (5-FU) bolus was administrated during first and last 3 days of radiotherapy. Surgical resection was performed in 4-5 weeks further and followed by adjuvant FOLFOX bolus regimen. Twenty-one (77.8 %) patients were males and 22. 2 % of patients were females, and the median age at diagnosis was 46 years. Low sited tumor was the most presenting site (55.6 %). Clinically positive lymph nodes were presented in 70.4 % of patients. Twenty patients (74.1 %) underwent sphincter sparing procedure. Pathological complete response (pCR) was achieved in seven patients (25.9 %). Tumor and nodal downstaging were recorded in (70.3 %) and (42.1 %) of patients, respectively. Acute and late toxicities were in acceptable range. Two-year disease-free survival was 70.2 %, and overall survival was 87.5 %. Induction FOLFOX followed by HFRT and concurrent 5-FU improves pCR in LARC, and this combination was feasible with acceptable toxicity. Further evaluations are mandatory for this new approach.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Dose Fractionation, Radiation; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Preoperative Care; Prognosis; Prospective Studies; Rectal Neoplasms; Survival Rate

The 5-year oncologic outcomes from the trial regimen were excellent. However, the neoadjuvant and surgical toxicity of this regimen was significant and was the primary reason for the low compliance with adjuvant systemic therapy.Due to the lack of an improvement in the pathologic complete response rate, the substantial associated toxicity, and the negative phase III trials of adjuvant bevacizumab in colon cancer, this regimen will not be pursued for further study.. The addition of bevacizumab to chemotherapy improves overall survival for metastatic colorectal cancer. We initiated a phase II trial to evaluate preoperative capecitabine, oxaliplatin, and bevacizumab with radiation therapy (RT) followed by surgery and postoperative 5-fluorouracil, leucovorin, oxaliplatin (FOLFOX), and bevacizumab for locally advanced rectal cancer. The purpose of this report is to describe the 5-year oncologic outcomes of this regimen.. In a phase II Simon two-stage design study, we evaluated preoperative treatment with capecitabine (825 mg/m(2) b.i.d. Monday-Friday), oxaliplatin (50 mg/m(2) weekly), bevacizumab (5 mg/kg on days 1, 15, and 29), and RT (50.4 Gy). Surgery was performed by 8 weeks after RT. Beginning 8-12 weeks after surgery, patients received FOLFOX plus bevacizumab (5 mg/kg) every 2 weeks for 12 cycles (oxaliplatin stopped after 9 cycles). The primary endpoint was a pathologic complete response (path-CR) rate of 30%. Fifty-seven patients with resectable T3/T4 rectal adenocarcinoma were enrolled between 2006 and 2010.. Of 57 enrolled patients, 53 were eligible and included in the analysis. Forty-eight (91%) patients completed preoperative therapy, all of whom underwent curative surgical resection. Nine patients (17%) achieved path-CR. There were 29 worst grade 3 events, 8 worst grade 4 events, and 2 patient deaths, 1 of which was attributed to study therapy. Twenty-six patients (54%) began adjuvant chemotherapy. After a median follow-up period of 41 months, the 5-year overall survival (OS) rate for all patients was 80%. Only 2 patients experienced cancer recurrence: 1 distant (liver) and 1 loco-regional (pelvic lymph nodes), respectively. Both of these patients are still alive. The 5-year relapse-free survival rate was 81%.. Despite the path-CR primary endpoint of this trial not being reached, the 5-year OS and recurrence-free survival rates were excellent. However, the neoadjuvant and surgical toxicity of this regimen was significant and was the primary reason for the low compliance with adjuvant systemic therapy. Because of the lack of an improvement in the path-CR rate, the substantial associated toxicity, and the negative phase III trials of adjuvant bevacizumab in colon cancer, this regimen will not be pursued for further study.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Capecitabine; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms

Current neoadjuvant chemoradiotherapy had limited impact on distal metastasis and survival in locally advanced rectal cancer. Here, we investigated a new sandwich-like neoadjuvant regimen with bevacizumab.. This was a single-arm, open-labeled, phase II trial. Patients with locally advanced rectal cancer received sandwich-like neoadjuvant therapy with bevacizumab (induction therapy with bevacizumab and FOLFOX, concurrent chemoradiotherapy with bevacizumab and consolidation chemotherapy with FOLFOX). Surgery was performed 4-6 weeks later. The primary endpoint of this study was pathologic complete response.. Twenty-five eligible patients were included. All completed the neoadjuvant therapy protocol. During the course of neoadjuvant therapy, 3 patients (12 %) had grade 4 hematological toxicity events and 12 (48 %) had grade 3 non-hematological toxicity events. According to RECIST criteria, 18 patients (72 %) achieved partial response and the rest seven patients (28 %) remained stable disease. Two patients (8 %) refused the subsequent surgical therapy for personal reasons, and 23 patients (92 %) underwent operations finally. Nine (39.1 %, 95 % CI 18.0-57.5 %) of them achieved pathologic complete response. Five of them (21.7 %) had postoperative complications. After a median follow-up period of 25.3 (14.4-40.9) months, four patients developed disease progression and two died of cancer. The 3-year overall survival rate was 95 % (95 % CI 69.5-99.3 %), and the 3-year disease-free survival rate was 72.5 % (95 % CI 33.7-90.9 %).. Sandwich-like neoadjuvant therapy with bevacizumab is safe and effective for locally advanced rectal cancer.

Topics: Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Chemoradiotherapy; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Rectal Neoplasms; Young Adult

Neoadjuvant chemoradiotherapy (CRT) followed by total mesorectal excision is considered the standard of care for patients with locally advanced adenocarcinoma of the middle/low rectum. The present study evaluated the feasibility of using modified FOLFOX6 regimen as an adjuvant treatment for high-risk patients with locally advanced rectal cancer (LARC) treated with neoadjuvant CRT.. Forty patients with LARC (ypT3-4 or N+) treated with neoadjuvant CRT were enrolled at Kyungpook National University Medical Center (Daegu, Korea) between December 2011 and December 2012. All the patients underwent rectal surgery with curative intent 8 weeks after the end of the neoadjuvant treatment. Adjuvant chemotherapy using modified FOLFOX6 regimen was then delivered for 3 months.. The treatments were generally well tolerated. Dose reduction was recorded in 11 of the 40 patients (27.5 %). The incidence of febrile neutropenia was 5 %, the incidence of grade 3 or 4 asthenia was 10 %, and the incidence of grade 3 gastrointestinal adverse events was 5 % during treatment. Treatment discontinuation caused by toxic effects or any other reasons was observed in six patients (15 %). The reasons for discontinuation were asthenia (n = 2, 5 %), diarrhea (n = 2, 5 %), acute renal failure (n = 1, 2.5 %), and relapse during chemotherapy (n = 1, 2.5 %). With a median follow-up duration of 18 months, six patients (15 %) relapsed and one patient (2.5 %) died of disease progression. The estimated 3-year disease-free survival and overall survival rates were 84.2 and 97.3 %, respectively.. Postoperative adjuvant modified FOLFOX6 regimen was found to be feasible for patients with LARC treated with neoadjuvant CRT.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Chemotherapy, Adjuvant; Feasibility Studies; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Pilot Projects; Rectal Neoplasms; Risk Factors

To investigate prognostic significance of clinical and pathological stages in patients with locally advanced rectal carcinoma treated with neoadjuvant chemoradiotherapy (neo-CRT) and total mesorectal excision.. 210 patients with locally advanced rectal carcinoma (cT3-4 or cN+) treated with neo-CRT followed by total mesorectal excision. Treatment outcomes were compared according to clinical and pathological stage. Overall survival (OS), disease free survival (DFS) among patients with different clinical stage and pathological stage after neo-CRT.. The median follow-up time was 47 months (range, 14-98 months). Clinical T stage was associated with 5 year OS (p = 0.042) and 5 year DFS (p = 0.014) while clinical N stage was not associated with 5 year OS (p = 0.440), 5 year DFS (p = 0.711). Pathological T stage was associate with 5 year OS (p = 0.001) and 5 year DFS (p = 0.046); and N stage was associated with 5 year OS (p = 0.001), 5 year DFS (p = 0.002). The pathological stage was further classified into three groups: ypT0-2N0 in 91 patients (43.3 %), ypT3-4N0 in 69 patients (32.9 %) and ypT0-4N+ in 50 patients (23.8 %). While pathological stage (ypT0-2 vs ypT3-4N0 vs ypT0-4N+) was associated with 5 year OS (87.9 %, 75.5 %, 56.7 %, p = 0.000), 5 year DFS (74.5 %, 77.4 %, 50.5 %, p = 0.003). Multivariate analysis showed that ypN stage was an independent prognostic factor for patients 5 year DFS.. Pathological stage is strongly associated with treatment outcomes in patients with locally advanced rectal carcinoma treated with neo-CRT followed by total mesorectal excision, which may be used as guidance for further individualized treatment.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemoradiotherapy; Combined Modality Therapy; Deoxycytidine; Disease-Free Survival; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Organoplatinum Compounds; Oxaloacetates; Postoperative Complications; Prognosis; Proportional Hazards Models; Radiotherapy, Conformal; Radiotherapy, High-Energy; Rectal Neoplasms; Young Adult

The purpose of this prospective pilot study was to determine the efficacy of preoperative chemotherapy with six cycles of FOLFOX 6 (without radiation therapy) followed by radical surgery followed by six additional cycles of FOLFOX 6 for patients with stage II/III rectal cancer.. From January 2010 to January 2014, patients with locally advanced rectal cancer who met the eligibility criteria were enrolled in this study. Patients received FOLFOX 6 chemotherapy comprising oxaliplatin and leucovorin calcium i.v. over 2 hours on day 1, then bolus, and then continuous fluorouracil i.v. over 46 hours on days 1 and 2. Treatment was repeated every 14 days for 6 courses followed by radical surgery followed by additional 6 cycles of FOLFOX 6.. In total, 45 patients were enrolled in this study. In the preoperative re-evaluation, the overall response rate was 68.8% (clinical complete response was 4.4%, and the partial response was 64.4%). There were 14 cases (31.2%) of stable disease. No patients had progressive disease. Postoperatively, the pathologic complete response rate was 8 of 45 (17.8%; 95% confidence interval [CI]: 8.9%-28.9%). The median follow-up was 29 months (range 9-54 months). The actuarial 3-year overall survival and disease-free survival rates for all patients were 80.8% (standard error, 1.877; 95% CI: 69.3%-92.3%) and 67.9% (standard error, 2.319; 95% CI: 54.3%-81.5%), respectively.. Neoadjuvant chemotherapy (FOLFOX) without radiotherapy is active and safe but cannot be considered a standard of care until the results of prospective randomized phase III trials are available.. Neoadjuvant radiotherapy of rectal cancer represents the current standard of care. However, its use is also associated with short-term toxicity and long-term morbidity. With the increasing use of total mesorectal resection resulting in better local control and advances in systemic therapy for colorectal cancer, this study highlights the question of whether radiation is a necessary component of neoadjuvant therapy for all patients with rectal cancer or whether select patients could be spared the additional toxicities and inconvenience of radiotherapy. This study suggests that neoadjuvant FOLFOX without radiotherapy is active and safe, but it could not be considered a standard of care till now.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Postoperative Care; Prospective Studies; Rectal Neoplasms; Treatment Outcome; Young Adult

To evaluate the rate of gastrointestinal (GI) toxicity of neoadjuvant chemoradiation with capecitabine, oxaliplatin, and intensity modulated radiation therapy (IMRT) in cT3-4 rectal cancer.. Patients with localized, nonmetastatic T3 or T4 rectal cancer <12 cm from the anal verge were enrolled in a prospective, multi-institutional, single-arm study of preoperative chemoradiation. Patients received 45 Gy with IMRT in 25 fractions, followed by a 3-dimensional conformal boost of 5.4 Gy in 3 fractions with concurrent capecitabine/oxaliplatin (CAPOX). Surgery was performed 4 to 8 weeks after the completion of therapy. Patients were recommended to receive FOLFOX chemotherapy after surgery. The primary endpoint of the study was acute grade 2 to 5 GI toxicity. Seventy-one patients provided 80% probability to detect at least a 12% reduction in the specified GI toxicity with the treatment of CAPOX and IMRT, at a significance level of .10 (1-sided).. Seventy-nine patients were accrued, of whom 68 were evaluable. Sixty-one patients (89.7%) had cT3 disease, and 37 (54.4%) had cN (+) disease. Postoperative chemotherapy was given to 42 of 68 patients. Fifty-eight patients had target contours drawn per protocol, 5 patients with acceptable variation, and 5 patients with unacceptable variations. Thirty-five patients (51.5%) experienced grade ≥ 2 GI toxicity, 12 patients (17.6%) experienced grade 3 or 4 diarrhea, and pCR was achieved in 10 patients (14.7%). With a median follow-up time of 3.98 years, the 4-year rate of locoregional failure was 7.4% (95% confidence interval [CI]: 1.0%-13.7%). The 4-year rates of OS and DFS were 82.9% (95% CI: 70.1%-90.6%) and 60.6% (95% CI: 47.5%-71.4%), respectively.. The use of IMRT in neoadjuvant chemoradiation for rectal cancer did not reduce the rate of GI toxicity.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemoradiotherapy, Adjuvant; Deoxycytidine; Diarrhea; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Preoperative Care; Quality of Life; Radiotherapy, Intensity-Modulated; Rectal Neoplasms; Survival Rate

Patients with locally advanced rectal cancer who achieve a pathological complete response to neoadjuvant chemoradiation have an improved prognosis. The need for surgery in these patients has been questioned, but the proportion of patients achieving a pathological complete response is small. We aimed to assess whether adding cycles of mFOLFOX6 between chemoradiation and surgery increased the proportion of patients achieving a pathological complete response.. We did a phase 2, non-randomised trial consisting of four sequential study groups of patients with stage II-III locally advanced rectal cancer at 17 institutions in the USA and Canada. All patients received chemoradiation (fluorouracil 225 mg/m(2) per day by continuous infusion throughout radiotherapy, and 45·0 Gy in 25 fractions, 5 days per week for 5 weeks, followed by a minimum boost of 5·4 Gy). Patients in group 1 had total mesorectal excision 6-8 weeks after chemoradiation. Patients in groups 2-4 received two, four, or six cycles of mFOLFOX6, respectively, between chemoradiation and total mesorectal excision. Each cycle of mFOLFOX6 consisted of racemic leucovorin 200 mg/m(2) or 400 mg/m(2), according to the discretion of the treating investigator, oxaliplatin 85 mg/m(2) in a 2-h infusion, bolus fluorouracil 400 mg/m(2) on day 1, and a 46-h infusion of fluorouracil 2400 mg/m(2). The primary endpoint was the proportion of patients who achieved a pathological complete response, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00335816.. Between March 24, 2004, and Nov 16, 2012, 292 patients were registered, 259 of whom (60 in group 1, 67 in group 2, 67 in group 3, and 65 in group 4) met criteria for analysis. 11 (18%, 95% CI 10-30) of 60 patients in group 1, 17 (25%, 16-37) of 67 in group 2, 20 (30%, 19-42) of 67 in group 3, and 25 (38%, 27-51) of 65 in group 4 achieved a pathological complete response (p=0·0036). Study group was independently associated with pathological complete response (group 4 compared with group 1 odds ratio 3·49, 95% CI 1·39-8·75; p=0·011). In group 2, two (3%) of 67 patients had grade 3 adverse events associated with the neoadjuvant administration of mFOLFOX6 and one (1%) had a grade 4 adverse event; in group 3, 12 (18%) of 67 patients had grade 3 adverse events; in group 4, 18 (28%) of 65 patients had grade 3 adverse events and five (8%) had grade 4 adverse events. The most common grade 3 or higher adverse events associated with the neoadjuvant administration of mFOLFOX6 across groups 2-4 were neutropenia (five in group 3 and six in group 4) and lymphopenia (three in group 3 and four in group 4). Across all study groups, 25 grade 3 or worse surgery-related complications occurred (ten in group 1, five in group 2, three in group 3, and seven in group 4); the most common were pelvic abscesses (seven patients) and anastomotic leaks (seven patients).. Delivery of mFOLFOX6 after chemoradiation and before total mesorectal excision has the potential to increase the proportion of patients eligible for less invasive treatment strategies; this strategy is being tested in phase 3 clinical trials.. National Institutes of Health National Cancer Institute.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Canada; Chemoradiotherapy, Adjuvant; Disease Progression; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Intention to Treat Analysis; Leucovorin; Logistic Models; Male; Middle Aged; Multivariate Analysis; Neoadjuvant Therapy; Neoplasm Staging; Odds Ratio; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms; Remission Induction; Time Factors; Treatment Outcome; United States

We have previously shown that an intensified preoperative regimen including oxaliplatin plus raltitrexed and 5-fluorouracil/folinic acid (OXATOM/FUFA) during preoperative pelvic radiotherapy produced promising results in locally advanced rectal cancer (LARC). Preclinical evidence suggests that the scheduling of bevacizumab may be crucial to optimize its combination with chemo-radiotherapy.. This non-randomized, non-comparative, phase II study was conducted in MRI-defined high-risk LARC. Patients received three biweekly cycles of OXATOM/FUFA during RT. Bevacizumab was given 2 weeks before the start of chemo-radiotherapy, and on the same day of chemotherapy for 3 cycles (concomitant-schedule A) or 4 days prior to the first and second cycle of chemotherapy (sequential-schedule B). Primary end point was pathological complete tumor regression (TRG1) rate.. The accrual for the concomitant-schedule was early terminated because the number of TRG1 (2 out of 16 patients) was statistically inconsistent with the hypothesis of activity (30%) to be tested. Conversely, the endpoint was reached with the sequential-schedule and the final TRG1 rate among 46 enrolled patients was 50% (95% CI 35%-65%). Neutropenia was the most common grade ≥ 3 toxicity with both schedules, but it was less pronounced with the sequential than concomitant-schedule (30% vs. 44%). Postoperative complications occurred in 8/15 (53%) and 13/46 (28%) patients in schedule A and B, respectively. At 5 year follow-up the probability of PFS and OS was 80% (95%CI, 66%-89%) and 85% (95%CI, 69%-93%), respectively, for the sequential-schedule.. These results highlights the relevance of bevacizumab scheduling to optimize its combination with preoperative chemo-radiotherapy in the management of LARC.

Topics: Adult; Aged; Angiogenesis Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Chemoradiotherapy, Adjuvant; Disease Progression; Disease-Free Survival; Drug Administration Schedule; Early Termination of Clinical Trials; Female; Fluorouracil; Humans; Italy; Kaplan-Meier Estimate; Leucovorin; Magnetic Resonance Imaging; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Organoplatinum Compounds; Oxaliplatin; Predictive Value of Tests; Quinazolines; Rectal Neoplasms; Risk Factors; Thiophenes; Time Factors; Treatment Outcome

Treatment of patients with non-metastatic, locally advanced rectal cancer (LARC) includes pre-operative chemoradiation, total mesorectal excision (TME) and post-operative adjuvant chemotherapy. This trimodality treatment provides local tumor control in most patients; but almost one-third ultimately die from distant metastasis. Most survivors experience significant impairment in quality of life (QoL), due primarily to removal of the rectum. A current challenge lies in identifying patients who could safely undergo rectal preservation without sacrificing survival benefit and QoL.. This multi-institutional, phase II study investigates the efficacy of total neoadjuvant therapy (TNT) and selective non-operative management (NOM) in LARC. Patients with MRI-staged Stage II or III rectal cancer amenable to TME will be randomized to receive FOLFOX/CAPEOX: a) before induction neoadjuvant chemotherapy (INCT); or b) after consolidation neoadjuvant chemotherapy (CNCT), with 5-FU or capecitabine-based chemoradiation. Patients in both arms will be re-staged after completing all neoadjuvant therapy. Those with residual tumor at the primary site will undergo TME. Patients with clinical complete response (cCR) will receive non-operative management (NOM). NOM patients will be followed every 3 months for 2 years, and every 6 months thereafter. TME patients will be followed according to NCCN guidelines. All will be followed for at least 5 years from the date of surgery or--in patients treated with NOM--the last day of treatment.. The studies published thus far on the safety of NOM in LARC have compared survival between select groups of patients with a cCR after NOM, to patients with a pathologic complete response (pCR) after TME. The current study compares 3-year disease-free survival (DFS) in an entire population of patients with LARC, including those with cCR and those with pCR. We will compare the two arms of the study with respect to organ preservation at 3 years, treatment compliance, adverse events and surgical complications. We will measure QoL in both groups. We will analyze molecular indications that may lead to more individually tailored treatments in the future. This will be the first NOM trial utilizing a regression schema for response assessment in a prospective fashion.. NCT02008656.

Topics: Adenocarcinoma; Adult; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemoradiotherapy; Consolidation Chemotherapy; Disease-Free Survival; Female; Fluorouracil; Humans; Induction Chemotherapy; Leucovorin; Male; Neoadjuvant Therapy; Organ Sparing Treatments; Organoplatinum Compounds; Oxaliplatin; Prospective Studies; Quality of Life; Rectal Neoplasms

The purpose of this study was to evaluate the rate of pathologic complete response (pCR) in patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiation therapy (CRT) with leucovorin (FL) versus irinotecan/S-1 (IS).. Patients with resectable LARC (clinical stage T3/4, lymph node positive, or both) were randomly assigned to receive preoperative radiation (45-50.4 Gy in 25 to 28 daily fractions) and concomitant chemotherapy either with a bolus injection of FL (400 mg/m(2)/day 5-fluorouracil and 20 mg/m(2)/day leucovorin) for 3 consecutive days every 4 weeks for 2 cycles (FL group) or with 40 mg/m(2) irinotecan on days 1, 8, 15, 22, and 29, and 35 mg/m(2) S-1 twice on the day of irradiation (IS group). Curative surgery was performed approximately 4 to 8 weeks after the completion of CRT. The postoperative chemotherapy regimen was FL with a primary endpoint of a pCR rate evaluation.. One hundred forty-two eligible patients were randomly assigned, and the median follow-up duration was 43.8 months (95% confidence interval, 40.8-46.8 months). One hundred thirty-three patients (93.7%) of 142 underwent total mesorectal excision; pCR was achieved in 11 (16.7%) of 66 patients in the FL group and 17 (25.8%) of 67 patients in the IS group (P=.246). When good responders were defined as patients with Mandard grades 1 and 2, the rate of good responders was significantly higher in the IS group than in the FL group (54.6% vs 36.4%, respectively, P=.036). The preoperative rates of grade 3 and 4 toxicities were higher in the IS group (7.0%) than in the FL group (1.4%, P=.095). The 3-year disease-free survival was not significantly different between the 2 groups (79.7% vs 76.6%, respectively, P=.896).. IS-based preoperative CRT did not increase pCR rate, but it did increase acute toxicities compared with standard 5-FU treatment. Therefore, further investigation is needed.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemoradiotherapy, Adjuvant; Chi-Square Distribution; Confidence Intervals; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Fluorouracil; Humans; Induction Chemotherapy; Irinotecan; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Rectal Neoplasms; Tegafur

Current evidence supports a diverting stoma in patients undergoing low anterior resection with total mesorectal excision for rectal cancer as it reduces clinical severity of anastomotic leakage. However, relevant stoma morbidity after rectal cancer surgery exists and has a significant impact on quality of life. Moreover, a diverting stoma has an influence on completeness of chemotherapy but it remains unclear in which way. There is no evidence regarding optimal timing for stoma closure in relation to adjuvant chemotherapy. Two randomised controlled trials have studied early stoma closure after low anterior resection in patients with rectal cancer, one of them showing that early closure around day 8 after resection is possible without increasing morbidity.. CoCStom is a randomised multicentre trial comparing completeness of adjuvant chemotherapy as primary endpoint after early (8-10 days after resection, before starting adjuvant therapy) versus late (~26 weeks after resection and completion of adjuvant therapy) stoma closure in patients with locally advanced rectal cancer undergoing low anterior resection after neoadjuvant therapy. After exclusion of post-operative anastomotic leakage 257 patients from 30 German hospitals are planned to be included in order to assure a power of 80% for the confirmatory analysis of at least 214 evaluable cases. An absolute increase of 20% for the rate of completely administered adjuvant chemotherapy is regarded as a clinically meaningful step forward and serves as basis for sample size calculation. Quality of life, stoma-related complications, individual completeness of chemotherapy rate, percentage of patients stopping adjuvant therapy or undergoing dose modifications or delay, oncological outcomes, cumulative days of hospitalisation and number of readmissions, rate of symptomatic anastomotic leaks after stoma closure, mortality, post-operative complications and toxicity of adjuvant chemotherapy are secondary endpoints.. The CoCStom trial aims to clarify optimal timing of stoma closure in the context of adjuvant chemotherapy. Depending on the results of the trial, patients could benefit either from early or late stoma closure in regard to long term oncological survival due to a higher rate of completeness of adjuvant chemotherapy treatment and thus better effectiveness.. German Clinical Trials Register, DRKS00005113. Registered 28 August 2013.

Topics: Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemotherapy, Adjuvant; Digestive System Surgical Procedures; Female; Fluorouracil; Humans; Leucovorin; Male; Organoplatinum Compounds; Oxaliplatin; Quality of Life; Rectal Neoplasms; Time Factors; Treatment Outcome

To report the results of a phase II trial combining celecoxib and preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer.. Patients with clinical stage II or III rectal cancer were treated with radiotherapy of 44 Gy in 22 fractions. Concurrent chemotherapy consisted of oral tegafur-uracil and folinate on days 1-30 and 38-65. Celecoxib (400 mg/day) given from days 1 to 65. Surgery was done on day 70. The expression of cyclooxygenase 2 (COX-2) in tumor tissues was evaluated microscopically as a prognostic factor.. From 2008 to 2011, 53 patients completed CRT+ celecoxib therapy and 47 received radical surgery. Grade 3 diarrhea developed in 5 (9%). Grade 4 anemia was seen in 2 (4%). Pathological complete response (pCR) was seen in 6 (13%). T or N downstaging found in 38 (81%). Sphincter preservation was achieved in 77% of low-positioned tumors. Patients with tumors expressing high-level COX-2 after CRT + celecoxib treatment had inferior pelvic control (P = 0.01), disease-free survival (P = 0.04), and overall survival (P = 0.03) than those with low-level expression.. Celecoxib can be safely combined with preoperative CRT for rectal cancer. More intensified adjuvant therapy may be considered for tumors expressing high-level COX-2 after CRT and surgery.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Celecoxib; Chemoradiotherapy, Adjuvant; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Disease-Free Survival; Dose Fractionation, Radiation; Female; Humans; Immunohistochemistry; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoadjuvant Therapy; Prognosis; Pyrazoles; Rectal Neoplasms; Rectum; Sulfonamides; Tegafur; Uracil

Although neoadjuvant chemoradiotherapy achieves low local recurrence rates in clinical stages II to III rectal cancer, it delays administration of optimal chemotherapy. We evaluated preoperative infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX)/bevacizumab with selective rather than consistent use of chemoradiotherapy.. Thirty-two patients with clinical stages II to III rectal cancer participated in this single-center phase II trial. All were candidates for low anterior resection with total mesorectal excision (TME). Patients were to receive six cycles of FOLFOX, with bevacizumab included for cycles 1 to 4. Patients with stable/progressive disease were to have radiation before TME, whereas responders were to have immediate TME. Postoperative radiation was planned if R0 resection was not achieved. Postoperative FOLFOX × 6 was recommended, but adjuvant regimens were left to clinician discretion. The primary outcome was R0 resection rate.. Between April 2007 and December 2008, 32 (100%) of 32 study participants had R0 resections. Two did not complete preoperative chemotherapy secondary to cardiovascular toxicity. Both had preoperative chemoradiotherapy and then R0 resections. Of 30 patients completing preoperative chemotherapy, all had tumor regression and TME without preoperative chemoradiotherapy. The pathologic complete response rate to chemotherapy alone was 8 of 32 (25%; 95% CI, 11% to 43%). The 4-year local recurrence rate was 0% (95% CI, 0% to 11%); the 4-year disease-free survival was 84% (95% CI, 67% to 94%).. For selected patients with clinical stages II to III rectal cancer, neoadjuvant chemotherapy and selective radiation does not seem to compromise outcomes. Preoperative Radiation or Selective Preoperative Radiation and Evaluation Before Chemotherapy and TME (PROSPECT), a randomized phase III trial to validate this experience, is now open in the US cooperative group network.

Topics: Adenocarcinoma; Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Chemoradiotherapy, Adjuvant; Chemotherapy, Adjuvant; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Pilot Projects; Radiotherapy, Adjuvant; Rectal Neoplasms; Survival Rate; Treatment Outcome

EORTC trial 22921 examined the addition of preoperative or postoperative chemotherapy to preoperative radiotherapy in patients with rectal cancer. After a median follow-up of 5 years, chemotherapy-irrespective of timing-significantly improved local control. Adjuvant chemotherapy did not improve survival, but the Kaplan-Meier curves diverged, suggesting possible delayed benefit. Here, we report the updated long-term results.. We randomly assigned patients with clinical stage T3 or T4 resectable rectal cancer to receive preoperative radiotherapy with or without concomitant chemotherapy before surgery followed by either adjuvant chemotherapy or surveillance. Randomisation was done using minimisation with factors of institution, sex, T stage, and distance from the tumour to the anal verge. Study coordinators, clinicians, and patients were aware of assignment. Radiotherapy consisted of 45 Gy to the posterior pelvis in 25 fractions of 1·8 Gy over 5 weeks. Each course of chemotherapy consisted of fluorouracil (350 mg/m(2) per day intravenous bolus) and folinic acid (leucovorin; 20 mg/m(2) per day intravenous bolus). For preoperative chemotherapy, two courses were given (during weeks 1 and 5 of radiotherapy). Adjuvant chemotherapy was given in four cycles, every 3 weeks. The primary endpoint was overall survival. This analysis was done by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00002523.. 1011 patients were randomly assigned to treatment between April, 1993, and March, 2003 (252 to preoperative radiotherapy and 253 to each of the other three groups). After a median follow-up of 10·4 years (IQR 7·8-13·1), 10-year overall survival was 49·4% (95% CI 44·6-54·1) for the preoperative radiotherapy group and 50·7% (45·9-55·2) for the preoperative radiotherapy and chemotherapy group (HR 0·99, 95% CI 0·83-1·18; p=0·91). 10-year overall survival was 51·8% (95% CI 47·0-56·4) for the adjuvant chemotherapy group and 48·4% (43·6-53·0) for the surveillance group (HR 0·91, 95% CI 0·77-1·09, p=0·32). 10-year disease-free survival was 44·2% (95% CI 39·5-48·8) for the preoperative radiotherapy group and 46·4% (41·7-50·9) for the preoperative radiotherapy and chemotherapy group (HR 0·93, 95% CI 0·79-1·10; p=0·38). 10-year disease-free survival was 47·0% (95% CI 42·2-51·6) for the adjuvant chemotherapy group and 43·7% (39·1-48·2) for the surveillance group (HR 0·91, 95% CI 0·77-1·08, p=0·29). At 10 years, cumulative incidence of local relapse was 22·4% (95% CI 17·1-27·6) with radiotherapy alone, 11·8% (7·8-15·8) with neoadjuvant radiotherapy and chemotherapy, 14·5% (10·1-18·9) with radiotherapy and adjuvant chemotherapy and 11·7% (7·7-15·6) with both adjuvant and neoadjuvant chemotherapy (p=0·0017). There was no difference in cumulative incidence of distant metastases (p=0·52). The frequency of long-term side-effects did not differ between the four groups (p=0·22).. Adjuvant fluorouracil-based chemotherapy after preoperative radiotherapy (with or without chemotherapy) does not affect disease-free survival or overall survival. Our trial does not support the current practice of adjuvant chemotherapy after preoperative radiotherapy with or without chemotherapy. New treatment strategies incorporating neoadjuvant chemotherapy are required.. EORTC, US National Cancer Institute, Programme Hospitalier de Recherche Clinique, Ligue contre le Cancer Comité du Doubs.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Chemotherapy, Adjuvant; Digestive System Surgical Procedures; Disease Progression; Disease-Free Survival; Europe; Female; Fluorouracil; Humans; Intention to Treat Analysis; Israel; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Proportional Hazards Models; Rectal Neoplasms; Risk Factors; Survival Rate; Time Factors; Treatment Outcome; Young Adult

Preoperative radiation therapy with 5-fluorouracil chemotherapy is a standard of care for cT3-4 rectal cancer. Studies incorporating additional cytotoxic agents demonstrate increased morbidity with little benefit. We evaluate a template that: (1) includes the benefits of preoperative radiation therapy on local response/control; (2) provides preoperative multidrug chemotherapy; and (3) avoids the morbidity of concurrent radiation therapy and multidrug chemotherapy.. Patients with cT3-4, any N, any M rectal cancer were eligible. Patients were confirmed to be candidates for pelvic surgery, provided response was sufficient. Preoperative treatment was 5 fractions radiation therapy (25 Gy to involved mesorectum, 20 Gy to elective nodes), followed by 4 cycles of FOLFOX [5-fluorouracil, oxaliplatin, leucovorin]. Extirpative surgery was performed 4 to 9 weeks after preoperative chemotherapy. Postoperative chemotherapy was at the discretion of the medical oncologist. The principal objectives were to achieve T stage downstaging (ypT < cT) and preoperative grade 3+ gastrointestinal morbidity equal to or better than that of historical controls.. 76 evaluable cases included 7 cT4 and 69 cT3; 59 (78%) cN+, and 7 cM1. Grade 3 preoperative GI morbidity occurred in 7 cases (9%) (no grade 4 or 5). Sphincter-preserving surgery was performed on 57 (75%) patients. At surgery, 53 patients (70%) had ypT0-2 residual disease, including 21 (28%) ypT0 and 19 (25%) ypT0N0 (complete response); 24 (32%) were ypN+. At 30 months, local control for all evaluable cases and freedom from disease for M0 evaluable cases were, respectively, 95% (95% confidence interval [CI]: 89%-100%) and 87% (95% CI: 76%-98%). Cases were subanalyzed by whether disease met requirements for the recently activated PROSPECT trial for intermediate-risk rectal cancer. Thirty-eight patients met PROSPECT eligibility and achieved 16 ypT0 (42%), 15 ypT0N0 (39%), and 33 ypT0-2 (87%).. This regimen achieved response and morbidity rates that compare favorably with those of conventionally fractionated radiation therapy and concurrent chemotherapy.

Topics: Anal Canal; Antineoplastic Combined Chemotherapy Protocols; Dose Fractionation, Radiation; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Neoplasm, Residual; Organ Sparing Treatments; Organoplatinum Compounds; Preoperative Care; Prospective Studies; Pyridines; Rectal Neoplasms

To assess the long-term outcomes of patients with rectal cancer who received neoadjuvant chemoradiation therapy (NCRT) with concurrent S-1 and irinotecan (S-1/irinotecan) therapy.. The study group consisted of 115 patients with clinical stage T3 or T4 rectal cancer. Patients received pelvic radiation therapy (45 Gy) plus concurrent oral S-1/irinotecan. The median follow-up was 60 months.. Grade 3 adverse effects occurred in 7 patients (6%), and the completion rate of NCRT was 87%. All 115 patients (100%) were able to undergo R0 surgical resection. Twenty-eight patients (24%) had a pathological complete response (ypCR). At 60 months, the local recurrence-free survival was 93%, disease-free survival (DFS) was 79%, and overall survival (OS) was 80%. On multivariate analysis with a proportional hazards model, ypN2 was the only independent prognostic factor for DFS (P=.0019) and OS (P=.0064) in the study group as a whole. Multivariate analysis was additionally performed for the subgroup of 106 patients with ypN0/1 disease, who had a DFS rate of 85.3%. Both ypT (P=.0065) and tumor location (P=.003) were independent predictors of DFS. A combination of these factors was very strongly related to high risk of recurrence (P<.0001), which occurred most commonly in the lung.. NCRT with concurrent S-1/irinotecan produced high response rates and excellent long-term survival, with acceptable adverse effects in patients with rectal cancer. ypN2 is a strong predictor of dismal outcomes, and a combination of ypT and tumor location can identify high-risk patients among those with ypN0/1 disease.

Topics: Adult; Aged; Aged, 80 and over; Agranulocytosis; Analysis of Variance; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemoradiotherapy; Diarrhea; Disease-Free Survival; Dose Fractionation, Radiation; Drug Administration Schedule; Drug Combinations; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Leukopenia; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Oxonic Acid; Rectal Neoplasms; Tegafur; Treatment Outcome

Mature data on tumor control and survival are presented from a randomized trial of the addition of a brachytherapy boost to long-course neoadjuvant chemoradiation therapy (CRT) for locally advanced rectal cancer.. Between March 2005 and November 2008, 248 patients with T3-4N0-2M0 rectal cancer were prospectively randomized to either long-course preoperative CRT (50.4 Gy in 28 fractions, per oral tegafur-uracil and L-leucovorin) alone or the same CRT schedule plus a brachytherapy boost (10 Gy in 2 fractions). The primary trial endpoint was pathologic complete response (pCR) at the time of surgery; secondary endpoints included overall survival (OS), progression-free survival (PFS), and freedom from locoregional failure.. Results for the primary endpoint have previously been reported. This analysis presents survival data for the 224 patients in the Danish part of the trial. In all, 221 patients (111 control arm, 110 brachytherapy boost arm) had data available for analysis, with a median follow-up time of 5.4 years. Despite a significant increase in tumor response at the time of surgery, no differences in 5-year OS (70.6% vs 63.6%, hazard ratio [HR] = 1.24, P=.34) and PFS (63.9% vs 52.0%, HR=1.22, P=.32) were observed. Freedom from locoregional failure at 5 years were 93.9% and 85.7% (HR=2.60, P=.06) in the standard and in the brachytherapy arms, respectively. There was no difference in the prevalence of stoma. Explorative analysis based on stratification for tumor regression grade and resection margin status indicated the presence of response migration.. Despite increased pathologic tumor regression at the time of surgery, we observed no benefit on late outcome. Improved tumor regression does not necessarily lead to a relevant clinical benefit when the neoadjuvant treatment is followed by high-quality surgery.

Topics: Adult; Aged; Algorithms; Antineoplastic Combined Chemotherapy Protocols; Brachytherapy; Chemoradiotherapy, Adjuvant; Denmark; Disease-Free Survival; Female; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Prospective Studies; Radiotherapy, Conformal; Rectal Neoplasms; Tegafur; Uracil

In T3 rectal cancer (RC), preoperative chemoradiotherapy [5-fluorouracil (5-FU-RT)] reduces local recurrences, but does not affect overall survival. New therapeutic options are still necessary to improve clinical outcomes.. This randomized, noncomparative, open-label, multicenter, two arms, phase II study was conducted in MRI-defined locally advanced T3 resectable RC. In arm A, patients received 12-week bevacizumab plus 5-FU, leucovorin and oxaliplatin (Folfox-4) followed with bevacizumab-5-FU-RT before total mesorectal excision (TME). In arm B, patients received only bevacizumab-5-FU-RT before TME. Primary end point was pathological complete response (pCR) rate.. Forty-six patients were randomized in arm A and 45 patients in arm B. In arm A, the rate of pCR was 23.8% [95% confidence interval (CI) 12.1% to 39.5%] statistically superior to the defined standard rate of 10%, P = 0.015. In arm B, the rate of pCR of 11.4% (95% CI 3.8% to 24.6%) was not different from 10%, P = 0.906. No death occurred during the study period, from the start until 8 weeks following surgery. Postoperative fistulas were reported for 16 patients (7 in arm A and 9 in arm B).. Even if the addition of bevacizumab induced manageable toxicities including an increased risk of postoperative fistula and no treatment-related death, arm B did not achieve the expected pCR rate in the population of patients included. Induction bevacizumab-Folfox-4 followed by bevacizumab-5-FU-RT is promising. It is however necessary to continue investigations in the management of locally advanced RC. ClinicalTrials.gov Identifier: NCT 00865189.

Topics: Adolescent; Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Deoxycytidine; Digestive System Surgical Procedures; Female; Fluorouracil; Humans; Leucovorin; Magnetic Resonance Imaging; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms

The role of adjuvant chemotherapy for patients with rectal cancer is controversial, especially when used after preoperative chemoradiotherapy. Fluoropyrimidine-based adjuvant chemotherapy, including fluorouracil and leucovorin, has been widely used; however, the addition of oxaliplatin to fluorouracil and leucovorin (FOLFOX), a standard adjuvant regimen for colon cancer, has not been tested in rectal cancer. We aimed to compare the efficacy and safety of adjuvant fluorouracil and leucovorin with that of FOLFOX in patients with locally advanced rectal cancer after preoperative chemoradiotherapy.. In this open-label, multicentre, phase 2, randomised trial, patients with postoperative pathological stage II (ypT3-4N0) or III (ypTanyN1-2) rectal cancer after preoperative fluoropyrimidine-based chemoradiotherapy and total mesorectal excision were recruited and randomly assigned (1:1) via a web-based software platform to receive adjuvant chemotherapy with either four cycles of fluorouracil and leucovorin (fluorouracil 380 mg/m(2) and leucovorin 20 mg/m(2) on days 1-5, every 4 weeks) or eight cycles of FOLFOX (oxaliplatin 85 mg/m(2), leucovorin 200 mg/m(2), and fluorouracil bolus 400 mg/m(2) on day 1, and fluorouracil infusion 2400 mg/m(2) for 46 h, every 2 weeks). Stratification factors were pathological stage (II vs III) and centre. Neither patients nor investigators were masked to group assignment. The primary endpoint was 3-year disease-free survival, analysed by intention to treat. This study is fully enrolled, is in long-term follow-up, and is registered with ClinicalTrials.gov, number NCT00807911.. Between Nov 19, 2008, and June 12, 2012, 321 patients were randomly assigned to fluorouracil and leucovorin (n=161) and FOLFOX (n=160). 141 (95%) of 149 patients in the fluorouracil plus leucovorin group and 141 (97%) of 146 in the FOLFOX group completed all planned cycles of adjuvant treatment. Median follow-up was 38·2 months (IQR 26·4-50·6). 3-year disease-free survival was 71·6% (95% CI 64·6-78·6) in the FOLFOX group and 62·9% (55·4-70·4) in the fluorouracil plus leucovorin group (hazard ratio 0·657, 95% CI 0·434-0·994; p=0·047). Any grade neutropenia, thrombocytopenia, fatigue, nausea, and sensory neuropathy were significantly more common in the FOLFOX group than in the fluorouracil plus leucovorin group; however, we noted no significant difference in the frequency of these events at grade 3 or 4. The most common grade 3 or worse adverse events were neutropenia (38 [26%] of 149 patients in the fluorouracil plus leucovorin group vs 52 [36%] of 146 patients in the FOLFOX group), leucopenia (eight [5%] vs 12 [8%]), febrile neutropenia (four [3%] vs one [<1%]), diarrhoea (four [3%] vs two [1%]), and nausea (one [<1%] vs two [1%]).. Adjuvant FOLFOX improves disease-free survival compared with fluorouracil plus leucovorin in patients with locally advanced rectal cancer after preoperative chemoradiotherapy and total mesorectal excision, and warrants further investigation.. Korea Healthcare Technology R&D Project (South Korean Ministry of Health and Welfare).

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Chemotherapy, Adjuvant; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Maximum Tolerated Dose; Middle Aged; Neoadjuvant Therapy; Neoplasm Invasiveness; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Preoperative Care; Prognosis; Rectal Neoplasms; Survival Analysis; Taiwan; Treatment Outcome

Patients (pts) with metastatic rectal cancer and symptomatic primary, require local and systemic control. Chemotherapy used during chemoradiotherapy (CRT) is adequate for radiosensitisation, but suboptimal for systemic control. The aim of this phase II study was to assess tolerability, local/systemic benefits, of a novel regimen delivering interdigitating intensive chemotherapy with radical CRT.. Eligible pts had untreated synchronous symptomatic primary/metastatic rectal cancer. A total of 12 weeks of treatment with split-course pelvic CRT (total 50.4 Gy with concurrent oxaliplatin and 5-FU infusion) alternating with FOLFOX chemotherapy. All pts staged with CT, MRI and FDG-PET pre and post treatment.. Twenty-six pts were treated. Rectal primary MRI stage: T3 81% and T4 15%. Liver metastases in 81%. Twenty-four pts (92%) completed the 12-week regimen. All patients received planned RT dose, and for both agents over 88% of patients achieved a relative dose intensity of >75%. Grade 3 toxicities: neutropenia 23%, diarrhoea 15%, and radiation skin reaction 12%. Grade 4 toxicity: neutropenia 15%. FDG-PET metabolic response rate for rectal primary 96%, and for metastatic disease 60%.. Delivery of interdigitating chemotherapy with radical CRT was feasible to treat both primary and metastatic rectal cancer. High completion and response rates were encouraging.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Cohort Studies; Feasibility Studies; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Pelvic Neoplasms; Prognosis; Radiotherapy Dosage; Rectal Neoplasms; Survival Rate

To evaluate the effect of adjuvant chemotherapy (ACT) in locally advanced rectal cancer (LARC) after neoadjuvant chemoradiation (NACT-RT). The study was funded by the Italian National Research Council (CNR).. From September 1992 to January 2001, 655 patients with LARC (clinically T3-4, any N) treated with NACT-RT and surgery, were randomized in two arms: follow-up (Arm A) or 6 cycles of ACT with 5 fluorouracil (5FU)-Folinic Acid (Arm B). NACT-RT consisted of 45Gy/28/ff concurrent with 5FU (350mg/sqm) and Folinic Acid (20mg/sqm) on days 1-5 and 29-33; surgery was performed after 4-6weeks. Median follow up was 63·7months. Primary end point was overall survival (OS).. 634/655 patients were evaluable (Arm A 310, Arm B 324); 92·5% of Arm A and 91% of Arm B patients received the preoperative treatment as in the protocol; 294 patients of Arm A (94·8%) and 296 of Arm B (91·3%) underwent a radical resection; complete pathologic response and overall downstaging rates did not show any significant difference in the two arms. 83/297 (28%) patients in Arm B, never started ACT. Five year OS and DFS did not show any significant difference in the two treatment arms. Distant metastases occurred in 62 patients (21%) in Arm A and in 58 (19·6%) in Arm B.. In patients with LARC treated with NACT-RT, the addition of ACT did not improve 5year OS and DFS and had no impact on the distant metastasis rate.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Chemotherapy, Adjuvant; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Rectal Neoplasms; Treatment Outcome

To present an interim analysis of the trial comparing two neoadjuvant therapies for unresectable rectal cancer.. Patients with fixed cT3 or cT4 or locally recurrent rectal cancer without distant metastases were randomized to either 5 × 5 Gy and 3 courses of FOLFOX4 (schedule I) or 50.4 Gy delivered in 28 fractions given simultaneously with 5-Fu, leucovorin and oxaliplatin (schedule II). Surgery in both groups was performed 12 weeks after the beginning of radiation and 6 weeks after neoadjuvant treatment.. 49 patients were treated according to schedule I and 48 according to schedule II. Grade III+ acute toxicity was observed in 26% of patients in group I and in 25% in group II. There were two toxic deaths, both in group II. The microscopically radical resection (primary endpoint) rate was 73% in group I and 71% in group II. Overall and severe postoperative complications were recorded in 27% and 9% of patients vs. 16% and 7%, respectively. Pathological complete response was observed in 21% of the patients in group I and in 9% in group II.. The interim analysis revealed no major differences in acute toxicity and local efficacy between the two evaluated strategies.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Rectal Neoplasms

In selected patients with rectal cancer, laparoscopic surgery is as safe as open surgery, with similar resection margins and completeness of resection. In addition, recovery is faster after laparoscopic surgery. We analyzed long-term outcomes in a group of patients with locally advanced rectal cancer (LARC) treated with preoperative therapy followed by laparoscopic surgery and intraoperative electron-beam radiotherapy (IOERT).. From June 2005 to December 2010, 125 LARC patients were treated with 2 induction courses of FOLFOX-4 (oxaliplatin 85 mg/m(2)/d1, intravenous leucovorin at 200 mg/m(2)/d1-2, and an intravenous bolus of 5-fluorouracil 400 mg/m(2)/d1-2) and preoperative chemoradiation (4,500-5,040 cGy) followed by total mesorectal excision (laparoscopic, 35 %; open surgery, 65 %) and a presacral boost with IOERT.. Patients in the laparoscopic surgery group lost less blood (median 200 vs 350 mL, p < 0.01) and had a shorter hospital stay (7 vs 11 days; p = 0.02) than those in the open surgery group. Laparoscopic procedures were shorter than open surgery procedures (270 vs 302 min; p = 0.67). Postoperative morbidity (32 vs 44 %; p = 0.65), RTOG grade ≥3 acute toxicity (25 vs 25 %; p = 0.97), and RTOG grade ≥3 chronic toxicity (7 vs 9 %; p = 0.48) were similar in the laparoscopy and open surgery groups. The median follow-up time for the entire cohort of patients was 59.5 months (range 7.8-90); no significant differences were observed between the groups in locoregional control (HR 0.91, p = 0.89), disease-free survival (HR 0.80, p = 0.65), and overall survival (HR 0.67, p = 0.52).. Postchemoradiation laparoscopically assisted IOERT is feasible, with an acceptable risk of postoperative complications, shorter hospital stay, and similar long-term outcomes when compared to the open surgery approach.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Female; Fluorouracil; Follow-Up Studies; Humans; International Cooperation; Intraoperative Care; Laparoscopy; Leucovorin; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Radiotherapy; Rectal Neoplasms

No immediate surgery (Watch and Wait) has been considered in select patients with complete clinical response after neoadjuvant chemoradiation to avoid postoperative morbidity and functional disorders after radical surgery.. The purpose of this study was to demonstrate the long-term results of patients who had a complete clinical response following an alternative chemoradiation regimen and were managed nonoperatively.. This is a prospective study.. This study was conducted at a single center.. Seventy consecutive patients with T2-4N0-2M0 distal rectal cancer were studied. Neoadjuvant chemoradiotherapy included 54 Gy and 5-fluorouracil/leucovorin delivered in 6 cycles every 21 days. Patients were assessed for tumor response at 10 weeks from radiation completion. Patients with incomplete clinical response were referred to immediate surgery. Patients with complete clinical response were not immediately operated on and were monitored.. The primary outcomes measured were the initial complete clinical response rates after 10 weeks and the sustained complete clinical response rates after 12 months from chemoradiotherapy.. One patient died during chemoradiotherapy because of cardiac complications. Forty-seven (68%) patients had initial complete clinical response. Of these, 8 developed local regrowth within the first 12 months of follow-up (17%). Thirty-nine sustained complete clinical response at a median follow-up of 56 months (57%). An additional 4 patients (10%) developed late local recurrences (>12 months of follow-up). Overall, 35 patients never underwent surgery (50%).. This study is limited by the short follow-up and small sample size.. Extended chemoradiation therapy with additional chemotherapy cycles and 54 Gy of radiation may result in over 50% of sustained (>12 months) complete clinical response rates that may ultimately avoid radical rectal resection. Local failures occur more frequently during the initial 12 months of follow-up in up to 17% of cases, whereas late recurrences are less common but still possible, leading to 50% of patients who never required surgery. Strict follow-up may allow salvage therapy in the majority of these patients (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A113.).

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Dose Fractionation, Radiation; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Prospective Studies; Rectal Neoplasms; Time Factors; Watchful Waiting

To evaluate the safety and efficacy of neoadjuvant chemoradiation with oxaliplatin and 5-fluorouracil (5-FU) in advanced mid-to-lower rectal cancer.. This was a single-arm, open-label phase II study conducted between August 2008 and August 2010. Thirty-one patients (n = 31) with clinical stage T3/T4 or lymph node positive rectal adenocarcinoma located in the middle or lower rectum without metastasis were enrolled onto the study. Data were analyzed according to the intention-to-treat principle.. Thirty-one patients were enrolled into the study. Six patients (19.4%) experienced grade 3 diarrhea. Grade 2 nausea and vomiting occurred in 5 and 2 patients, respectively. Severe neurotoxicity was not observed. Grade 1 sensory neuropathy occurred in 10 patients (32.3%). Sphincter-saving surgery was performed in 29 patients (93.5%). The mean distance of the tumor from the anal verge was 4.9 cm. Anastomotic leakage occurred in 4 of 29 (13.8%) patients. The circumferential resection margin was involved in 2 patients (6.5%). Overall, 23 patients (77.4%) responded to treatment. The complete pathologic response (ypCR) rate was 12.9%. There was no death secondary to toxicity, and the mean follow-up time was 12.3 months.. The overall toxicity of oxaliplatin and continuous 5-FU/leucovorin infusion in combination with radiation was well tolerated. Neoadjuvant chemoradiation for patients with locally advanced rectal cancer was associated with higher rates of sphincter preservation and downstaging, but did not significantly increase ypCR. The impact of this neoadjuvant chemoradiation regimen on survival will be determined by longer follow-up studies.

Topics: Adult; Aged; Combined Modality Therapy; Female; Fluorouracil; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaliplatin; Radiotherapy Dosage; Rectal Neoplasms; Treatment Outcome

Two identical randomized controlled trials designed to optimize adjuvant treatment of colon cancer (CC) (n =855) and rectal cancer (RC) (n = 796) were performed. Long-term evaluation confirmed that the addition of folinic acid (FA) to 5-fluorouracil (5-FU) improved 7-year overall survival (OS) in CC but not in RC and revealed different patterns of recurrence in patients with CC and those with RC.. Our aim was to compare long-term results of adjuvant treatment of colon cancer (CC) and rectal cancer (RC). Adjuvant chemotherapy of CC improved overall survival (OS), whereas that of RC remained at the level achieved by 5-fluorouracil (5-FU).. We separately conducted 2 identically designed adjuvant trials in CC and RC. Patients were assigned to adjuvant chemotherapy with 5-FU alone, 5-FU + folinic acid (FA), or 5-FU + interferon-alfa. The first study enrolled patients with stage IIb/III CC, and the second study enrolled patients with stage II/III RC. All patients with RC received postoperative irradiation.. Median follow-up for all patients with CC (n = 855) and RC (n = 796) was 4.9 years. The pattern and frequency of recurrence differed significantly, especially lung metastases, which occurred more frequently in RC (12.7%) than in CC (7.3%; P < .001). Seven-year OS rates for 5-FU, 5-FU + FA, and 5-FU + IFN-alfa were 54.1% (95% confidence interval [CI], 46.5-61.0), 66.8% (95% CI, 59.4-73.1), and 56.7% (95% CI, 49.3-63.4) in CC and 50.6% (95% CI, 43.0-57.7), 56.3% (95% CI, 49.4-62.7), and 54.8% (95% CI, 46.7-62.2) in RC, respectively. A subgroup analysis pointed to a reduced local recurrence (LR) rate and an increased OS by the addition of FA in stage II RC (n = 271) but not in stage III RC (n = 525).. FA increased 7-year OS by 12.7 percentage points in CC but was not effective in RC. Based on these results and the pattern of metastases, our results suggest that the chemosensitivity of CC and RC may be different. Strategies different from those used in CC may be successful to decrease the frequency of distant metastases in RC in the future.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colonic Neoplasms; Female; Fluorouracil; Follow-Up Studies; Humans; Immunologic Factors; Interferon-alpha; Leucovorin; Liver Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Peritoneal Neoplasms; Prognosis; Prospective Studies; Rectal Neoplasms; Survival Rate

The objective of this study was to report on the quality of life of locally advanced rectal cancer patients that were treated with uracil-tegafur (UFT)/leucovorin (LV)-based concurrent chemoradiotherapy.. Twenty-five patients were enrolled into this prospective study. Radiotherapy (50.4Gy) was given with concurrent UFT (300mg/m2/day) and LV (30mg/day). Turkish versions of EORTC-QLQC30 and EORTC QLQCR38 were applied at the beginning (HRQoL-1) and at the end (HRQoL-2) of chemoradiotherapy. Paired samples t-test was used to compare the difference of means for each scale between HRQoL1 and HRQoL2 and p values <0.05 were considered statistically significant.. Study compliance was 80.6%. From baseline to the end of chemoradiotherapy, the mean scores of dyspnea (p=0.006) diarrhea (p=0.005) and micturition (p=0.005) increased significantly. Chemotherapy side effects also increased at the end of therapy (p=0.07). Seventy-six percent (76%) of male patients replied to questions related to sexual problems and functions, whereas no female patients replied.. Although, diarrhea and micturition are the major problems, quality of life scores indicate that concurrent oral fluoropyrimidine-based chemoradiotherapy is a feasible treatment.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Diarrhea; Female; Humans; Leucovorin; Male; Middle Aged; Postoperative Care; Prospective Studies; Quality of Life; Radiotherapy Dosage; Rectal Neoplasms; Sexual Dysfunction, Physiological; Surveys and Questionnaires; Tegafur; Time Factors; Treatment Outcome; Turkey; Urination Disorders; Young Adult

A prospective phase 2 multicenter trial was performed to investigate the efficacy and safety of preoperative short-course concurrent chemoradiation therapy (CRT) followed by delayed surgery for patients with locally advanced rectal cancer.. Seventy-three patients with cT3-4 rectal cancer were enrolled. Radiation therapy of 25 Gy in 5 fractions was delivered over 5 consecutive days using helical tomotherapy. Concurrent chemotherapy was administered on the same 5 days with intravenous bolus injection of 5-fluorouracil (400 mg/m(2)/day) and leucovorin (20 mg/m(2)/day). After 4 to 8 weeks, total mesorectal excision was performed. The primary endpoint was the pathologic downstaging (ypStage 0-I) rate, and secondary endpoints included tumor regression grade, tumor volume reduction rate, and toxicity.. Seventy-one patients completed the planned preoperative CRT and surgery. Downstaging occurred in 20 (28.2%) patients, including 1 (1.4%) with a pathologic complete response. Favorable tumor regression (grade 4-3) was observed in 4 (5.6%) patients, and the mean tumor volume reduction rate was 62.5 ± 21.3%. Severe (grade ≥3) treatment toxicities were reported in 27 (38%) patients from CRT until 3 months after surgery.. Preoperative short-course concurrent CRT followed by delayed surgery for patients with locally advanced rectal cancer demonstrated poor pathologic responses compared with conventional long-course CRT, and it yielded considerable toxicities despite the use of an advanced radiation therapy technique.

Topics: Adenocarcinoma; Adult; Aged; Antimetabolites, Antineoplastic; Chemoradiotherapy; Dose Fractionation, Radiation; Female; Fluorouracil; Humans; Leucovorin; Lymph Node Excision; Male; Middle Aged; Neoplasm Staging; Preoperative Care; Prospective Studies; Radiotherapy, Intensity-Modulated; Rectal Neoplasms; Treatment Outcome

Recent studies have demonstrated the feasibility of combining oxaliplatin with 5-fluorouracil (5-FU) or capecitibine and radiation therapy. The addition of bevacizumab to chemotherapy improves overall survival for metastatic disease. We initiated a phase 2 trial to evaluate preoperative capecitabine, oxaliplatin, and bevacizumab with radiation therapy followed by surgery and postoperative 5-FU, leucovorin, oxaliplatin (FOLFOX) and bevacizumab for locally advanced rectal cancer.. Fifty-seven patients with resectable T3/T4 rectal adenocarcinoma were enrolled. Preoperative treatment was capecitabine (825 mg/m(2) twice daily from Monday to Friday), oxaliplatin (50 mg/m(2) weekly), bevacizumab (5 mg/kg on days 1, 15, 29), and radiation therapy (50.4 Gy). Surgery was performed by 6 weeks after neoadjuvant therapy. Beginning 8 to 12 weeks after surgery, patients received FOLFOX plus bevacizumab (5 mg/kg) every 2 weeks for 12 cycles.. Fifty-four of 57 enrolled patients were eligible. Forty-nine (91%) patients completed preoperative therapy and underwent surgery. Nine patients (17%; 90% confidence interval, 9%-27%) achieved pathologic complete response. Thirty-two patients (59%) experienced pathologic tumor downstaging, and 53% and 15% of patients experienced worst grade 3 and grade 4 acute toxicity, respectively. Forty-seven percent of patients who underwent surgery experienced a surgical complication.. The primary endpoint of a 30% pathologic complete response rate was not reached; however, the majority of patients experienced pathologic downstaging with this regimen. Increased wound-healing delays and complications may have been related to the addition of bevacizumab, oxaliplatin, or both. Continued observation of these patients will establish the long-term morbidity and efficacy of this combined modality approach.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Capecitabine; Chemoradiotherapy; Deoxycytidine; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaliplatin; Postoperative Period; Radiotherapy Dosage; Rectal Neoplasms; Survival Analysis

To evaluate the feasibility and pathologic complete response rate of induction bevacizumab + modified infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) 6 regimen followed by concurrent bevacizumab, oxaliplatin, continuous infusion 5-fluorouracil (5-FU), and radiation for patients with rectal cancer.. Eligible patients received 1 month of induction bevacizumab and mFOLFOX6. Patients then received 50.4 Gy of radiation and concurrent bevacizumab (5 mg/kg on Days 1, 15, and 29), oxaliplatin (50 mg/m(2)/week for 6 weeks), and continuous infusion 5-FU (200 mg/m(2)/day). Because of gastrointestinal toxicity, the oxaliplatin dose was reduced to 40 mg/m(2)/week. Resection was performed 4-8 weeks after the completion of chemoradiation.. The trial was terminated early because of toxicity after 26 eligible patients were treated. Only 1 patient had significant toxicity (arrhythmia) during induction treatment and was removed from the study. During chemoradiation, Grade 3/4 toxicity was experienced by 19 of 25 patients (76%). The most common Grade 3/4 toxicities were diarrhea, neutropenia, and pain. Five of 25 patients (20%) had a complete pathologic response. Nine of 25 patients (36%) developed postoperative complications including infection (n = 4), delayed healing (n = 3), leak/abscess (n = 2), sterile fluid collection (n = 2), ischemic colonic reservoir (n = 1), and fistula (n = 1).. Concurrent oxaliplatin, bevacizumab, continuous infusion 5-FU, and radiation causes significant gastrointestinal toxicity. The pathologic complete response rate of this regimen was similar to other fluorouracil chemoradiation regimens. The high incidence of postoperative wound complications is concerning and consistent with other reports utilizing bevacizumab with chemoradiation before major surgical resections.

Topics: Adenocarcinoma; Adult; Aged; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Diarrhea; Drug Administration Schedule; Early Termination of Clinical Trials; Feasibility Studies; Female; Fluorouracil; Humans; Induction Chemotherapy; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Pain; Postoperative Complications; Prospective Studies; Radiotherapy Dosage; Rectal Neoplasms

To evaluate the rate of pathologic complete response (pCR) and the toxicity of two neoadjuvant chemoradiotherapy (chemoRT) regimens for Stage T3-T4 rectal cancer in a randomized Phase II study.. Patients with Stage T3 or T4 rectal cancer of <12 cm from the anal verge were randomized to preoperative RT (50.4 Gy in 1.8-Gy fractions) with concurrent capecitabine (1,200 mg/m(2)/d Mondays through Friday) and irinotecan (50 mg/m(2) weekly in four doses) (Arm 1) or concurrent capecitabine (1,650 mg/m(2)/d Monday through Friday) and oxaliplatin (50 mg/m(2) weekly in five doses) (Arm 2). Surgery was performed 4-8 weeks after chemoRT, and adjuvant chemotherapy 4-6 weeks after surgery. The primary endpoint was the pCR rate, requiring 48 evaluable patients per arm.. A total of 146 patients were enrolled. The protocol chemotherapy was modified because of excessive gastrointestinal toxicity after treatment of 35 patients; 96 were assessed for the primary endpoint-the final regimen described above. The patient characteristics were similar for both arms. After chemoRT, the rate of tumor downstaging was 52% and 60% and the rate of nodal downstaging (excluding N0 patients) was 46% and 40%, for Arms 1 and 2, respectively. The pCR rate for Arm 1 was 10% and for Arm 2 was 21%. For Arm 1 and 2, the preoperative chemoRT rate of Grade 3-4 hematologic toxicity was 9% and 4% and the rate of Grade 3-4 nonhematologic toxicity was 26% and 27%, respectively.. Preoperative chemoRT with capecitabine plus oxaliplatin for distal rectal cancer has significant clinical activity (10 of 48 pCRs) and acceptable toxicity. This regimen is currently being evaluated in a Phase III randomized trial (National Surgical Adjuvant Breast and Bowel Project R04).

Topics: Adult; Aged; Algorithms; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Capecitabine; Chemoradiotherapy; Chemotherapy, Adjuvant; Deoxycytidine; Drug Administration Schedule; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Radiotherapy Dosage; Rectal Neoplasms

To achieve T-downstaging and better resectability in locally advanced rectal cancer, neoadjuvant radiochemotherapy (RCT) has become the current standard of treatment. A variety of schemes have been used. This study investigates which scheme had the best effect on these parameters.. Our institution is a referral center for locally advanced rectal cancer. Different neoadjuvant radiochemotherapy regimens were administered: long course radiotherapy (RTH), 5-FU and leucovorin (5FUBolus), a combination of capecitabine and oxaliplatin (CORE), and capecitabine only (CAP). Selection of patients for 1 of the regimens was based on hospital policy rather than patient or tumor characteristics.. The data of 504 consecutive patients (n = 181 T3+, n = 323 T4) without metastatic disease (cM0) who underwent surgery for advanced rectal carcinoma between 1994 and 2010 were reviewed. The RTH, 5FUBolus, CORE, and CAP scheme were administered to 106, 137, 155, and 106 patients, respectively. Odds ratios for downstaging were less effective for RTH, 5FUBolus, and CAP (0.31, 0.44, and 0.31; P < .0001) when compared with the CORE scheme. Odds ratios for a R1 resection (3.74, 1.94, 1.14; P = .003) or CRM+ resection (3.78, 2.73, 1.34; P = .001) were also in favor of the CORE. Hazard ratios for CSS were significantly better for the CORE scheme.. Downstaging with neoadjuvant treatment results in an increased number of radical resections. In our study, the combination of capecitabine and oxaliplatin appears to be the most effective regimen for locally advanced rectal cancer tumors. However, longer follow-up will be necessary to confirm this conclusion.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemoradiotherapy; Deoxycytidine; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Preoperative Care; Prospective Studies; Rectal Neoplasms; Survival Rate; Treatment Outcome

We wanted to evaluate the efficacy, defined as 2-year disease-free survival (DFS), and safety of bevacizumab/chemoradiation in preoperative and adjuvant settings for patients with stage II/III rectal cancer.. Eligible patients had stage II/III rectal adenocarcinoma, Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1, and adequate organ function, and received preoperative (cohort A) or adjuvant (cohort B) treatment at physician discretion. Patients received 5-fluorouracil (5-FU) as an intravenous infusion (IVCI) 225 mg/m(2)/d on days 1-42, bevacizumab 5 mg/kg intravenously (I.V.) on days 1 and 15 (cohort A), or every 2 weeks (cohort B), with radiation therapy to 50.4 Gy. After surgery (cohort A) or chemoradiation (cohort B), FOLFOX6 (5-fluorouracil, leucovorin, oxaliplatin) and bevacizumab were administered for 4 months and then bevacizumab was given alone for up to 1 year.. Sixty-six patients (cohort A = 35; cohort B = 31) were enrolled from August 2006-April 2009: median age was 57 years; male patients, 62%; ECOG PS 0, 75%; stage II/III, 31%/69%. In cohort A, the complete pathologic response (pCR) rate was 29% (11% microscopic residual disease, 49% gross disease). Four patients did not undergo surgery (toxicity, 2 patients; progressive disease, 1 patient; patient decision, 1 patient). One- and 2-year DFS for cohorts A/B were 85%/not reached and 97%/89%, respectively (median survival not reached for either cohort). Frequent grade 3/4 toxicity included diarrhea (A cohort, 14%; B cohort, 29%), neutropenia (A cohort, 14%, B cohort, 23%), mucositis (A cohort, 23%, B cohort, 0%), and fatigue (A cohort, 6%, B cohort, 10%). Other serious toxicity included bowel perforation and pelvic infection (cohort A, 1 patient each), bowel perforation (2 patients), anal wound dehiscence (1 patient), perianal infection (2 patients), and rectovaginal fistula (1 patient) (cohort B), without treatment-related death in either cohort.. Bevacizumab can be added to standard preoperative and adjuvant chemoradiation in most patients with expected and manageable toxicity and may increase treatment efficacy.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Chemoradiotherapy; Chemotherapy, Adjuvant; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Preoperative Care; Rectal Neoplasms; Survival Rate; Treatment Outcome

The aim of this study was to compare the downstaging achieved after long-course chemoradiotherapy (chRT) and short-term radiotherapy (sRT) followed by delayed surgery.. A randomized controlled trial was carried out. Eighty-three patients with resectable stage II and III rectal adenocarcinoma were randomized to receive long-course chemoradiotherapy (46) and short-term radiotherapy (5×5 Gy) (37). Surgery was performed 6 weeks after preoperative treatment in both groups.. The R0 resection rate was 91.3% in the chRT and 86.5% in the sRT group (P=0.734). Sphincter preservation rates were 69.6%vs 70.3% (P=0.342) and postoperative complication rates were 26.1%vs 40.5% (P=0.221). There were more patients with early pT stage [pT0 (complete pathological response) pT1] in the chRT group [21.8%vs 2.7% (P=0.03)] and more patients with pT3 disease in the sRT group [75.7%vs 52.2% (P=0.036)]. There were no differences in pN stage and lymphatic or vascular invasion in either group. Pathological downstaging (stage 0 and I) was observed in eight (21.6%) patients in the sRT group and in 18 (39.1%) in the chRT group (P=0.07). Tumours were smaller after preoperative ChRT (2.5 cm vs 3.3 cm; P=0.04).. Long-course preoperative chemoradiation resulted in greater statistically significant tumour downsizing and downstaging compared with short-term radiation, but there was no difference in the R0 resection rates. Similar postoperative morbidity was observed in each group.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Chemoradiotherapy, Adjuvant; Drug Administration Schedule; Endosonography; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Postoperative Complications; Preoperative Care; Radiotherapy, Adjuvant; Rectal Neoplasms; Rectum; Single-Blind Method; Treatment Outcome; Vitamin B Complex

Induction chemotherapy has been suggested to impact on preoperative chemoradiation efficacy in locally advanced rectal cancer (LARC). To evaluate in LARC patients, the feasibility and efficacy of a short intense course of induction oxaliplatin before preoperative chemoradiotherapy (CRT).. Patients with T2-T4/N+ rectal adenocarcinoma were randomly assigned to arm A-preoperative CRT with 5-fluorouracil (5-FU) continuous infusion followed by surgery-or arm B-induction oxaliplatin, folinic acid and 5-FU followed by CRT and surgery. The primary end point was the rate of ypT0-1N0 stage achievement.. Fifty seven patients were randomly assigned (arm A/B: 29/28) and evaluated for planned interim analysis. On an intention-to-treat basis, the ypT0-1N0 rate for arms A and B were 34.5% (95% CI: 17.2% to 51.8%) and 32.1% (95% CI: 14.8% to 49.4%), respectively, and the study therefore was closed prematurely for futility. There were no statistically significant differences in other end points including pathological complete response, tumor regression and sphincter preservation. Completion of the preoperative CRT sequence was similar in both groups. Grade 3/4 toxicity was significantly higher in arm B.. Short intense induction oxaliplatin is feasible in LARC patients without compromising the preoperative CRT completion, although the current analysis does not indicate increased locoregional impact on standard therapy.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Chemotherapy, Adjuvant; Digestive System Surgical Procedures; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Radiotherapy Dosage; Rectal Neoplasms; Treatment Outcome; Tumor Burden; Young Adult

Consensus is that patients with locally advanced rectal cancer (LARC) should receive long-term chemoradiotherapy (CRT) before surgery. With the intent to offer the patients intensified concomitant chemotherapy (CT) to improve outcome and to assess tolerability and toxicity of oxaliplatin (Ox) a phase I trial of high dose pelvic radiotherapy (RT), fixed dose of oral UFT/l-leucovorin and increasing doses of weekly Ox were performed.. Pelvic RT with 48.6 Gy/27 fractions was given to the primary tumour and the regional lymph nodes and a concurrent boost of 5.4 Gy/27 fractions with a final boost of 6 Gy/3 fractions was given to the gross tumour volume (GTV) (60 Gy/30 fractions). Concurrent with RT patients received a daily dose of UFT 300 mg/m(2) plus fixed dose l-leucovorin 22.5 mg 5/7 days and increasing weekly doses of Ox with 10 mg/m(2)/week from a start dose of 30 mg/m(2)/week to a maximum of 60 mg/m(2)/week. In addition, before and after CRT the patients received one course of TEGAFOX (UFT 300 mg/m(2) with l/leucovorin 22.5 mg Days 1-14 and Ox 130 mg/m(2) given on Day 1). Surgery was planned at least six weeks after the completion of the CRT.. From May 2005 to March 2009, 18 patients with LARC (16 primary, two recurrent) were included in this phase I trial. Toxicity was low with only 5-17% grade 3-4 toxicity. Fifteen patients (83%) were operated (14 R0 resection and 1 R1 resection) after completion of CRT. Five (33%) patients had a pathological complete response (ypCR). When ypCR was combined with yp few residual cells, the rate was 60%. Thirteen patients are still alive December 2011.. Preoperative high-dose RT and concomitant UFT with increasing doses of Ox up to 60 mg/m(2)/week was feasible with low toxicity, high ypCR rates and promising OS in patients with non-resectable LARC.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Feasibility Studies; Female; Fluorouracil; Follow-Up Studies; Gamma Rays; Humans; Leucovorin; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Radiotherapy Dosage; Rectal Neoplasms; Survival Rate; Tegafur; Treatment Outcome; Uracil

To perform a prospective phase II study to investigate the efficacy and safety of preoperative pelvic radiation therapy and concomitant small-field boost irradiation with 5-fluorouracil and leucovorin for 5 weeks in locally advanced rectal cancer patients.. Sixty-nine patients with locally advanced, nonmetastatic, mid-to-lower rectal cancer were prospectively enrolled. They had received preoperative chemoradiation therapy and total mesorectal excision. Pelvic radiation therapy of 43.2 Gy in 24 fractions plus concomitant boost radiation therapy of 7.2 Gy in 12 fractions was delivered to the pelvis and tumor bed for 5 weeks. Two cycles of 5-fluorouracil and leucovorin were administered for 3 days in the first and fifth week of radiation therapy. The pathologic response, survival outcome, and treatment toxicity were evaluated for the study endpoints.. Of 69 patients, 8 (11.6%) had a pathologically complete response. Downstaging rates were 40.5% for T classification and 68.1% for N classification. At the median follow-up of 69 months, 36 patients have been followed up for more than 5 years. The 5-year disease-free survival (DFS) and overall survival rates were 66.0% and 75.3%, respectively. Higher pathologic T (P=.045) and N (P=.032) classification were significant adverse prognostic factors for DFS, and high-grade histology was an adverse prognostic factor for both DFS (P=.025) and overall survival (P=.031) on the multivariate analysis. Fifteen patients (21.7%) experienced grade 3 or 4 acute toxicity, and 7 patients (10.1%) had long-term toxicity.. Preoperative pelvic radiation therapy with concomitant boost irradiation with 5-fluorouracil and leucovorin for 5 weeks showed acceptable acute and long-term toxicities. However, the benefit of concomitant small-field boost irradiation for 5 weeks in rectal cancer patients was not demonstrated beyond conventional irradiation for 6 weeks in terms of tumor response and survival.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Chemoradiotherapy; Disease-Free Survival; Dose Fractionation, Radiation; Drug Administration Schedule; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Pelvis; Preoperative Care; Prospective Studies; Radiotherapy, Adjuvant; Rectal Neoplasms; Remission Induction; Survival Rate

The ACCORD 12 trial investigated the value of two different preoperative chemoradiotherapy (CT-RT) regimens in T3-4 Nx M0 resectable rectal cancer. Clinical results are reported after follow-up of 3 years.. Between November 2005 and July 2008, a total of 598 patients were randomly assigned to preoperative CT-RT with CAP45 (45-Gy RT for 5 weeks with concurrent capecitabine) or CAPOX50 (50-Gy RT for 5 weeks with concurrent capecitabine and oxaliplatin). Total mesorectal excision was planned 6 weeks after CT-RT. The primary end point was sterilization of the operative specimen, which was achieved in 13.9% versus 19.2% of patients, respectively (P = .09). Clinical results were analyzed for all randomly assigned patients according to the intention-to-treat principle.. At 3 years, there was no significant difference between CAP45 and CAPOX50 (cumulative incidence of local recurrence, 6.1% v 4.4%; overall survival, 87.6% v 88.3%; disease-free survival, 67.9% v 72.7%). Grade 3 to 4 toxicity was reported in four patients in the CAP45 group and in two patients in the CAPOX50 group. Bowel continence, erectile dysfunction, and social life disturbance were not different between groups. In multivariate analysis, the sterilization rate (Dworak score) of the operative specimen was the main significant prognostic factor (hazard ratio, 0.32; 95% CI, 0.21 to 0.50).. At 3 years, no significant difference in clinical outcome was achieved with the intensified CAPOX regimen. When compared with other recent randomized trials, these results indicate that concurrent administration of oxaliplatin and RT is not recommended.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemoradiotherapy, Adjuvant; Deoxycytidine; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Radiotherapy Dosage; Rectal Neoplasms; Treatment Outcome

In a randomized trial the effect of short-term preoperative radiotherapy and postoperative chemotherapy was studied in patients undergoing total mesorectal excision (TME) for clinically resectable rectal cancer. The primary endpoint was overall survival. The secondary endpoints published herein were the incidence of postoperative complications and adverse events with perioperative adjuvant therapy.. In 1995-2002, 278 eligible patients with stage II and stage III rectal cancer were randomly assigned to TME alone (surgery group) or to preoperative 25 Gy radio-therapy in 5 fractions and postoperative 5-fluorouracil and leucovorin chemotherapy in addition (RT+CT group).. Anastomotic leakage rate did not significantly differ between the surgery and the RT + CT group, 20.6% vs. 27.4%. Postoperative infections (15.5 vs. 26.2%, p = 0.037) and perineal wound dehiscence (15.9 vs. 38.5%, p = 0.045) were more common after radiotherapy. Grade 3-5 adverse events were uncommon with preoperative radiotherapy (one, 0.7% with reversible lumbar plexopathy) and postoperative chemotherapy (hematologic in 10.8%, with one septic death, and gastrointestinal in 4.8%).. Perioperative adjuvant therapy was generally well tolerated and did not lead to an increase in serious surgical complications. Wound infections and perineal wound dehiscence were more common in irradiated patients.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Dose Fractionation, Radiation; Female; Finland; Fluorouracil; Follow-Up Studies; Humans; Incidence; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Postoperative Complications; Prospective Studies; Radiotherapy, Adjuvant; Rectal Neoplasms; Rectum; Treatment Outcome; Young Adult

A regimen consisting of 5-fluorouracil/leucovorin plus oxaliplatin (FOLFOX-6) is widely used in France in the first-line treatment of metastatic colorectal cancer (MCRC). The aim of our study was to demonstrate the non-inferiority of capecitabine plus oxaliplatin (XELOX) versus FOLFOX-6 for this indication. Patients were randomly assigned to receive XELOX or FOLFOX-6 for 6 months. The primary endpoint was overall response rate (ORR) in the per-protocol (PP) population; however, progression-free and overall survival (OS), time to response and response duration were also assessed. A total of 306 patients were enrolled (XELOX n = 156; FOLFOX-6 n = 150). ORR was 42 and 46% with XELOX and FOLFOX-6, respectively, in the PP population. The difference between groups was 4.7%; the upper limit of the unilateral 95% confidence interval (14.4%) was below the non-inferiority margin of 15%. In the intent-to-treat population, median progression-free survival was 8.8 months with XELOX and 9.3 months with FOLFOX-6, and median OS was 19.9 and 20.5 months, respectively. XELOX patients had significantly more grade 3/4 thrombocytopenia (12% vs. 5%) and diarrhoea (14% vs. 7%), but significantly less grade 3/4 neutropenia (5% vs. 47%), febrile neutropenia (0% vs. 6%) and neuropathy (11% vs. 26%) than FOLFOX-6 patients. We conclude that XELOX is non-inferior in terms of efficacy to FOLFOX-6 in the first-line treatment of MCRC, but has a different toxicity profile.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Colonic Neoplasms; Colorectal Neoplasms; Deoxycytidine; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms; Treatment Outcome; Young Adult

This study aimed to evaluate the technical feasibility of laparoscopic total mesorectal excision (TME) for the treatment of low rectal cancer after concurrent chemoradiation therapy (CCRT) with bevacizumab and FOLFOX.. Patients with clinical T3, T4, or N1-2 rectal cancer were subjected to a preoperative CCRT protocol with FOLFOX and bevacizumab (5 mg/kg) biweekly for 6 cycles followed by a standardized laparoscopic TME procedure, as detailed in the attached video.. The treatment protocol was completed by 28 patients. Scrutiny of the video indicated that the dissection plane was a little blurred due to preoperative CCRT, but this did not significantly increase the technical difficulties. Laparoscopic TME was efficiently performed with acceptable operation time (214.4 ± 44.4 min). However, the median blood loss (420 ml; range, 120-1,200 ml) in this series was significantly greater than in the historic series without bevacizumab therapy. Bevacizumab seems not to increase the severity of FOLFOX-related liver steatosis and sinusoidal dilation. One operative mortality (3.6%) occurred. Six patients (21.4%) presented with postoperative complications including upper gastrointestinal bleeding, deep vein thrombosis, pelvic abscess, wound infection, enterocutaneous fistula, and perineal fistula. The patients presented with mild postoperative pain and had a quick convalescence. The addition of bevacizumab to FOLFOX achieved a superior pathologic response for 78.3% of the patients, whose residual tumor cells were very few (< 10% microscopic field).. Based on the controllable surgical complications and minimal invasiveness in the current patient series, laparoscopic TME is shown to be technically feasible and can be recommended for patients with advanced lower rectal cancer requiring preoperative CCRT using bevacizumab as the additional therapeutic agent.

Topics: Adenocarcinoma; Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Combined Modality Therapy; Disease Progression; Dose Fractionation, Radiation; Feasibility Studies; Female; Fluorouracil; Follow-Up Studies; Humans; Laparoscopy; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaliplatin; Postoperative Complications; Rectal Neoplasms; Rectum; Treatment Outcome

To determine the optimal sequence of postoperative adjuvant chemotherapy and radiotherapy in patients with Stage II or III rectal cancer.. A total of 308 patients were randomized to early (n = 155) or late (n = 153) radiotherapy (RT). Treatment included eight cycles of chemotherapy, consisting of fluorouracil 375 mg/m(2)/day and leucovorin 20 mg/m(2)/day, at 4-week intervals, and pelvic radiotherapy of 45 Gy in 25 fractions. Radiotherapy started on Day 1 of the first chemotherapy cycle in the early RT arm and on Day 1 of the third chemotherapy cycle in the late RT arm.. At a median follow-up of 121 months for surviving patients, disease-free survival (DFS) at 10 years was not statistically significantly different between the early and late RT arms (71% vs. 63%; p = 0.162). A total of 36 patients (26.7%) in the early RT arm and 49 (35.3%) in the late RT arm experienced recurrence (p = 0.151). Overall survival did not differ significantly between the two treatment groups. However, in patients who underwent abdominoperineal resection, the DFS rate at 10 years was significantly greater in the early RT arm than in the late RT arm (63% vs. 40%; p = 0.043).. After the long-term follow-up duration, this study failed to show a statistically significant DFS advantage for early radiotherapy with concurrent chemotherapy after resection of Stage II and III rectal cancer. Our results, however, suggest that if neoadjuvant chemoradiation is not given before surgery, then early postoperative chemoradiation should be considered for patients requiring an abdominoperineal resection.

Topics: Antineoplastic Agents; Chemoradiotherapy; Chemotherapy, Adjuvant; Disease-Free Survival; Dose Fractionation, Radiation; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Rectal Neoplasms; Time Factors

Preoperative chemoradiotherapy (CRT) is superior to radiotherapy (RT) in locally advanced rectal cancer, but the survival gain is limited. Late toxicity is, therefore, important. The aim was to compare late bowel, urinary, and sexual functions after CRT or RT.. Patients (N = 207) with nonresectable rectal cancer were randomized to preoperative CRT or RT (2 Gy × 25 ± 5-fluorouracil/leucovorin). Extended surgery was often required. Self-reported late toxicity was scored according to the LENT SOMA criteria in a structured telephone interview and with questionnaires European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30), International Index of Erectile Function (IIEF), and sexual function-vaginal changes questionnaire (SVQ).. Of the 105 patients alive in Norway and Sweden after 4 to 12 years of follow-up, 78 (74%) responded. More patients in the CRT group had received a stoma (73% vs. 52%, p = 0.09). Most patients without a stoma (7 of 12 in CRT group and 9 of 16 in RT group) had incontinence for liquid stools or gas. No stoma and good anal function were seen in 5 patients (11%) in the CRT group and in 11 (30%) in the RT group (p = 0.046). Of 44 patients in the CRT group, 12 (28%) had had bowel obstruction compared with 5 of 33 (15%) in the RT group (p = 0.27). One-quarter of the patients reported urinary incontinence. The majority of men had severe erectile dysfunction. Few women reported sexual activity during the previous month. However, the majority did not have concerns about their sex life.. Fecal incontinence and erectile dysfunction are frequent after combined treatment for locally advanced rectal cancer. There was a clear tendency for the problems to be more common after CRT than after RT.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Chemoradiotherapy; Diagnostic Self Evaluation; Fecal Incontinence; Female; Fluorouracil; Follow-Up Studies; Humans; Intestinal Obstruction; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Penile Erection; Preoperative Care; Quality of Life; Radiotherapy; Rectal Neoplasms; Sex Factors; Sexuality; Surgical Stomas; Surveys and Questionnaires; Time Factors; Tumor Burden; Urinary Incontinence; Vagina

To determine whether irinotecan plus oxaliplatin (mIROX) is superior to irinotecan plus infusional 5-fluorouracil, leucovorin (FUFIRI) as first-line therapy of patients with metastatic colorectal cancer (mCRC).. A phase III, randomised, open-label multicentre study compared standard treatment with FUFIRI (irinotecan 80 mg/m(2), 5-fluorouracil 2000 mg/m(2), folinic acid 500 mg/m(2) weekly times 6) to mIROX using an identical schedule of irinotecan plus oxaliplatin 85 mg/m(2) applied on days 1, 15 and 29 of a 7-week cycle. The primary end-point was progression-free survival (PFS).. A total of 479 eligible patients were randomly assigned. Progression-free survival was 7.2 months in the mIROX arm and 8.2 months in the FUFIRI arm [hazard ratio=1.14; 95% confidence interval (CI) 0.94-1.37; P=0.178]. Comparable results were also obtained for overall survival time with 19 months in the mIROX-arm and 22 months in the FUFIRI-arm (hazard ratio=1.08, P=0.276). Both regimens induced an identical objective response rate (ORR) of 41%, but disease control rate (ORR plus stable disease) was significantly greater in the FUFIRI group (81% versus 68%, P=0.001). Most frequent grades 1-4 side-effects of mIROX and FUFIRI treatment were nausea (80% versus 73%) and delayed diarrhoea (79% versus 68%). Grades 3-4 toxicities were generally below 10%, except for diarrhoea which was more frequent in the mIROX-arm compared to the FUFIRI-arm (19% versus 30%, P=0.006). mIROX failed to show superior activity compared to high-dose 5-FU/folinic acid plus irinotecan. Due to better tolerability the combination of high-dose 5-FU/folinic acid and irinotecan remains a standard of care in first-line treatment of metastatic colorectal cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Disease-Free Survival; Female; Fluorouracil; Humans; Infusions, Intravenous; Irinotecan; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms; Young Adult

The aim of this study was to evaluate the clinical implications of pathologic complete response (pCR) (i.e., T0N0M0) after neoadjuvant chemoradiation and radical surgery in patients with locally advanced rectal cancer.. A single-center, prospectively maintained colorectal cancer database was queried for patients with primary cII and cIII rectal cancer staged by CT and ERUS/MRI undergoing long-course neoadjuvant chemoradiation followed by proctectomy with curative intent between 1997 and 2007. Patients were stratified into pCR and no-pCR groups and compared with respect to demographics, tumor and treatment characteristics, and oncologic outcomes. Outcomes evaluated were 5-year overall survival, disease-free survival, disease-specific mortality, local recurrence, and distant recurrence.. The query returned 238 patients (73% male), with a median age of 57 years and median follow-up of 54 months. Of these, 58 patients achieved pCR. Patients with pCR vs no-pCR were statistically comparable with respect to demographics, chemoradiation regimens, tumor distance from anal verge, clinical stage, surgical procedures performed, and follow-up time. No patient with pCR had local recurrence. Overall survival and distant recurrence were also significantly improved for patients achieving pCR.. Achievement of pCR after neoadjuvant chemoradiation is associated with greatly improved cancer outcomes in locally advanced rectal cancer. Future studies should evaluate the relationship between increases in pCR rates and improvements in cancer outcomes in this population.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Prospective Studies; Rectal Neoplasms; Remission Induction; Survival Rate; Treatment Outcome

Considerable variation in intravenous 5-fluorouracil (5-FU) metabolism can occur due to the wide range of dihydropyrimidine dehydrogenase (DPD) enzyme activity, which can affect both tolerability and efficacy. The oral fluoropyrimidine tegafur-uracil (UFT) is an effective, well-tolerated and convenient alternative to intravenous 5-FU. We undertook this study in patients with locally advanced rectal cancer to evaluate the efficacy and tolerability of UFT with leucovorin (LV) and preoperative radiotherapy and to evaluate the utility and limitations of multicenter staging using pre- and post-chemoradiotherapy ultrasound. We also performed a validated pretherapy assessment of DPD activity and assessed its potential influence on the tolerability of UFT treatment.. This phase II study assessed preoperative UFT with LV and radiotherapy in 85 patients with locally advanced T3 rectal cancer. Patients with potentially resectable tumors received UFT (300 mg/m/2/day), LV (75 mg/day), and pelvic radiotherapy (1.8 Gy/day, 45 Gy total) 5 days/week for 5 weeks then surgery 4-6 weeks later. The primary endpoints included tumor downstaging and the pathologic complete response (pCR) rate.. Most adverse events were mild to moderate in nature. Preoperative grade 3/4 adverse events included diarrhea (n = 18, 21%) and nausea/vomiting (n = 5, 6%). Two patients heterozygous for dihydropyrimidine dehydrogenase gene (DPYD) experienced early grade 4 neutropenia (variant IVS14+1G > A) and diarrhea (variant 2846A > T). Pretreatment ultrasound TNM staging was compared with postchemoradiotherapy pathology TN staging and a significant shift towards earlier TNM stages was observed (p < 0.001). The overall downstaging rate was 42% for primary tumors and 44% for lymph nodes. The pCR rate was 8%. The sensitivity and specificity of ultrasound for staging was poor. Anal sphincter function was preserved in 55 patients (65%). Overall and recurrence-free survival at 3 years was 86.1% and 66.7%, respectively. Adjuvant chemotherapy was administered to 36 node-positive patients (mean duration 118 days).. Preoperative chemoradiotherapy using UFT with LV plus radiotherapy was well tolerated and effective and represents a convenient alternative to 5-FU-based chemoradiotherapy for the treatment of resectable rectal cancer. Pretreatment detection of DPD deficiency should be performed to avoid severe adverse events.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Female; Humans; Leucovorin; Male; Middle Aged; Preoperative Period; Radiotherapy, Adjuvant; Rectal Neoplasms; Tegafur; Uracil; Young Adult

To identify a biomarker profile associated with tumor response to chemoradiation (CRT) in locally advanced rectal cancer.. Rectal cancer response to neoadjuvant CRT is variable. Whereas some patients have a minimal response, others achieve a pathologic complete response (pCR) and have no viable cancer cells in their surgical specimens. Identifying biomarkers of response will help select patients more likely to benefit from CRT.. This study includes 132 patients with locally advanced rectal cancer treated with neoadjuvant CRT followed by surgery. Tumor DNA from pretreatment tumor biopsies and control DNA from paired normal surgical specimens was screened for mutations and polymorphisms in 23 genes. Genetic biomarkers were correlated with tumor response to CRT (pCR vs non-pCR), and the association of single or combined biomarkers with tumor response was determined.. Thirty-three of 132 (25%) patients achieved a pCR and 99 (75%) patients had non-pCR. Three individual markers were associated with non-pCR; v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog mutation (P = 0.0145), cyclin D1 G870A (AA) polymorphism (P = 0.0138), and methylenetetrahydrofolate reductase (NAD(P)H) C677T (TT) polymorphism (P = 0.0120). Analysis of biomarker combinations revealed that none of the 27 patients with both tumor protein p53 (p53) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog mutations had a pCR. Further, in patients with both p53 and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog mutations or the cyclin D1 G870A (AA) polymorphism or the methylenetetrahydrofolate reductase (NAD(P)H) C677T (TT) polymorphism (n = 52) the association with non-pCR was further strengthened; 51 of 52 (98%) of patients were non-pCR. These biomarker combinations had a validity of more than 70% and a positive predictive value of 97% to 100%, predicting that patients harboring these mutation/polymorphism profiles will not achieve a pCR.. A specific biomarker profile is strongly associated with non-pCR to CRT and could be used to select optimal oncologic therapy in rectal cancer patients. ClinicalTrials.org Identifier: NCT00335816.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Chemotherapy, Adjuvant; Cyclin D1; Drug Resistance, Neoplasm; Female; Fluorouracil; Genes, p53; Genotype; Humans; Leucovorin; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Mutation; Neoadjuvant Therapy; Neoplasm Invasiveness; Neoplasm Staging; Organoplatinum Compounds; Polymorphism, Genetic; Predictive Value of Tests; Prognosis; Prospective Studies; Proto-Oncogene Proteins; Proto-Oncogene Proteins p21(ras); Radiotherapy Dosage; Radiotherapy, Adjuvant; ras Proteins; Rectal Neoplasms; Reproducibility of Results; Sensitivity and Specificity; Treatment Outcome; United States

For rectal cancer patients without nodal metastases the identification of unfavourable factors can be helpful for the better selection for adjuvant therapy and multimodality treatment. The aim of this study was to evaluate the impact of clinico-histological parameters on prognosis in node-negative rectal cancer patients. One hundred and thirty-nine consecutive node negative rectal cancer patients with complete five-year follow-up were studied prospectively. All of them underwent curative anterior resection with total mesorectal excision technique. Seventy-eight patients with tumour penetration beyond the bowel wall received neo-adjuvant short-course radiation (25 Gy) followed by surgery within 1 week and postoperative chemotherapy with 5-fluorouracil and folinic acid in six cycles or adjuvant radiochemotherapy: irradiation (50.4 Gy) combined with chemotherapy (as above). Cancer-specific survival was calculated according to the Kaplan-Meier method. Variables significant in univariate analysis by log-rank test (P < 0.05) entered the Cox proportional hazard model. Survival was decreased for males, older patients (>60 years) with extraperitoneal, poorly differentiated cancers, tumours with mucinous histology and with the absence of lymphocytic infiltration but with the lack of statistical importance. Prognosis was significantly improved for patients with T2 tumours versus T3 (P < 0.01) and with cancers with expanding growth comparing to diffusely infiltrating ones (P < 0.01). In multivariate analysis these parameters significantly and independently influenced survival (P < 0.01 and P < 0.05, respectively). Diffusely infiltrating growth of tumour can reflect the more aggressive cancer behaviour and unfavourable course of disease despite the optimised local control. Apart from the extent of tumour penetration the type of invasive margin can be an additional parameter helpful for the optimal treatment planning and better patient selection for postoperative chemotherapy.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Digestive System Surgical Procedures; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Prognosis; Proportional Hazards Models; Radiotherapy; Rectal Neoplasms

The aim of this retrospective case-matching study was to compare the treatment outcomes and acute toxicity of preoperative radiotherapy (RT) with capecitabine vs. preoperative RT with intermittent 5-fluorouracil (5-FU) infusion, leucovorin, and mitomycin C in rectal cancer.. We matched 34 patients who were treated with preoperative concurrent capecitabine and 50 Gy of RT by their clinical T stage (T3 or T4) and the tumor location (7 cm from the anal verge) with another 68 patients who were treated with preoperative intermittent 5-FU infusion, leucovorin, mitomycin C, and 50 Gy of RT for a comparison of the pathologic tumor response, local control, distant failure, and survival rates.. The pathologic complete response rate was 21% with capecitabine and 18% with 5-FU and leucovorin (p = 0.72). The rate of T downstaging after chemoradiation was 59% for both groups. The rate of sphincter-sparing resection was 38% after capecitabine plus RT and 43% after 5-FU plus RT (p = 0.67). At 3 years, there was no significant difference in the local control rate (93% for capecitabine and 92% for 5-FU and leucovorin), relapse-free rate (74% for capecitabine and 73% for 5-FU and leucovorin), or disease-specific survival rate (86% for capecitabine and 77% for 5-FU and leucovorin). The acute toxicity profile was comparable, with little Grade 3 and 4 toxicity.. When administered with concurrent preoperative RT, both capecitabine and intermittent 5-FU infusion with leucovorin modulation provided comparable pathologic tumor response, local control, relapse-free survival, and disease-specific survival rates in rectal cancer.

Topics: Administration, Oral; Adult; Aged; Antimetabolites, Antineoplastic; Capecitabine; Chemotherapy, Adjuvant; Deoxycytidine; Female; Fluorouracil; Humans; Leucovorin; Male; Matched-Pair Analysis; Middle Aged; Mitomycin; Neoadjuvant Therapy; Preoperative Care; Radiotherapy Dosage; Rectal Neoplasms; Remission Induction; Retrospective Studies; Survival Rate; Therapeutic Equivalency

The aim of this study was to evaluate the usefulness of neoadjuvant systemic chemotherapy using irinotecan, 5-FU, and leucovorin (LV) for the treatment of locally advanced rectal cancer, which was a powerful ploychemotherapy in those days in Japan.. Between 2001 and 2004, 26 patients with T3 or T4 and N0-2 non-metastatic resectable rectal cancer were selectively enrolled in this study. Neoadjuvant chemotherapy consisted of two cycles of irinotecan (80 mg/m²), 5-FU (500 mg/m²), and LV (250 mg/m²) on days 1, 8, and 15 for 4 weeks. Surgical resection was performed in all the patients 2-4 weeks after the completion of chemotherapy.. Overall down-staging was observed in 15 patients. T level and N level down-staging were observed in 12 and 13 patients, respectively. A pathological complete response was observed in one patients. The median follow-up period was 75 months (range, 8-97 months). Recurrences occurred in 5 patients including pelvic relapses in 3 and distant metastases in 2. The 5-year relapse-free and overall survival rates were 74% and 84%, respectively.. Neoadjuvant systemic chemotherapy comprised of a combination of multi-drugs as irinotecan, 5-FU, and LV may be beneficial to the prognoses of patients with locally advanced rectal cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Drug Administration Schedule; Female; Fluorouracil; Follow-Up Studies; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Rectal Neoplasms; Time Factors; Treatment Outcome

Standard adjuvant chemoradiotherapy of rectal cancer still consists of 5-fluorouracil (5-FU) only. Its cytotoxicity is enhanced by folinic acid (FA) and interferon-α (INFα). In this trial, the effects of FA and IFNα on adjuvant 5-FU chemoradiotherapy in locally advanced rectal cancer were investigated.. Patients with R(0)-resected rectal cancer (UICC stage II and III) were stratified and randomised to a 12-month adjuvant chemoradiotherapy with 5-FU, 5-FU+FA, or 5-FU+IFNα. All patients received levamisol and local irradiation with 50.4 Gy.. Median follow-up was 4.9 years (n=796). Toxicities (WHO III+IV) were observed in 32, 28, and 58% of patients receiving 5-FU, 5-FU+FA, and 5-FU+IFNα, respectively. No differences between the groups were observed for local or distant recurrence. Five-year overall survival (OS) rates were 60.3% (95% confidence interval (CI): 54.3-65.8), 60.4% (54.4-65.8), and 59.9% (53.0-66.1) for 5-FU, 5-FU+FA, and 5-FU+IFNα, respectively. A subgroup analysis in stage II (pT3/4pN0) disease (n=271) revealed that the addition of FA tended to reduce the 5-year local recurrence (LR) rate by 55% and increase recurrence-free survival and OS rates by 12 and 13%, respectively, relative to 5-FU alone.. Interferon-α cannot be recommended for adjuvant chemoradiotherapy of rectal cancer. In UICC stage II disease, the addition of FA tended to lower LR and increased survival. The addition of FA to 5-FU may be an effective option for adjuvant chemoradiotherapy of UICC stage II rectal cancer.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Algorithms; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Disease Progression; Female; Fluorouracil; Humans; Interferon-alpha; Leucovorin; Male; Middle Aged; Radiotherapy, Adjuvant; Rectal Neoplasms; Young Adult

To assess the efficacy and safety of bevacizumab plus irinotecan-based regimen for the first line treatment in metastatic colorectal cancer (mCRC) patients, and to investigate the correlation between serum tumor markers including CEA and CA19-9 and response as well as prognosis.. From May 2007 to July 2008, 67 previously untreated mCRC patients received treatment of IFL (n = 25), IFL plus Bevacizumab (n = 20) or FOLFIRI (n = 22). The treatment continued until disease progression or unacceptable toxicity. The data were retrospectively analyzed.. All patients were evaluable for response, survival and toxicity analysis. The objective response rate of IFL, IFL plus Bevacizumab or FOLFIRI regimen groups was 16.0% (4/25), 35.0% (7/20) and 18.2% (4/22), respectively (χ(2) = 6.026, P = 0.049). The median progression-free survival (PFS) of IFL plus bevacizumab group was 7.5 months, significantly improved as compared with 3.7 months in the IFL group and 4 months in FOLFIRI group (χ(2) = 11.97, P = 0.003). Of all 67 cases, the one-year survival rate was 47.0%, two-year survival rate was 27.0%, and the median overall survival (OS) was 13.0 months, with no significant difference among the three treatment groups (χ(2) = 3.42, P = 0.18). The serum CEA and CA19-9 levels were decreased after treatment, but with no significant difference among the three groups (P > 0.05). The common toxicity profiles of IFL and FOLFIRI regimens were diarrhea and neutropenia, while the toxicity related to bevacizumab was consistent with that documented in previous literature, such as hypertension, hemorrhage, cardiac toxicity and delayed wound healing.. The addition of bevacizumab to irinotecan-based regimen significantly improves the response rate and PFS in first-line treatment for patients with mCRC and its toxicity is well tolerated.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adult; Aged; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; CA-19-9 Antigen; Camptothecin; Carcinoembryonic Antigen; Colonic Neoplasms; Diarrhea; Disease-Free Survival; Female; Fluorouracil; Follow-Up Studies; Humans; Hypertension; Irinotecan; Leucovorin; Male; Middle Aged; Neutropenia; Rectal Neoplasms; Remission Induction; Retrospective Studies; Survival Rate; Young Adult

Oxaliplatin combined with either fluorouracil/leucovorin (OXAFAFU) or capecitabine (OXXEL) has a demonstrated activity in metastatic colorectal cancer patients. We aimed at comparing these two regimens in terms of response rate (RR), safety, progression-free survival (PFS), and quality of life (QoL) of patients.. A total of 322 patients with metastatic colorectal cancer were randomized to receive biweekly: oxaliplatin 100 mg/m(2) i.v. on day 1, capecitabine 1,000 mg/m(2) orally twice daily from day 1 to day 11 (OXXEL); or oxaliplatin 85 mg/m(2) i.v. on day 1; 6S-leucovorin 250 mg/m(2) i.v. and fluorouracil 850 mg/m(2) i.v. on day 2 (OXAFAFU).. Eleven complete and 42 partial responses were registered with OXXEL (RR = 34%); six complete and 48 partial responses were obtained with OXAFAFU (RR = 33%) (P = 0.999). Severe adverse events were less frequent (32 vs. 43%) with OXXEL, which also reduced the occurrence of severe neutropenia (10 vs. 27%) and febrile neutropenia (6 vs. 13%), but produced more gastric side effects (8 vs. 3%) and diarrhea (13 vs. 8%). QoL did not differ across the two arms. Median PFS was 6.6 months in the OXXEL, and 6.5 months in the OXAFAFU arm (HR = 1.12, P = 0.354). Median overall survival was 16.0 and 17.1 months (HR = 1.01, P = 0.883).. OXXEL and OXAFAFU regimens were equally active in metastatic colorectal cancer. The choice should be based on patient preference and on pharmacoeconomic evaluations.

Topics: Adenocarcinoma; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Colonic Neoplasms; Colorectal Neoplasms; Deoxycytidine; Disease Progression; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Quality of Life; Rectal Neoplasms; Survival Analysis; Time Factors

The purpose of this study was to assess the longitudinal impact of stoma formation on the health-related quality of life of rectal cancer patients treated with adjuvant chemotherapy.. Health-related quality of life data was prospectively collected in a randomized trial designed to compare 24 weeks of bolus 5-fluorouracil/leucovorin with 12 weeks of continuous 5-fluorouracil in patients with resected Dukes B and C colorectal cancer. Health-related quality of life data was collected at baseline, during adjuvant treatment, and at one and three years after completion of chemotherapy.. Between 1993 and 2003, 186 rectal cancer patients were enrolled. One hundred thirty-nine patients had anterior resection, of whom 46 had a temporary defunctioning colostomy. Forty-seven patients had abdominoperineal resection with formation of a permanent colostomy. There was no significant difference in global health-related quality of life between patients with and patients without a stoma at any time point. However, during adjuvant treatment, role (P = 0.04) and social (P = 0.005) functioning were significantly worse in stoma patients than in nonstoma patients. Moreover, the impairment in social functioning persisted at one (P = 0.03) and three years (P = 0.04) after adjuvant chemotherapy.. Our results demonstrate important adverse effects of either temporary or permanent stoma formation on subsequent health-related quality of life in patients with rectal cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colostomy; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Postoperative Period; Quality of Life; Rectal Neoplasms

Irinotecan (CPT-11), oxaliplatin, 5-fluorouracil (5-FU) and capecitabine are main active agents for advanced colorectal cancer. FORFIRI regimen is recommended for the patients who were treated with oxaliplatin plus 5-FU or capecitabine previously. This study was to investigate the efficacy and safety of FORFIRI regimen in treating advanced colorectal cancer failing to prior oxaliplatin-based chemotherapy, and analyze the impacts of clinical factors on the responses.. A total of 90 patients with advanced colorectal adenocarcinoma, who had received prior adjuvant FOLFOX6 regimen and progressed within 12 months after the completion of therapy or had no response to prior FOLFOX6/CapeOX regimen as first-line therapy, were treated with FORFIRI regimen. The efficacy and adverse events were observed.. Of the 81 evaluable patients, two achieved complete remission, 20 achieved partial remission and 34 had stable disease. The overall response rate was 27.2% and disease control rate was 69.1%. The median time to progression was 6.8 months (95% CI, 4.9-8.8 months) and median overall survival time was 18.8 months (95% CI, 17.5-20.2 months). The main adverse events time were nausea, vomiting, neutropenia, alopecia, fatigue, impaired liver function, oral mucositis and diarrhea. Grade III adverse events included alopecia in 15 patients (16.7%), vomiting in 10 patients (11.1%), nausea in eight patients (8.9%), neutropenia in five patients (5.6%), impaired liver function in two patients (2.2%) and oral mucositis in two patients (2.2%).. FOLFIRI regimen is effective and well-tolerated as salvage therapy for advanced colorectal cancer failing to prior FOLFOX6/CapeOX regimen, and thus can be used widely.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Disease Progression; Female; Fluorouracil; Follow-Up Studies; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Nausea; Neoplasm Staging; Neutropenia; Rectal Neoplasms; Remission Induction; Salvage Therapy; Survival Rate; Vomiting; Young Adult

Although chemoradiotherapy plus resection is considered standard treatment for operable rectal carcinoma, the optimal time to administer this therapy is not clear. The NSABP R-03 (National Surgical Adjuvant Breast and Bowel Project R-03) trial compared neoadjuvant versus adjuvant chemoradiotherapy in the treatment of locally advanced rectal carcinoma.. Patients with clinical T3 or T4 or node-positive rectal cancer were randomly assigned to preoperative or postoperative chemoradiotherapy. Chemotherapy consisted of fluorouracil and leucovorin with 45 Gy in 25 fractions with a 5.40-Gy boost within the original margins of treatment. In the preoperative group, surgery was performed within 8 weeks after completion of radiotherapy. In the postoperative group, chemotherapy began after recovery from surgery but no later than 4 weeks after surgery. The primary end points were disease-free survival (DFS) and overall survival (OS).. From August 1993 to June 1999, 267 patients were randomly assigned to NSABP R-03. The intended sample size was 900 patients. Excluding 11 ineligible and two eligible patients without follow-up data, the analysis used data on 123 patients randomly assigned to preoperative and 131 to postoperative chemoradiotherapy. Surviving patients were observed for a median of 8.4 years. The 5-year DFS for preoperative patients was 64.7% v 53.4% for postoperative patients (P = .011). The 5-year OS for preoperative patients was 74.5% v 65.6% for postoperative patients (P = .065). A complete pathologic response was achieved in 15% of preoperative patients. No preoperative patient with a complete pathologic response has had a recurrence.. Preoperative chemoradiotherapy, compared with postoperative chemoradiotherapy, significantly improved DFS and showed a trend toward improved OS.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Digestive System Surgical Procedures; Disease-Free Survival; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Preoperative Care; Radiotherapy, Adjuvant; Rectal Neoplasms

Addition of chemotherapy in the resting period between radiotherapy completion and response assessment during neoadjuvant treatment for distal rectal cancer could potentially increase rates of complete tumor regression. The purpose of this study was to evaluate toxicity rates and the impact of an extended neoadjuvant chemoradiation regimen on complete response rates.. Thirty-four consecutive patients with nonmetastatic distal rectal cancer were prospectively included. Patients were managed by 5,400 Gy of radiation and 5-fluorouracil/leucovorin-based chemotherapy given for three consecutive days every 21 days for six cycles (three cycles concomitant with radiotherapy). Tumor response assessment was performed at ten weeks from radiation completion. Patients with complete clinical response were strictly monitored and were not immediately operated on. Patients with incomplete clinical response were referred to surgery.. Twenty-nine patients had completed 12 months of follow-up and were included in this preliminary analysis. Twenty-eight (97%) successfully completed treatment. Fifteen of 16 patients had Grade III toxicities that were skin-related (93%). Median follow-up was 23 months. Fourteen patients (48%) were considered as complete clinical responders sustained for at least 12 months (median, 24 months) after chemoradiation completion by clinical assessment alone. An additional five patients (17%) were considered as complete responders with ypT0 results after full-thickness local excision. Overall, the complete response rate was 65%.. The addition of chemotherapy during the resting period after neoadjuvant chemoradiation is associated with acceptable toxicity and high tolerability rates. The considerably high rates of complete response in this preliminary series requires further follow-up, but they may provide valuable information for future prospective, randomized trials.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Radiotherapy Dosage; Rectal Neoplasms

The primary objective was to compare the 3-year survival of rectal cancer patients randomised postoperatively to irinotecan (IRI), Leucovorin (LV) and bolus 5-fluorouracil (5FU) or LV-bolus 5FU with radiotherapy. Secondary objectives included disease-free survival, local relapse and toxicity. The study included 321 eligible patients. The treatment consisted of weekly administration of IRI 80 mg/m(2) intravenously (IV), LV 200 mg/m(2) and 5FU 450 mg/m(2) bolus (arm A) versus LV 200 mg/m(2) and 5FU 450 mg/m(2) IV bolus (arm B). One cycle included four infusions and treatment was continued for a total of six cycles. The first cycle was followed by pelvic irradiation plus 5FU. There were no differences between the arms in 3-year overall, disease-free and local relapse-free survival. Grades 3 and 4 toxicity was similar in both the arms with the exception of leucopaenia, neutropaenia and alopecia, which were higher in the IRI arm. IRI added to adjuvant radiochemotherapy with LV and bolus 5FU was not shown to improve survival, whereas the incidence of severe leucopaenia was significantly higher in the IRI arm.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Cohort Studies; Drug Administration Schedule; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Radiotherapy, Adjuvant; Rectal Neoplasms; Survival Analysis; Treatment Outcome

To evaluate the efficacy and safety of an adjuvant chemotherapy regimen: XELOX (Capecitabine puls Oxaliplatin) used after curative resection for stage III colorectal cancer.. From Jan. 1998 to Jan. 2004, 256 cases with stage III colorectal cancer randomized received de Gramont, modified FOLFOX4 (mFOLFOX4) and XELOX regimens. The 3-year disease-free survival (DFS) and overall survival (OS) were compared within the three groups and relative prognosis factors within mFOLFOX4 and XELOX groups. Therapeutic adverse events were recorded and analyzed with Kaplan-Meier test.. 98, 87 and 71 cases were respectively enrolled in the de Gramont, mFOLFOX4 and XELOX groups, mFOLFOX4 and XELOX had superior efficacy compared with de Gramont regimen. The two former could significantly improve 3-year DFS (79.7% vs. 66.2%, P = 0.015; 81.5% vs. 66.2%, P = 0.004) and medium survival time (40.2 mon vs. 37.8 mon, P = 0.024; 41.4 mon vs. 37.8 mon, P = 0.014). Meanwhile they could respectively decrease the ratio of recurrence risk by 18.0% (P = 0.024) and 21.0% (P = 0.003). The relative benefit of mFOLFOX4 versus XELOX didn't differ for 3-year DFS [hazard ratio (HR): 0.84, 95% confidence interval (CI): 0.79-1.12, P = 0.13] and OS (HR: 0.87, 95% CI: 0.84-1.06, P = 0.54). In the analysis of DFS in relative prognosis factors, XELOX had a better trend of survival advantage. mFOLFOX4 had higher adverse events within these regimens, especially in grade 3 or 4 neutropenia and peripheral neurologic adverse events.. XELOX maintains its efficacy and safety ratio in advanced colorectal cancer. Patients have good tolerance and compliance. The regiment is deserves to be applied in clinical treatment. Oxaliplatin;

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemotherapy, Adjuvant; Colonic Neoplasms; Deoxycytidine; Disease-Free Survival; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Oxaloacetates; Proportional Hazards Models; Rectal Neoplasms; Retrospective Studies; Survival Rate; Young Adult

Preoperative chemoradiotherapy is considered standard treatment for locally advanced rectal cancer, although the scientific evidence for the chemotherapy addition is limited. This trial investigated whether chemotherapy as part of a multidisciplinary treatment approach would improve downstaging, survival, and relapse rate.. The randomized study included 207 patients with locally nonresectable T4 primary rectal carcinoma or local recurrence from rectal carcinoma in the period 1996 to 2003. The patients received either chemotherapy (fluorouracil/leucovorin) administered concurrently with radiotherapy (50 Gy) and adjuvant for 16 weeks after surgery (CRT group, n = 98) or radiotherapy alone (50 Gy; RT group, n = 109).. The two groups were well balanced according to pretreatment characteristics. An R0 resection was performed in 82 patients (84%) in the CRT group and in 74 patients (68%) in the RT group (P = .009). Pathologic complete response was seen in 16% and 7%, respectively. After an R0 + R1 resection, local recurrence was found in 5% and 7%, and distant metastases in 26% and 39%, respectively. Local control (82% v 67% at 5 years; log-rank P = .03), time to treatment failure (63% v 44%; P = .003), cancer-specific survival (72% v 55%; P = .02), and overall survival (66% v 53%; P = .09) all favored the CRT group. Grade 3 or 4 toxicity, mainly GI, was seen in 28 (29%) of 98 and six (6%) of 109, respectively (P = .001). There was no difference in late toxicity.. CRT improved local control, time to treatment failure, and cancer-specific survival compared with RT alone in patients with nonresectable rectal cancer. The treatments were well tolerated.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Europe; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Radiotherapy, Adjuvant; Rectal Neoplasms; Survival Analysis; Time Factors; Treatment Failure; Treatment Outcome

Oxaliplatin is a platinum analog and radiosensitizer active in colorectal cancer. We performed a Phase I trial to test the safety and preliminary efficacy of adding oxaliplatin to standard preoperative chemoradiation therapy for rectal cancer.. Eligible patients had T3 to T4 rectal adenocarcinoma. Patients received standard-dose radiation (50.4 Gy for 5.5 weeks) with concurrent infused 5-fluorouracil (5-FU) at 200 mg/m2 per day, 7 days per week. Oxaliplatin was given three times at 14-day intervals at 55, 70, or 85 mg/m2 during the 5.5-week radiation period, before resection. Adjuvant therapy consisted of four cycles of 5-FU (500 mg/m2 per week) with leucovorin (500 mg/m2 per week) given every 6 weeks. The main goals were to identify the maximum tolerated dose of oxaliplatin and the dose-limiting toxicities when given with 5-FU and RT. Secondary goals were to determine resectability, pathologic response, sphincter preservation, and overall survival rates.. Twenty-one patients were enrolled, 5 at the 55 mg/m2 oxaliplatin dose level, 5 at 70 mg/m2, and 11 at 85 mg/m2. All patients were able to complete the preoperative chemoradiation regimen with no dose adjustments. No dose-limiting toxicities or differences in the type or extent of toxicity were noted among the groups. Nineteen patients underwent surgery (three abdominopelvic resections and 16 low anterior resections), for an 84% sphincter preservation rate. The pathologic complete response rate was 26% (5 patients), and minimal microscopic residual tumor was found in 21% (4 additional patients).. Oxaliplatin was well tolerated at 85 mg/m2 given every 2 weeks in combination with standard preoperative chemoradiation for rectal cancer. The rates of major pathologic response and sphincter preservation are promising.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Neoplasm, Residual; Organoplatinum Compounds; Oxaliplatin; Radiation-Sensitizing Agents; Rectal Neoplasms

Irinotecan (CPT-11), a specific inhibitor of topoisomerase I, has been proven to be effective in the treatment of refractory or metastatic colorectal cancer. Furthermore, several first line phase III trials of the combination therapy (FOLFIRI) using CPT-11 and fuorouracil/leucovorin (5-Fu/LV) were reported to have significant improvement in treatment result. Therefore, we designed a multicenter clinical study to observe the overall survival (OS), time to death (TTD), time to progression (TTP), efficacy and safety of FOLFIRI regimen for patients with refractory or metastatic colorectal cancer after first line chemotherapy failure.. Patients with metastatic or refractory colorectal cancer after first line oxaliplatin-based chemotherapy failure were enrolled into this prospective, one arm and open-labeled multicenter study. Irinotecan 180 mg/m2 was administered biweekly on D1, LV 200 mg/m2 by intravenous infusion in 2 hours before bolus intravenous injection of 5-Fu 400 mg/m2, then followed immediately by intravenous infusion of 5-Fu 2.4 g/m2 in 46 hours. OS, TTD, TTP, response rate (RR) and adverse events were assessed according to RSCIST criteria and NCIC-CTG CTCAE (3.0).. Sixty-six patients were valuable for safety assessment and and 61 for efficacy. There was no CR patient in this series. Ten patients had PR, 35 SD (57.4% ) and 16 PD (26.2%) with a response rate of 16.4% (10/61). The median TTP was 5.0 months (1-12 months), median TTD 9.9 months (5-27 months)and median OS 18.2 months (7-33 months). The adverse events including nausea,vomiting, anorexia,diarrhea, leucopenia and cholinergic syndrome were frequent, but usually in I - II degree. The rate of III/IV degree diarrhea and leucopenia was 7.6% and 22.7%, respectively.. The regimen of irinotecan plus fuorouracil/leucovorin (FOLFIRI) is effective and well-tolerated as a second-line chemotherapy and may prolong the overall survival for the patient with refractory or metastatic colorectal cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Disease Progression; Female; Fluorouracil; Follow-Up Studies; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neutropenia; Prospective Studies; Rectal Neoplasms; Remission Induction; Survival Rate; Vomiting; Young Adult

The primary end-point of our randomized trial was sphincter preservation. The secondary aim was to evaluate whether distal bowel clearance < or =1 cm is safe after radiation.. The study randomized 312 patients with cT3-4 resectable low-lying and mid-rectal cancer to receive either preoperative irradiation (5 x 5 Gy) with immediate total mesorectal excision (TME) or chemoradiation (50.4 Gy, bolus 5-fluorouracil and leucovorin) with delayed TME. After anterior resection, pathologists prospectively measured macroscopic and microscopic distal bowel clearance.. Macroscopic and microscopic distal bowel clearance, distal intramural spread, sphincter preservation, local control, disease-free survival, and overall survival did not differ in the two randomized groups. Pooled analysis of the two groups showed that the incidence of local recurrence at 4 years (median follow-up) for patients with macroscopic clearance < or =1 cm (n = 42) and >1 cm (n = 124) was 11.3% and 15.4%, respectively (P = 0.514); the hazard ratio (HR) was 0.70, and the 95% confidence interval (CI) was 0.23-2.07. The corresponding values for patients with microscopic clearance < or =1 cm (n = 51) and >1 cm (n = 101) were 9.6% and 17.6% (P = 0.220; HR 0.51; 95% CI 0.17-1.53).. After preoperative radiotherapy, distal bowel clearance < or =1 cm did not compromise local control.

Topics: Adult; Aged; Anal Canal; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Intestines; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Preoperative Care; Prognosis; Prospective Studies; Rectal Neoplasms; Survival Rate; Treatment Outcome

The aim this study was to determine the pathologic complete response (pCR) rate defined as tumor regression grade 1 (TRG1) and toxicity profile of the combination of high-dose pre-operative radiotherapy and simultaneous UFT/leucovorin (LV) in patients with locally advanced rectal cancer.. Eligibility included biopsy proven rectal adenocarcinoma; T3-T4 N0-N2; performance status < 2 (ECOG) and adequate blood, hepatic and renal function. Treatment consisted of radiotherapy 54 Gy at 1.8 Gy/day and UFT 300 mg/m(2)/day and LV 60 mg/day, given simultaneously daily for 6 weeks. Surgery was performed within 4-6 weeks period after chemoradiotherapy. Patients who did not achieve TGR1 were to receive 4 cycles of adjuvant UFT/LV on days 1-28, every 5 weeks.. Sixty-eight patients were included. All but one received full dose of radiation and 62 had the total planned pre-operative UFT/LV dose. Grade 3 toxicities were diarrhea 7% and proctitis 3%. Complete resection was achieved in 62 patients (91%). Tumor regression grade 1 (TRG1) was seen in 11 patients (16%). Forty-eight patients received adjuvant UFT/LV. Grade 3 toxicity during adjuvant UFT/LV included diarrhea 12%, asthenia 4%, neutropenia 2%, and hand-foot syndrome 2%. The 3-year disease-free survival was 71%.. Simultaneous high-dose pre-operative localized radiation therapy concurrent with UFT/LV is feasible and has a low toxicity profile. This schedule is highly effective and merits further investigation.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Humans; Leucovorin; Male; Middle Aged; Rectal Neoplasms; Tegafur; Treatment Outcome; Uracil

The objective of this expanded phase II trial was to confirm the safety results of the preceding phase I study and establish the efficacy of neoadjuvant radiochemotherapy with capecitabine in rectal cancer in a multicenter setting.. 96 patients (63% male, age 34-81 years) with advanced rectal cancer (cT3-4 or cN+) from seven university centers in Germany were recruited. All were to receive a total irradiation dose of 50.4-55.8 Gy with conventional fractions. Capecitabine was given at an oral dosage of 825 mg/m(2)bid on each day of the radiotherapy period with the first daily dose applied 2 h before irradiation, followed by surgery 6 weeks later.. Most of the patients suffered from an advanced primary tumor (cT3: 57%, cT4: 40%) with lymph node involvement in 60%. After neoadjuvant treatment, with a mean of 99% of the scheduled radiation dose actually delivered, a clinical response rate of 68% (95% confidence interval: 57-78%) was observed. Out of 87 evaluable patients undergoing surgery, a sphincter-preserving procedure could be performed in 51% and R0 resection in 94%. A pathologically complete response was achieved in six patients (7%, 95% confidence interval: 3-14%). The comparison of initial diagnosis and pathologic findings showed a downstaging in 61%. Acute toxicity with > 5% incidence of NCI (National Cancer Institute) grade >/= 3 included lymphopenia (12%), leukopenia (6%), and diarrhea (7%). Mild to moderate hand-foot syndrome occurred in 12% only. After a median follow-up of 48 months, the 5-year overall survival and tumor control data were, with regard to patient selection, in the expected range with an overall survival of 65%, a relapse-free survival of 47%, and a local recurrence rate after 5 years of 17%.. The data clearly confirm that capecitabine is an adequate substitute for 5-fluorouracil in preoperative chemoradiation of rectal cancer with a favorable safety profile.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Capecitabine; Chemotherapy, Adjuvant; Deoxycytidine; Disease-Free Survival; Dose Fractionation, Radiation; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Proctocolectomy, Restorative; Radiotherapy Planning, Computer-Assisted; Rectal Neoplasms; Rectum

To compare, in a randomized trial, 5-fluorouracil (FU) plus leucovorin (LV) (FU+LV) vs. oral uracil and tegafur (UFT) plus LV (UFT+LV) given concomitantly with preoperative irradiation in patients with cT3-4 or N+ rectal cancer.. A total of 155 patients were entered onto the trial. Patients received pelvic radiotherapy (4500-5,040 cGy in 5 to 6 weeks) and chemotherapy consisting of two 5-day courses of 20 mg/m(2)/d LV and 350 mg/m(2)/d FU in the first and fifth weeks of radiotherapy (77 patients) or one course of 25 mg/d oral LV and 300 mg/m(2)/d UFT for 4 weeks beginning in the second week of radiotherapy (78 patients). The primary endpoints were pathologic complete response (pCR) and resectability rate. Secondary endpoints included downstaging rate, toxicity, and survival.. Grade 3-5 acute hematologic toxicity occurred only with FU+LV (leukopenia 9%; p = 0.02). There were no differences in resectability rates (92.1% vs. 93.4%; p = 0.82). The pCR rate was 13.2% in both arms. Tumor downstaging was more frequent with UFT+LV (59.2% vs. 43.3%; p = 0.04). Three-year overall survival was 87% with FU+LV and 74% with UFT+LV (p = 0.37). The 3-year cumulative incidences of local recurrence were 7.5% and 8.9%, respectively (p = 0.619; relative risk, 1.46; 95% confidence interval 0.32-6.55).. Although this study lacked statistical power to exclude clinically significant differences between both groups, the outcome of patients treated with UFT+LV did not differ significantly from that of patients treated with FU+LV, and hematologic toxicity was significantly lower in the experimental arm.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Disease-Free Survival; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Neoplasm Staging; Preoperative Care; Prospective Studies; Radiotherapy Dosage; Rectal Neoplasms; Survival Analysis; Tegafur; Uracil; Vitamin B Complex

Preoperative radiochemotherapy is a cornerstone in patients with non- resectable locally advanced rectal cancer (LARC). To improve outcome (number of R0 resections and survival) high-dose radiotherapy (RT) was combined with oral UFT/l-leucovorin to allow tumour regression before radical intended surgery.. Pelvic RT was delivered with megavoltage photons using a 5 field technique. RT was CT-based, given 5 days a week through one posterior field and two lateral fields (48.6 Gy/27 fractions) to encompass the primary tumour and the regional lymph nodes. In addition, the tumour bed received a concurrent boost (5.4 Gy/27 fractions) and a final boost (6 Gy/3 fractions); thus GTV received 60 Gy/30 fractions. Concurrent with RT patients received a daily dose of oral UFT 300 mg/m(2) plus l-leucovorin 22.5 mg 5/7 days (divided in three doses).. From September 2000 to November 2004, 52 patients (median age 60 years (32-83); median PS 0 (0-2)) with LARC (36 primary, 16 recurrent) were included in this phase II study. All but three patients received the planned 60 Gy, median duration of RT was 42 days (25-49). Toxicity was very modest; only four patients had a dose reduction of UFT. No hematological toxicity of clinical significance was seen. Non-hematological toxicity grade 1 (GI-toxicity, fatigue and/or dysuria) was frequently observed but only four patients experienced grade 3 toxicity (diarrhoea and/or nausea/vomiting). Forty patients (77%) were operated (30 R0, 5 R1, 5 R2) median 55 days (27-112) after completion of RT. Seven (13%) patients had a pathological complete response (pCR). Thirty-one patients (60%) died after median 25.4 months (1.6-45.2 months). Twenty-one patients (40%) are still alive June 2007.. Preoperative high-dose RT and concomitant UFT produces major regression in most patients with non-resectable LARC and thus a good chance of cure.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Dose Fractionation, Radiation; Drug Combinations; Female; Gastrointestinal Diseases; Hematologic Diseases; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Preoperative Care; Radiotherapy, Adjuvant; Radiotherapy, High-Energy; Rectal Neoplasms; Survival Analysis; Tegafur; Treatment Outcome; Uracil

The objective of this study was to evaluate the maximum tolerated dose (MTD) and recommended dose of irinotecan administered as a 5-day schedule synchronously with 5-fluorouracil (5FU), leucovorin (LV) and preoperative pelvic radiation (45 Gy) for primary borderline/unresectable, locally advanced rectal cancer. The study used escalating doses of intravenous irinotecan (6, 8, 10, 12, 14, 16, 18, and 20 mg m(-2)) administered on days 1-5 and 29-33 followed by low dose LV (20 mg m(-2)) and 5FU (350 mg m(-2) over 1 h) in sequential cohorts. Preoperative pelvic radiotherapy using a three- or four-field technique and megavoltage photons comprised 45 Gy given in 25 fractions, 1.8 Gy per fraction. Surgery in the form of mesorectal excision was performed 6-10 weeks later. Histopathological examination of the resected specimen was performed according to techniques of Quirke, and compared with clinical staging. A distance of 1 mm or less between the peripheral extent of the tumour and the radial resection margin defined an involved circumferential resection margin (CRM). The MTD was determined as the dose causing more than a third of patients to have a dose-limiting toxicity (DLT) defined as specific grade 3 or 4 toxicities. Once the MTD was reached, a further 14 patients were treated at the dose level below the MTD. In total, 57 patients received irinotecan at the eight dose levels. The final cohort reached DLT after only four patients had been enrolled. The median age was 62 years (range 26-75), 37 male and 20 female subjects. The MTD of irinotecan in this schedule was 20 mg m(-2) when three out of four patients experienced DLT. Dose limiting grade 3 or 4 diarrhoea was reported in seven out of 57 patients, three at the 20 mg m(-2) dose level. Serious haematological toxicity (grade 3) was minimal and reported in only three patients; one grade 3 neutropaenia, one grade 4 neutropaenia and one grade 3 febrile neutropaenia and anaemia. Compliance was good with 93 and 89% of patients completing radiotherapy and chemotherapy, respectively. The remaining patients had only minor deviations from protocol therapy. Eight patients did not proceed to surgery, in six cases because they remained unresectable or had developed metastatic disease, one patient was unfit for surgery and one died as a result of complications from radiotherapy. Forty-nine patients underwent a potentially curative surgical resection. Histopathological examination of the resected specimen demonstrated pCR

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cohort Studies; Combined Modality Therapy; Disease Progression; Disease-Free Survival; Drug Administration Schedule; Female; Fluorouracil; Follow-Up Studies; Humans; Irinotecan; Leucovorin; Magnetic Resonance Imaging; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Recurrence, Local; Pelvic Neoplasms; Rectal Neoplasms; Sensitivity and Specificity; Survival Rate; Treatment Outcome

Between 1996 and 2000, the colorectal tumour committee of the Hospital Universitario de Bellvitge and the Institut Català d'Oncologia, Hospitalet, carried out a non-randomised prospective study of pre-op radio-chemotherapy (RT-CT) in locally advanced rectal tumours. We herein present the results. On the other hand, and at the same time, patients operated on for locally advanced rectal cancer were admitted and treated by RT-CT during the postoperative process, according to our standard protocol. Results for both series are compared.. The preoperative RT-CT group included 94 patients. They received radiotherapy (RT), 45 Gy on posterior pelvis, and simultaneously, 5-fluorouracil (5FU) by continuous infusion (300 mg/m2/day, 5 days weekly during RT). Surgical intervention was scheduled 6-8 weeks after preoperative treatment; after surgery they received 5FU (425 mg/m2/day) and leucovorin (20 mg/m2/day) bolus, 5 days weekly; 4 cycles at four-week intervals. 237 patients who had been previously operated on and who had been staged as T3-T4 and/or N+, M0 were admitted to our centre during the same time period and received postoperative RT-CT.. The preoperative treatment group showed a complete and global response rate to RT-CT in 17% and 68% of cases, respectively. Anal sphincter was preserved in 38.5% of patients exhibiting low rectal tumours (inferior limit of tumour at 6 cm or less from the anal margin). Overall and disease-free survival at 5 years was distinct, showing statistical significance, according to the response obtained through preop treatment; it was better in responsive patients (overall survival: 87% in complete remissions, 75% in partial remissions, 48% in stable disease, and mean survival was 0.84 years for patients who evolved, p<0.05; disease-free survival was: 93% in complete remission, 76% partial remission, 39% in stable disease, p=0.001). We did not see any difference with regard to overall survival, disease-free survival or local control at the time of comparing either pre- or postoperative groups. There were, however, differences with regard to late toxicity; they showed less toxicity when RT-CT was administered preoperatively; no case of radiation enteritis that required surgery was seen in this group, whereas in the postoperative RT-CT it was 4.2%, p=0.022.. Preoperative treatment of locally advanced rectal cancer is recommended, for it yields a high level of response to treatment; it allows preservation surgery of the anal sphincter in one third of patients showing low rectal tumours. There is also a clear diminution of late toxicity with pre-op treatment. On the other hand, response to pre-op treatment selects patients with a better prognosis.

Topics: Adenocarcinoma; Amputation, Surgical; Antimetabolites, Antineoplastic; Colostomy; Combined Modality Therapy; Disease-Free Survival; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Neoadjuvant Therapy; Palliative Care; Pelvic Exenteration; Preoperative Care; Prospective Studies; Rectal Neoplasms; Survival Analysis; Treatment Outcome

Preoperative chemotherapy followed by surgery and adjuvant chemotherapy is a standard treatment for most patients with rectal cancer. We aimed to determine efficacy and tolerability of preoperative mitomycin, fluorouracil (5-FU), and leucovorin (LV) concurrent with hyperfractionated radiation therapy (RT) followed by surgery and adjuvant chemotherapy.. Patients with clinical stage II/III disease were treated with mitomycin 10 mg/m(2) on day 1, continuous venous infusion 5-FU 600 mg/m(2) per day for 96 hours, and oral LV 25 mg every 6 hours on days 1-5. All patients received concurrent RT in fractions of 150 cGy twice daily beginning on day 1. Unfixed tumors received 3000 cGy, whereas fixed tumors received a dose of 4500 cGy. Patients then underwent resection and postoperative adjuvant chemotherapy with oral LV and continuous venous infusion 5-FU 600 mg/m(2) per day on days 1-5 on a 28-day cycle for 6 cycles. Primary endpoints were to determine the rate of pathologic response and downstaging, long-term locoregional control, progression-free survival, and overall survival.. Between the years 1993 and 2000, 83 patients were enrolled. Eighteen patients (31%) were downstaged. Six patients (7%) had pathologic complete response. Median follow-up was 62 months with a 5-year overall survival of 71%. Local control rate was 96%. Treatment was well tolerated with stomatitis, diarrhea, and radiation proctitis being the most common toxicities.. This regimen is effective in the treatment of rectal carcinoma. The favorable toxicity profile of mitomycin and hyperfractionated RT allows these strategies to be utilized with the newer chemotherapies for this disease.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Mitomycin; Neoadjuvant Therapy; Preoperative Care; Radiotherapy, Adjuvant; Rectal Neoplasms; Survival Analysis; Time Factors; Vitamin B Complex

Tissue inhibitor of metalloproteinase-1 (TIMP-1) is known to protect cells against apoptosis. We raised the hypothesis that elevated tumor tissue levels and thereby plasma levels of TIMP-1 would predict resistance to apoptosis-inducing chemotherapy.. Ninety patients with metastatic colorectal cancer were included in the study. Plasma TIMP-1 and serum carcinoembryonic antigen (CEA) were measured in samples obtained before the first cycle of chemotherapy.. Analysis of best objective response (complete or partial response versus stable or progressive disease) showed that patients with low plasma TIMP-1 had higher probability of obtaining an objective response [odds ratio (OR), 3.5; 95% confidence interval (95% CI), 1.4-8.5, P=0.007]. CEA treated as a continuous variable was also a statistically significant predictor of no response (OR, 1.3; 95% CI, 1.0-1.7, P=0.02, area under the curve 0.66) but much less so. Plasma TIMP-1 was the only significant covariate in a multivariable analysis of best objective response (OR, 3.6; 95% CI, 1.4-9.5; P=0.001). Plasma TIMP-1 scored as a continuous variable on the log scale (log(e)) was significantly associated with overall survival [OS; hazard ratio (HR), 3.8; 95% CI, 2.4-5.9; P<0.0001] and with time to progression (TTP; HR, 1.5; 95% CI, 1.0-2.3; P=0.048). Multivariable analysis showed that plasma TIMP-1 was significant for OS when including routine clinical baseline covariates (HR, 3.5; 95% CI, 2.1-5.8; P<0.0001). A multivariable analysis including TTP instead of OS showed that only plasma TIMP-1 was retained in the model (HR, 1.5). CEA was not significantly associated with TTP or OS when TIMP-1 was included in the model.. This study shows that plasma TIMP-1 levels are significantly and independently associated with objective response, TTP, and OS in patients with metastatic colorectal cancer receiving combination chemotherapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Camptothecin; Carcinoembryonic Antigen; Colonic Neoplasms; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Neoplasm Metastasis; Odds Ratio; Rectal Neoplasms; Survival Analysis; Tissue Inhibitor of Metalloproteinase-1; Treatment Outcome

To evaluate comparative outcome between adjuvant postoperative chemoradiotherapy (postoperative CRT) and lateral pelvic lymph node dissection (LPLD) following total mesorectal excision (TME) in rectal cancer patients.. Although TME results in lower rate of locoregional recurrence compared with conventional surgery, these 2 treatment modalities following TME have not adequately been appraised until the present trend of preoperative chemoradiotherapy.. Between 1995 and 2000, patients with stage II and III rectal cancer underwent TME plus postoperative CRT (n = 309) or LPLD (n = 176). Patients in the postoperative CRT group received 8 cycles of 5-fluorouracil plus leucovorin and 45 Gy pelvic radiotherapy. Patients in the LPLD group underwent lateral lymph node dissection outside the pelvic plexus.. The 5-year overall and disease-free survival rates were 78.3% and 67.3% in the postoperative CRT group, respectively, and 73.9% and 68.6% in the LPLD group, respectively, without significant differences between these groups. Patients in the LPLD group with stage III lower rectal cancer had a locoregional recurrence rate 2.2-fold greater than those in the postoperative CRT group (16.7% vs. 7.5%, P = 0.044). Multivariate analysis showed that APR and advanced T-category (T4) were significantly associated with locoregional recurrence, whereas lymph node metastases, high preoperative serum carcinoembryonic antigen, and APR were significantly associated with shortening of disease-free survival.. Postoperative-CRT and LPLD following TME resulted in comparable survival rates, but the locoregional recurrence rate was higher in the LPLD group. These findings suggest that initial surgery is appropriate for rectal cancer patients who are candidates for low anterior resection without extensive local disease (T1-T3), regardless of lymph node status.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Digestive System Surgical Procedures; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Lymph Node Excision; Male; Middle Aged; Neoadjuvant Therapy; Pelvis; Radiotherapy Dosage; Rectal Neoplasms; Treatment Outcome; Vitamin B Complex

Recently, some scholars advocate perioperative chemotherapy for colorectal cancer. This study aimed to investigate the impact of perioperative chemotherapy on the prognosis of colorectal cancer.. From Aug. 2001 to Aug. 2003, 167 patients with Dukes'B or C colorectal cancer were randomized into two groups: 82 in trial group received perioperative chemotherapy using 5-fluorouracil (5-FU), while 85 in control group received no perioperative chemotherapy. All patients received adjuvant chemotherapy of 5-FU/leucovorin regimen. The adverse events, recurrence rate and survival rate were compared between these two groups.. There was no difference in adverse events between the two groups. The overall recurrence rate was 42.5%û it was significantly lower in trial group than in control group (34.6% vs. 49.4%, P=0.038). The overall 1-, 3-, and 4-year survival rates were 97.6%, 74.7% and 61.8%û they were significantly higher in trial group than in control group (100% vs. 95.3%, 82.7% vs. 67.1%, and 69.1% vs. 54.8%, P=0.046).. Perioperative chemotherapy can improve the prognosis of colorectal cancer.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colonic Neoplasms; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Perioperative Care; Rectal Neoplasms; Stomatitis; Survival Rate; Young Adult

The role of postoperative adjuvant chemotherapy in patients with rectal cancer pretreated by preoperative radiochemotherapy (RCT) and curative surgery is still poorly investigated.. We pooled data from both arms of a phase III trial in which patients with locally advanced (T3/4) rectal cancer were randomized to preoperative RCT alone or combined with pelvic radio-frequency hyperthermia. After surgery, R0-resected patients were scheduled to adjuvant chemotherapy with four monthly courses of 50 mg folinic acid (FA) and gradually escalated 5-fluorouracil (5-FU, 350-500 mg/m2, days 1-5). Reasons preventing initiation of chemotherapy and treatment-related toxicities were evaluated. Patients' characteristics and survival parameters were compared between the treated and untreated patient groups.. Out of 93 patients, 73 (79%) started adjuvant chemotherapy, whereas 19 (21%) did not, mostly due to perioperative complications and refusal. Chemotherapy-related toxicities were mild to moderate in most cases, but--together with protracted postoperative complications--prevented the intended dose escalation of 5-FU in 71% of patients. Distant-failure-free (p=0.03) and overall survival (p=0.03) were improved in the chemotherapy group, although there was a negative selection of patients with unfavourable characteristics into the untreated patient group.. Adjuvant chemotherapy using FA and 5-FU can be safely applied to the majority of patients with rectal cancer pretreated by RCT and surgery. Survival data are not suitable to allow far-reaching conclusions, but are in line with suggestions of a favourable effect of adjuvant chemotherapy in these patients.

Topics: Adolescent; Adult; Aged; Chemotherapy, Adjuvant; Colectomy; Drug Therapy, Combination; Female; Fluorouracil; Follow-Up Studies; Humans; Immunosuppressive Agents; Leucovorin; Male; Middle Aged; Postoperative Care; Radiotherapy, Adjuvant; Rectal Neoplasms; Retrospective Studies; Treatment Outcome; Vitamin B Complex

To evaluate the extent of distal intramural spread (DIS) after preoperative radiotherapy for rectal cancer.. A total of 316 patients with T(3-4) primary resectable rectal cancer were randomized to receive either preoperative 5x5 Gy radiation with immediate surgery or chemoradiation (50.4 Gy, 1.8 Gy per fraction plus boluses of 5-fluorouracil and leucovorin) with delayed surgery. The slides of the 106 patients who received short-course radiation and of the 86 who received chemoradiation were available for central microscopic evaluation of DIS.. The length of DIS did not differ significantly (p = 0.64) between the short-course group and the chemoradiation group and was 0 in 47% vs. 49%; 1 to 5 mm in 41% vs. 42%; 6 to 10 mm in 8% vs. 9%, and greater than 10 mm in 4% vs. 0, respectively. Among the 11 clinically complete responders, DIS was found 1 to 5 mm from the microscopically detected ulceration of the mucosa in 5 patients. The discontinuous DIS was more frequent in the chemoradiation group as compared with the short-course group (i.e., 57% vs. 16% of cases, p < 0.001).. Approximately 1 out of 10 advanced rectal cancers after preoperative radiotherapy or radiochemotherapy was characterized by DIS of over 5 mm. No significant difference was seen in the length of DIS between the 2 groups.

Topics: Adult; Aged; Anal Canal; Antimetabolites, Antineoplastic; Chi-Square Distribution; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Neoplasm, Residual; Radiotherapy Dosage; Rectal Neoplasms; Statistics, Nonparametric

Infusional fluorouracil (5-FU) and leucovorin (LV) with oxaliplatin is one of the current standard regimens for the treatment of patients with metastatic colorectal cancer. Weekly bolus 5-FU with high-dose LV (Roswell Park Memorial Institute Regimen: RPMI) is the most commonly used regimen in Japan. The objectives of this study were to determine the recommended dose (RD) of RPMI combined with oxaliplatin and to evaluate the toxicity and efficacy at the RD.. The subjects were 18 patients with metastatic colorectal cancer. Oxaliplatin (85 mg/m2) was given intravenously over 2 h on days 1 and 15 with l-LV (250 mg/m2) given intravenously over 2 h and 5-FU as an intravenous bolus on days 1, 8, and 15. This treatment was repeated every 4 weeks. The dose of 5-FU was escalated from 400 mg/m2 (level 1) to 500 mg/m2 (level 2).. A total of 14 patients received level 1, and 4 received level 2. Three of the patients had dose-limiting toxicity (DLT) in cycle 1 of level 2 (grade 3 thrombocytopenia, grade 4 neutropenia and grade 2 neutropenia in one patient each), requiring that treatment was delayed for longer than 7 days. None of the 14 patients given level 1 had DLT or grade 3 or 4 gastrointestinal toxicity. Sensory neuropathy occurred in all patients. Objective response rates were 61% in the 18 patients studied and 64% at level 1. The median time to progression was 171 days, and the median overall survival time was 603 days in the 18 patients studied.. Oxaliplatin (85 mg/m2) with weekly bolus 5-FU (400 mg/m2) and high-dose l-LV (250 mg/m2) is recommended for further phase III studies in patients with metastatic colorectal cancer.

Topics: Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Maximum Tolerated Dose; Middle Aged; Nausea; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Peripheral Nervous System Diseases; Rectal Neoplasms; Remission Induction; Survival Rate

To investigate the effect of three-dimensional conformal radiotherapy (3-DCRT) in combination with FOLFOX4 chemotherapy for unresectable recurrent rectal cancer.. Forty-eight patients with unresectable recurrent rectal cancer were randomized and treated by 3-DCRT or 3-DCRT combined with FOLFOX4 chemotherapy between September 2001 and October 2003. For the patients without prior radiation history, the initial radiation was given to the whole pelvis by traditional methods with tumor dose of 40 Gy, followed by 3-DCRT for the recurrent lesions to the median total cumulative tumor dose of 60 Gy (range 56-66 Gy); for the post-radiation recurrent patients, 3-DCRT was directly given for the recurrent lesions to the median tumor dose of 40 Gy (36-46 Gy). For patients in the study group, two cycles chemotherapy with FOLFOX4 regimen were given concurrently with radiotherapy, with the first cycle given simultaneously with the initiation of radiation and the second cycle given in the fifth week for patients receiving conventional pelvis radiation or given in the last week of 3-DCRT for patients receiving 3-DCRT directly. Another 2-4 cycles (average 3.6 cycles) sequential FOLFOX4 regimen chemotherapy were given to the patients in the study group, beginning at 2-3 wk after chemoradiation. The outcomes of symptoms relieve, tumor response, survival and toxicity were recorded and compared between the study group and the control group.. For the study group and the control group, the pain-alleviation rates were 95.2% and 91.3% (P > 0.05); the overall response rates were 56.5% and 40.0% (P > 0.05); the 1-year and 2-year survival rates were 86.9%, 50.2% and 80.0%, 23.9%, with median survival time of 25 mo and 16 mo (P < 0.05); the 2-year distant metastasis rates were 39.1% and 56.0% (P = 0.054), respectively. The side effects, except peripheral neuropathy which was relatively severer in the study group, were similar in the the two groups and well tolerated.. Three-dimensional conformal radio-therapy combined with FOLFOX4 chemotherapy for unresectable recurrent rectal cancer is a feasible and effective therapeutic approach, and can reduce distant metastasis rate and improve the survival rate.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Organoplatinum Compounds; Radiotherapy, Conformal; Rectal Neoplasms; Survival Rate

The present study compares quality of life (QoL) after neoadjuvant radiochemotherapy with or without hyperthermia in patients with advanced rectal cancer.. Between April 1994 and May 1999, 137 patients were treated by neoadjuvant radiochemotherapy with (69 patients (50.4%)) or without (68 patients (49.6%)) hyperthermia. Forty-six patients (33.6%) filled-out a 'Gastrointestinal Quality of Life Index' (GIQLI) questionnaire at four time points (before and after neoadjuvant therapy, early after surgery and after long-term follow-up) and were included in the present study.. There were no statistically significant differences in the global GIQLI index between patients treated with neoadjuvant radiochemotherapy with and without hyperthermia at any time point. The longitudinal analysis of GIQLI values in both treatment groups showed specific profiles that were identical in both treatment groups. Occurrence of severe toxicity during the neoadjuvant therapy in both arms lead to a significant temporary reduction of QoL scores at TP2 without any detrimental long-term effects. Patients with sphincter preservation and patients with sphincter resection reported similar QoL scores during long-term follow-up.. Neoadjuvant radiochemotherapy with and without hyperthermia has similar effects on the QoL of patients with locally advanced rectal cancer. The addition of hyperthermia during the neoadjuvant therapy with the potentially associated inconveniences has no negative effects on QoL.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Fluorouracil; Follow-Up Studies; Humans; Hyperthermia, Induced; Leucovorin; Longitudinal Studies; Male; Middle Aged; Neoadjuvant Therapy; Quality of Life; Radiotherapy; Rectal Neoplasms; Rectum; Severity of Illness Index; Treatment Outcome

Adjuvant chemoradiotherapy after or before resection of high-risk rectal cancer improves overall survival (OS) and pelvic control. We studied three postoperative fluorouracil (FU) radiochemotherapy regimens.. After resection of T3-4, N0, M0 or T1-4, N1, 2M0 rectal adenocarcinoma, 1,917 patients were randomly assigned to arm 1, with bolus FU in two 5-day cycles every 28 days before and after radiotherapy (XRT) plus FU via protracted venous infusion (PVI) 225 mg/m2/d during XRT; arm 2 (PVI-only arm), with PVI 42 days before and 56 days after XRT + PVI; or arm 3 (bolus-only arm), with bolus FU + leucovorin (LV) in two 5-day cycles before and after XRT, plus bolus FU + LV (levamisole was administered each cycle before and after XRT). Patients were stratified by operation type, T and N stage, and time from surgery.. Median follow-up was 5.7 years. Lethal toxicity was less than 1%, with grade 3 to 4 hematologic toxicity in 49% to 55% of the bolus arms versus 4% in the PVI arm. No disease-free survival (DFS) or OS difference was detected (3-year DFS, 67% to 69% and 3-year OS, 81% to 83% in all arms). Locoregional failure (LRF) at first relapse was 8% in arm 1, 4.6% in arm 2, and 7% in arm 3. LRF in T1-2, N1-2, and T3, N0-2 primaries who received low anterior resection (those most suitable for primary resection) was 5% in arm 1, 3% in arm 2, and 5% in arm 3.. All arms provide similar relapse-free survival and OS, with different toxicity profiles and central catheter requirements. LRF with postoperative therapy is low, justifying initial resection for T1-2, N0-2 and T3, and N0-2 anterior resection candidates.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Injections, Intravenous; Leucovorin; Levamisole; Male; Middle Aged; Neoplasm Staging; Radiotherapy, Adjuvant; Rectal Neoplasms; Survival Analysis; Treatment Outcome

The therapeutic and adverse effects of pre-operative chrono-chemoradiation with local hyperthermia for patients with rectal adenocarcinoma were evaluated.. Pre-operative radiation therapy of a total dose of 40 Gy (n = 10) or 50 Gy (n = 19) on the whole pelvis and hyperthermia once a week during the radiation therapy for 1 h were performed for patients with T2-T4 rectal adenocarcinoma. Chemotherapy consisted of 5-FU (250 mg m-2 per day) and LV (25 mg m-2 per day) administered by continuous infusion in the night for 5 days a week in the second and fourth weeks of radiation.. Grade 3+ toxicities were seen only in two patients (6.9%). A significant down staging was seen in 41.4% of all cases and 52.6% of cases with a radiation dose of 50 Gy. Of the patients who had received surgical resection of a tumour, three (11.1%) had no residue pathologically in the specimen and eight (29.6%) had microscopic lesions.. These results yielded a high response rate with minimal toxicities for advanced low-rectal adenocarcinoma. The administration of 5-FU during the sleeping time before irradiation might have an advantage not only as a chronotherapy but also as a radiation sensitizer.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Chronotherapy; Combined Modality Therapy; Female; Fluorouracil; Humans; Hyperthermia, Induced; Leucovorin; Male; Middle Aged; Rectal Neoplasms; Treatment Outcome; Vitamin B Complex

There is an argument on whether or not glutamine-supplemented parenteral nutrition is beneficial to chemotherapy in gastrointestinal neoplasm patients. The aim of this study was to prospectively evaluate the effect of parenteral nutrition with alanyl-glutamine dipeptide on gastrointestinal neoplasm patients receiving chemotherapy.. This study was a prospective, randomized double-blind clinical trial. Seventy-two patients were randomly divided into study group and control group (each group had 36 patients). The side effects during chemotherapy were observed. Serum albumin, serum pre-albumin, IgG, IgA, IgM, C3, C4 level were measured before chemotherapy and on day 4 and day 8 after chemotherapy. Nitrogen balance was also calculated simultaneously.. (1) Less side effects during chemotherapy in study group were revealed compared to those in control group (P<0.05). (2) Serum albumin and pre-albumin levels were both decreased in the two groups on day 4 after chemotherapy, and were markedly decreased in control group on day 8 after chemotherapy (P<0.05). (3) IgG, IgM, IgA levels were all decreased compared with the test results before chemotherapy on day 4 after chemotherapy in two groups, and were significantly decreased in control group on day 8 after chemotherapy (P<0.05). C3 and C4 levels were higher in study group compared with control group on day 8 after chemotherapy (P<0.05). (4) Nitrogen balance in study group was better than that in control group (P<0.05) on day 8 after chemotherapy.. Alanyl-glutamine dipeptide is beneficial to chemotherapy in gastrointestinal neoplasm patients. It could reduce the side effects of chemotherapy, which helps to improve the nutritional status, the immune function and the survival quality of patients during chemotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Complement C3; Complement C4; Dipeptides; Double-Blind Method; Female; Fluorouracil; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Leucovorin; Male; Middle Aged; Nitrogen; Parenteral Nutrition; Prealbumin; Prospective Studies; Rectal Neoplasms; Serum Albumin; Stomach Neoplasms; Young Adult

Preoperative radiotherapy is recommended for selected patients with rectal cancer. We evaluated the addition of chemotherapy to preoperative radiotherapy and the use of postoperative chemotherapy in the treatment of rectal cancer.. We randomly assigned patients with clinical stage T3 or T4 resectable rectal cancer to receive preoperative radiotherapy, preoperative chemoradiotherapy, preoperative radiotherapy and postoperative chemotherapy, or preoperative chemoradiotherapy and postoperative chemotherapy. Radiotherapy consisted of 45 Gy delivered over a period of 5 weeks. One course of chemotherapy consisted of 350 mg of fluorouracil per square meter of body-surface area per day and 20 mg of leucovorin per square meter per day, both given for 5 days. Two courses were combined with preoperative radiotherapy in the group receiving preoperative chemoradiotherapy and the group receiving preoperative chemoradiotherapy and postoperative chemotherapy; four courses were planned postoperatively in the group receiving preoperative radiotherapy and postoperative chemotherapy and the group receiving preoperative chemoradiotherapy and postoperative chemotherapy. The primary end point was overall survival.. We enrolled 1011 patients in the trial. There was no significant difference in overall survival between the groups that received chemotherapy preoperatively (P=0.84) and those that received it postoperatively (P=0.12). The combined 5-year overall survival rate for all four groups was 65.2%. The 5-year cumulative incidence rates for local recurrences were 8.7%, 9.6%, and 7.6% in the groups that received chemotherapy preoperatively, postoperatively, or both, respectively, and 17.1% in the group that did not receive chemotherapy (P=0.002). The rate of adherence to preoperative chemotherapy was 82.0%, and to postoperative chemotherapy was 42.9%.. In patients with rectal cancer who receive preoperative radiotherapy, adding fluorouracil-based chemotherapy preoperatively or postoperatively has no significant effect on survival. Chemotherapy, regardless of whether it is administered before or after surgery, confers a significant benefit with respect to local control. (ClinicalTrials.gov number, NCT00002523 [ClinicalTrials.gov].).

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Postoperative Care; Postoperative Complications; Preoperative Care; Rectal Neoplasms; Recurrence; Survival Analysis

This study was designed to determine the effect of concomitant small field boost irradiation given during preoperative chemoradiotherapy for patients with locally advanced rectal cancer.. The study prospectively enrolled 38 patients scheduled for preoperative chemoradiotherapy. Pelvic radiotherapy of 43.2 Gy/24 fractions was delivered and boost radiotherapy of 7.2 Gy/12 fractions was concomitantly administered during the latter half of the pelvic radiotherapy treatment period. Two cycles of a bolus 5-fluorouracil and leucovorin injection in the first and fifth weeks of radiotherapy were administered. The median time to surgery after completion of chemoradiotherapy was six weeks. Tumor responses to chemoradiotherapy were assessed by using magnetic resonance volumetry and post-chemoradiotherapy pathology tests to determine tumor downstaging and tumor regression rate.. Thirty-six of 38 patients (94.7 percent) underwent the scheduled surgery. The mean tumor volume reduction rate was 70.3 percent, and the clinical response rate was 66.7 percent. The downstaging rates were 41.7 percent for T classification, 85.2 percent for N classification, and 72.2 percent for stage. Tumor regression grades after preoperative chemoradiotherapy were Grade 1 in 5 patients (13.9 percent), Grade 2 in 24 patients (66.7 percent), Grade 3 in 3 patients (8.3 percent), and Grade 4 in 4 patients (11.1 percent). Ten patients (26.3 percent) experienced > or = Grade 3 acute toxicity.. Our data suggest that concomitant boost irradiation does not improve clinical outcomes compared with other published preoperative chemoradiotherapy regimens. In addition, the clinicians choosing to use concomitant small field boost irradiation should be cautious to minimize the risk of unplanned sphincter ablation.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Dose Fractionation, Radiation; Female; Fluorouracil; Humans; Injections, Intravenous; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Prospective Studies; Radiotherapy, Conformal; Rectal Neoplasms; Vitamin B Complex

In 1992, preoperative radiotherapy was considered in France as the standard treatment for T3-4 rectal cancers. The present randomized trial compares preoperative radiotherapy with chemoradiotherapy.. Patients were eligible if they presented a resectable T3-4, Nx, M0 rectal adenocarcinoma accessible to digital rectal examination. Preoperative radiotherapy with 45 Gy in 25 fractions during 5 weeks was delivered. Concurrent chemotherapy with fluorouracil 350 mg/m2/d during 5 days, together with leucovorin, was administered during the first and fifth week in the experimental arm. Surgery was planned 3 to 10 weeks after the end of radiotherapy. All patients should receive adjuvant chemotherapy with the same fluorouracil/leucovorin regimen. The primary end point of the trial was overall survival.. A total of 733 patients were eligible. Grade 3 or 4 acute toxicity was more frequent with chemoradiotherapy (14.6% v 2.7%; P < .05). There was no difference in sphincter preservation. Complete sterilization of the operative specimen was more frequent with chemoradiotherapy (11.4% v 3.6%; P < .05). The 5-year incidence of local recurrence was lower with chemoradiotherapy (8.1% v 16.5%; P < .05). Overall 5-year survival in the two groups did not differ.. Preoperative chemoradiotherapy despite a moderate increase in acute toxicity and no impact on overall survival significantly improves local control and is recommended for T3-4, N0-2, M0 adenocarcinoma of the middle and distal rectum.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Radiotherapy; Rectal Neoplasms; Recurrence; Vitamin B Complex

To evaluate the efficacy and safety of modified FOLFIRI regimen in advanced colorectal cancer (CRC) patients refractory to fluoropyrimidine and oxaliplatin.. The modified FOLFIRI regimen consisted of intravenous infusion of irinotecan 180 mg/m2 d1 + LV 200 mg/m2 dl + 5-Fu 400 mg/m2 bolus dl plus 46-hour intravenous infusion of 5-Fu 2.4 g/m2, every 2 weeks as one cycle. The main selection criterion for this study was the advanced CRC refractory to fluoropyrimidine and oxaliplatin.. Of the 80 evaluable patients for efficacy: 10 (12.5%) had a partial response, 51 (63.7%) stable disease, and 19 (23.8%) progressive disease. The median time to progression was 96 days. Safety analysis was based on the data of 83 evaluable patients. The most frequently observed grade 3 or 4 toxicities were neutropenia (24.1%), nausea/vomiting (8.4%), and diarrhea (2.4%).. Modified FOLFIRI regimen is effective and well tolerated in patients with advanced colorectal cancer refractory to fluoropyrimidine and oxaliplatin.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Diarrhea; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Nausea; Neoplasm Staging; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Prospective Studies; Pyrimidines; Rectal Neoplasms; Remission Induction; Treatment Failure

The orally bioavailable matrix metalloproteinase inhibitor MMI270 reduces tumour growth metastasis in preclinical models. We assessed the feasibility and pharmacokinetic interactions of combining MMI270 with 5-fluorouracil (5-FU) and folinic acid (FA). Entered into the study were 33 patients with advanced colorectal cancer. They received FA 200 mg/m2 over 2 h followed by 5-FU 400 mg/m2 over 15 min and 5-FU 600 mg/m2 over 22 h on days 1 and 2 of a 14-day cycle. MMI270 commenced with the second cycle at either 50 mg once daily, 150 mg three times daily or 300 mg twice daily. No dose-limiting toxicity was observed at any MMI270 dose level. Ten patients (61%) experienced joint symptoms independent of MMI270 dose, leading to interruption, modification, or discontinuation of treatment in seven patients (23%). MMI270 did not alter 5-FU pharmacokinetics. Six patients had a partial response and seven had stable disease. 5-FU/FA with MMI270 at a dose of 300 mg twice daily is well tolerated. MMI270 has no significant effect on 5-FU pharmacokinetics.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Drug Interactions; Female; Fluorouracil; Humans; Hydroxamic Acids; Leucovorin; Male; Metalloendopeptidases; Middle Aged; Protease Inhibitors; Pyrazines; Rectal Neoplasms; Sulfonamides

To evaluate the prognostic value of the posttreatment TNM stage as a predictor of outcome in locally advanced rectal cancers treated with preoperative chemotherapy and radiotherapy.. Between 1993 and 2000, 128 patients with tethered (103) or fixed (25) rectal cancers were treated with 50 Gy preoperative pelvic radiotherapy and two cycles of concurrent 5-fluorouracil infusion (20 mg/kg/d) and leucovorin (200 mg/m(2)/d) chemotherapy on Days 1-4 and 22-25 and a single bolus mitomycin C injection (8 mg/m(2)) on Day 1. Of the 128 patients, 111 had Stage T3 and 17 Stage T4 according to the rectal ultrasound or CT findings and clinical evaluation. All 128 patients underwent surgery 8 weeks after chemoradiotherapy. Postoperatively, the disease stage was determined according to the surgical and pathologic findings using the American Joint Committee on Cancer TNM staging system.. Of the 128 patients, 32 had postchemoradiotherapy (pCR) Stage 0 (T0N0M0), 37 pCR Stage I, 26 pCR Stage II, 28 pCR Stage III, and 5 pCR Stage IV disease. Of the 128 patients, 79 had pCR Stage T0-T2, 35 pCR Stage T3, and 14 pCR Stage T4. The rate of T stage downstaging was 66% (84 of 128). Of the 128 patients, 25% achieved a pathologic complete response, and 31 (24%) had positive nodal disease. Lymphovascular or perineural invasion was found in 13 patients (10%). The 5-year disease-specific survival rate was 97% for pCR Stage 0, 88% for pCR Stage I, 74% for pCR Stage II, 44% for pCR Stage III, and 0% for pCR Stage IV (p = 0.0000059). The 5-year relapse-free survival rate was 97% for pCR Stage 0, 80% for pCR Stage I, 72% for pCR Stage II, 42% for pCR Stage III, and 0% for pCR Stage IV (p < 0.000001). In univariate analysis, the pretreatment tumor status (fixed vs. tethered tumors), the pCR TNM stage, T stage downstaging, pathologic T4 tumors, node-positive disease after chemoradiotherapy, and lymphovascular or perineural invasion were statistically significant prognosticators of disease-specific survival and relapse-free survival. pCR Stage T4 disease was a strong predictor of local recurrence. The 5-year local control rate was 98% for pCR T0-T2, 89% for pCR T3, and 65% for pCR T4 disease (p = 0.00044). In multivariate analysis, the pCR TNM stage was the most statistically significant independent predictor of survival (p = 0.003) and relapse-free survival (p < 0.001).. For patients who underwent preoperative chemoradiotherapy for locally advanced rectal cancer, the pCR TNM stage was a strong prognosticator of recurrence and survival. It can be used to identify high-risk patients for additional postoperative therapy.

Topics: Adult; Aged; Antineoplastic Agents; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Mitomycin; Multivariate Analysis; Neoplasm Recurrence, Local; Neoplasm Staging; Odds Ratio; Prognosis; Radiotherapy Dosage; Rectal Neoplasms; Recurrence; Survival Rate

We evaluated the efficacy and tolerability of a modified biweekly irinotecan, 5-fluorouracil and leucovorin regimen (modified Douillard regimen) as the first-line therapy in patients with advanced colorectal cancer.. A total of 80 patients (41 male, 39 female) with recurrent or metastatic colorectal cancer were enrolled between April 2001 and December 2003. The treatment cycle consisted of irinotecan 150 mg/m(2) as a 90 min infusion on day 1, leucovorin 20 mg/m(2) intravenous bolus, immediately followed by a 48 h continuous infusion of 5-fluorouracil 3000 mg/m(2) on day 1. The primary end-point was response rate, and the secondary end-points were time to progression and toxicity profile.. An overall objective response rate of 38.7% [95% confidence interval (CI) 27.84-49.66%] was achieved. The median time to progression was 6.1 months (95% CI 4.63-7.57 months) and the median overall survival time was 20.2 months (95% CI 15.50-24.90 months). The median duration of follow-up for patients was 16.9 months. The toxicity profile was more favorable than for the conventional Douillard regimen.. We conclude that the modified Douillard regimen may be a practical and more tolerable treatment option in patients with advanced colorectal cancer.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Disease-Free Survival; Drug Administration Schedule; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Leukopenia; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Maximum Tolerated Dose; Middle Aged; Rectal Neoplasms; Survival Analysis; Treatment Outcome

The primary outcome was sphincter preservation. No benefit was found with chemoradiation. The aim of this report is to analyse postoperative complications, which were the secondary outcome.. Patients with resectable T3-4 low rectal carcinoma were randomised to receive either pre-operative 5 x 5 Gy irradiation with subsequent total mesorectal excision (TME) performed within 7 days or chemoradiation (50.4 Gy, 1.8 Gy per fraction plus bolus 5-fluorouracil and leucovorin) followed by TME after 4-6 weeks.. Three hundred and five patients (153 in 5 x 5 Gy group and 152 in chemoradiation group) were analysed. The rates of patients with postoperative complications for the 5 x 5 Gy group and for the chemoradiation group were 27 vs 21%, respectively (P = 0.27). If the values were expressed in terms of number of complications, the rates were 31 vs 22%, respectively (P = 0.06). The corresponding values for severe complications were 10 vs 11% (P = 0.85) of patients with complications and 12 vs 11% (P = 0.85) of events.. The study did not demonstrate a statistically significant difference in the rate of postoperative complications after short-course pre-operative radiotherapy compared with full course chemoradiation.

Topics: Antineoplastic Agents; Colectomy; Fluorouracil; Humans; Leucovorin; Neoadjuvant Therapy; Postoperative Complications; Preoperative Care; Radiotherapy, Adjuvant; Rectal Neoplasms; Treatment Outcome

Seventy-two patients suffering from a metastatic colorectal cancer received, as first line treatment, a combination chronotherapy with 5-FU and folinic acid (infused from 10 pm to 10 am with a peak at 4 am, respectively at doses of 700 and 300 mg/m2 per day) and carboplatin (infused at the dose of 40 mg/m2 per day from 10 am to 10 pm with a peak at 4 pm). The courses of four days were repeated every two weeks. A major tumoral response was observed in 60% cases (68% in those not previously treated with adjuvant chemotherapy). The median times to progression and overall survival established at 11 and 27 months. The clinical (grades 3-4 in maximum 5% cases) and hematological (grades 3-4 in maximum 10-29% cases) toxicities were quite limited. Our observations suggest the interest to incorporate carboplatin in the combined infusional treatment of colorectal cancer.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Chronobiology Phenomena; Colonic Neoplasms; Colorectal Neoplasms; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Rectal Neoplasms; Survival Analysis

A randomized controlled trial was started in Japan to evaluate whether laparoscopic surgery is the optimal treatment for colorectal cancer. Patients with T3 or deeper carcinoma in the colorectum without transverse and descending colons are pre-operatively randomized to either open or laparoscopic colorectal resection. Surgeons in 24 specialized institutions will recruit 818 patients. The primary end-point is overall survival. Secondary end-points are relapse-free survival, short-term clinical outcome, adverse events, the proportion of conversion from laparoscopic surgery to open surgery, and the proportion of completion of laparoscopic surgery.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colonic Neoplasms; Colorectal Neoplasms; Disease-Free Survival; Drug Administration Schedule; Endpoint Determination; Fluorouracil; Humans; Laparoscopy; Leucovorin; Lymph Node Excision; Middle Aged; Rectal Neoplasms; Sigmoid Neoplasms; Survival Rate; Treatment Outcome

The European Organisation for Research and Treatment of Cancer (EORTC) trial evaluated the addition of chemotherapy (CT) to preoperative radiation (preop RT) and the value of postoperative CT for improving the survival in patients with T3-4 resectable rectal cancer. Patients were allocated to the following four arms: arm 1, preop RT 45 Gy in 5 weeks; arm 2, preop RT plus two 5-day CT courses (fluorouracil 350 mg/m2/d and leucovorin 20 mg/m2/d) in the first and fifth week of RT; arm 3, preop RT plus four postoperative CT courses; and arm 4, preop RT and CT plus postoperative CT. We investigated the effect of adding CT on the pathologic parameters.. One thousand eleven patients were entered onto the trial; 505 received preop RT (arms 1 and 3), and 506 received preop RT-CT (arms 2 and 4). We analyzed the differences in tumor size, tumor node stage, number of retrieved nodes, and histologic features such as lymphatic, venous, and perineural invasions, tumor differentiation, and tumor type.. After preop RT-CT, tumors were smaller (P < .0001), had less advanced pT (P < .001) and pN stages (P < .001), had small numbers of examined nodes (P = .046), and less frequent LVN invasions (P < or = .008). Mucinous tumors increased after preop RT-CT (P < .001).. In patients with rectal cancer, preliminary results of EORTC Trial 22921 indicate that the addition of CT to preop RT induces down-sizing, downstaging, and significant changes in histologic characteristics. Longer follow-up is needed to assess the impact on local control and survival.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chi-Square Distribution; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Preoperative Care; Prospective Studies; Radiotherapy Dosage; Rectal Neoplasms; Statistics, Nonparametric; Treatment Outcome

A phase I trial of preoperative high dose pelvic radiotherapy and oral UFT/l-leucovorin in patients with locally advanced and unresectable rectal cancer patients to evaluate toxicity and efficacy was performed. Eighteen patients (14 with primary unresectable tumours and four with locally recurrent tumours) were treated. All patients were evaluable for acute toxicity and efficacy. Patients received increasing doses of UFT (150 to 300 mg/m2/day UFT and a fixed dose of 22.5 mg/day l-leucovorin) with each fraction, five days a week for 30 days, concomitantly with pelvic radiotherapy (60 Gy in 30 fractions using concomitant boost technique). All patients received the planned dose of radiotherapy. No hematological toxicity was observed. Only one patient developed grade 3 toxicity (diarrhea). Fourteen patients (78%) had surgery (11 R0 and 3 R1) after median 40 days. Two patients (11%) had a complete pathological response. Ten patients are alive after median follow-up of 49 months. Toxicity, resection rate and survival are very encouraging and the study continues as a phase II trial.

Topics: Adenocarcinoma; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cohort Studies; Diarrhea; Feasibility Studies; Female; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Radiotherapy Dosage; Rectal Neoplasms; Remission Induction; Survival Rate; Tegafur; Treatment Outcome; Uracil

A clinical study has been conducted since August 2001 to investigate whether chemotherapy with CPT-11/l-LV/ 5-FU/UFT could be an effective regimen for advanced or recurrent colorectal cancer. The chemotherapy consisted of CPT-11 30 mg/m2 iv, as a 120-minute infusion, followed by l-LV 30 mg/m2, as a 60-minute infusion, followed by 5-FU 300 mg/m2, as a 120-minute infusion. This treatment was administered weekly for 6 weeks followed by a 2-week rest period and repeated every 8 weeks. UFT (250 mg/m2/day) was orally administered daily. All patients were evaluable for efficacy, 2 CR, 5 PR, 3 SD and 7 PD. The overall response rate was 41.1% with a median time to progression of 7.1 months and a median survival time of 12.0 months. No grade 3/4 toxicities were observed. The present study suggests that combination chemotherapy with CPT-11, l-LV, 5-FU, and UFT is well tolerated and might be a promising regimen for advanced or recurrent colorectal cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Drug Administration Schedule; Drug Combinations; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Male; Middle Aged; Nausea; Rectal Neoplasms; Survival Rate; Tegafur; Uracil; Vomiting, Anticipatory

The purpose of this study was to evaluate the maximum tolerated dose (MTD) and recommended dose of oxaliplatin given synchronously with 5-fluorouracil (5FU), leucovorin (LV) and preoperative pelvic radiation for primary unresectable, locally advanced, rectal cancer. Preoperative pelvic radiotherapy using a three- or four-field technique and megavoltage photons comprised 45 Gy given in 25 fractions, 1.8 Gy per fraction, and delivered with escalating doses of oxaliplatin in combination with low-dose LV and 5FU. Chemotherapy was given synchronously with radiotherapy in weeks 1 and 5. Escalating doses of oxaliplatin (85, 130 and 150 mg m(-2)) were given on days 2 and 30, followed by low-dose LV (20 mg m(-2)) and 5FU (350 mg m(-2)), both given on days 1-5 and 29-33. Surgery was performed 6-10 weeks later. The MTD was determined as the dose causing more than a third of patients to have a dose-limiting toxicity (DLT). Once the MTD was reached, a further 14 patients were treated at the dose level below the MTD. In all, 32 patients received oxaliplatin at the three dose levels, median age 60 years (range 31-79), 24 males and eight females. The MTD was reached at 150 mg m(-2) when four out of six patients experienced DLT. Dose-limiting grade 3 or 4 diarrhoea was reported in two out of six patients at 85 mg m(-2), 5 out of 20 at 130 mg m(-2) and four out of 6 at 150 mg m(-2). Grade 3 neuropathy was reported at 130 mg m(-2) (1 out of 20) and at 150 mg m(-2) (two out of six), and serious haematological toxicity was minimal; one grade 3 anaemia at 150 mg m(-2). In all, 28 out of 32 patients completed all treatments as planned; three had radiotherapy interrupted and three a chemotherapy dose reduction. Four patients did not proceed to surgery due to the presence of metastatic disease (two), unfitness (one) or patient refusal (one). Also, 28 patients underwent surgical resection. Histopathology demonstrated histopathological complete response (pCR) 2 out of 27 (7%), Tmic 3 out of 27 (11%), pCR+Tmic 5 out of 27 (19%), pT0-2 6 out of 27 (22%) and histologically confirmed clear circumferential resection margins in 22 out of 27 (81%). Dose-limiting toxicity with oxaliplatin is 150 mg m(-2) given days 2 and 30 when added to the described 5FU LV and 45 Gy radiation preoperatively. The acceptable toxicity and compliance at 130 mg m(-2) recommend testing this dose in future phase II studies. The tumour downstaging and complete resection rates are encouragingly high for this very

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Pelvis; Radiotherapy, High-Energy; Rectal Neoplasms; Treatment Outcome

For patients with rectal cancer treated with full thickness local excision the risk of mesorectal nodal metastases has to be very low. The aim was to assess this risk after preoperative radiotherapy in relation to pathological T-category.. Three hundred sixteen patients with resectable cT3-4 low rectal carcinoma were randomised to receive either pre-operative 5 x 5 Gy irradiation with subsequent surgery performed within 7 days or chemoradiation (50.4, 1.8 Gy per fraction plus bolus 5-fluorouracil and leucovorin) followed by surgery after 4-6 weeks. The pathological reports of patients who fulfilled entry criteria and had preoperative irradiation followed by transabdominal surgery were analysed.. Significant downstaging of primary tumour (P<0.001) and of nodal disease (P=0.007) was observed after chemoradiation in comparison with short-course irradiation. In chemoradiation group, for patients with complete pathological response and for ypT1 category, the rate of nodal metastases was low - 5% (95% confidence interval [CI] 0-14%) and 8% (95% CI 0-24%), respectively. The rate of ypN-positive disease in chemoradiation group was similar to that recorded in short-course irradiation group for ypT2 category 26% (95% CI 14-38%) vs. 28% (95% CI 16-40%), P=0.83 and for ypT3-4 category 55% (95% CI 41-69%) vs. 64% (95% CI 54-74%), respectively, P=0.37. For ypT2 category after chemoradiation, the rate of nodal disease remained high even in subgroup with low residual cancer cells density (20%, 95% CI 4-36%).. For patients with tumours downstaged by chemoradiation to ypT0 and ypT1 full thickness local excision may be considered as an acceptable approach, because the risk of mesorectal lymph nodes metastases is low. The selection criteria for preoperative radio(chemo)therapy and local excision are discussed.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Combined Modality Therapy; Fluorouracil; Humans; Leucovorin; Lymphatic Metastasis; Neoadjuvant Therapy; Neoplasm Staging; Prognosis; Rectal Neoplasms; Risk Factors; Treatment Outcome

The European Organisation for Research and Treatment of Cancer (EORTC) 22921 four-arm randomised trial questioned the value of preoperative chemoradiation (XRT-CT) versus preoperative radiation (XRT) and the value of additional postoperative chemotherapy (CT) versus none in T3-T4 M0 resectable rectal cancer patients. We report on the preoperative toxicity, treatment compliance and early deaths (all deaths up to 30 days after surgery) of the two treatment modalities in patients who were entered into trial before January 2001. In the XRT Group (group A), patients received 45 Gy, 25 fractions over 5 weeks. In the XRT-CT Group (group B), two 5-day courses of CT were added to the first and fifth weeks of XRT. For each CT course: 5-fluorouracil (5-FU) 350 mg/m2/day and Leucovorin (LV) 20 mg/m2/day were given. 398 and 400 patients started treatment in groups A and B, respectively. Grade 2+acute diarrhoea occurred in 17.3 and 34.3% of patients in groups A and B, respectively (P<0.005). The other side-effects remained unchanged or were only marginally increased. The compliance with RT was 98.5 and 95.5% in groups A and B, respectively. In group B, 78.7 and 71.1% of the patients received 95-105% of the planned CT doses at the first and second courses, respectively. 6 patients died preoperatively, 2 from toxicity in group B. 8 patients (1%) died within the 30 days after surgery in both groups. At the doses recommended in the protocol, the addition of 5-FU-LV to preoperative XRT slightly increased the amount of acute toxicity. However, the compliance with the radiation protocol or the feasibility of surgery did not decrease.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Patient Compliance; Prognosis; Radiotherapy Dosage; Rectal Neoplasms

The purpose of our study was to determine the maximum-tolerated dose, dose-limiting toxicity, safety profile, and pharmacokinetics of the polyamine synthesis inhibitor SAM486A given in combination with 5-fluorouracil/leucovorin (5-FU/LV) in cancer patients.. Patients with advanced colorectal cancer were treated with 5-FU [bolus (400 mg/m(2)) followed by a 22-h infusion (600 mg/m(2))] and LV (200 mg/m(2)) and escalating doses of SAM486A, 1-3-h infusion daily for 3 days. Plasma sampling was performed to characterize the pharmacokinetics and pharmacodynamics of the combination. Twenty-seven patients with metastatic colorectal cancer and 1 with pseudomyxoma peritonei were treated. Twenty-six patients received SAM486A in the combination at doses ranging from 25 to 150 mg/m(2)/day. Dose-limiting toxicity consisting of fatigue grade 3 was seen at 150 mg/m(2)/day. Other adverse events included neutropenia, hand and foot syndrome, nausea, vomiting, diarrhea, and constipation. Fifteen of 26 patients evaluable for best response according to the Southwest Oncology Group criteria achieved a partial response [8 (30%) of 26] or stable disease [9 (35%) of 26]. SAM486A did not influence the pharmacokinetics of 5-FU, and SAM486A clearance was similar to that when used as a single agent.. The novel molecular agent SAM486A is tolerable and safe in combination with a standard 5-FU regimen in patients with advanced colorectal cancer. The dose of SAM486A recommended for additional studies with this combination is 125 mg/m(2)/day. A disease-directed evaluation of SAM486A using this regimen is warranted.

Topics: Adult; Aged; Amidines; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Colorectal Neoplasms; Female; Fluorouracil; Humans; Indans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Pseudomyxoma Peritonei; Rectal Neoplasms; Treatment Outcome

To determine the maximal tolerated dose of chronomodulated 5-fluorouracil (5-FU) and leucovorin (LV) given concurrently with radiotherapy in patients with rectal cancer.. Forty-five patients with T3, T4 or recurrent rectal cancer received concurrent radiotherapy to a minimal dose of 4500 cGy. Chemotherapy was administered by a programmable pump in chronomodulated fashion, with 62.5% of the total dose given within 7 hours around 9:30 pm. The starting doses were LV at 5 mg/m2/d and 5-FU at 150 mg/m2/d. LV was escalated in 5-mg/m2 increments to 20 mg/m2/d; 5-FU was then escalated in 25 mg/m2 increments to the maximal tolerated dose.. Diarrhea and stomatitis were dose limiting, with Grade 3 or worse toxicity occurring in 16% and 5% of patients, respectively. Thirty-seven patients (84%) received their scheduled dose of radiotherapy (range, 4500-6000 cGy). Thirty-two patients had clinical T3 disease; all were treated with definitive surgery; 23 (71%) underwent sphincter-sparing surgery with complete resection in 28 (87%). Ten patients (31%) had no evidence of tumor in the pathologic specimen.. Preoperative chemoradiotherapy in rectal cancer using chronomodulated 5-FU and LV is feasible. The recommended Phase II dose is 5-FU 200 mg/m2 and LV 20 mg/m2 daily for 5 weeks.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Chronotherapy; Combined Modality Therapy; Diarrhea; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Male; Maximum Tolerated Dose; Middle Aged; Patient Compliance; Radiotherapy Dosage; Rectal Neoplasms; Stomatitis

Preoperative radiochemotherapy (RCT) followed by curative surgery is a well-accepted therapeutic option in the treatment of advanced rectal cancer. Usually, the anal sphincter is located in the irradiation area of a preoperative RCT regime. The aim of this study is to evaluate the influence of preoperative RCT on anal sphincter function.. Between 1994 and 2000, 102 patients with rectal cancer stage uT3/uT4 were analyzed. All patients underwent radiotherapy with 45 Gy (5 x 1.8 Gy) including two cycles of 5-fluorouracil (5-FU)/leucovorin (folinic acid) chemotherapy. 46 patients were treated additionally with up to five sessions of locoregional hyperthermia. The sphincter function was analyzed by perfusion manometry before preoperative therapy and 4 weeks after pretreatment had been finished. For statistics, the Wilcoxon signed rank test and Mann-Whitney U-test were used (SPSS 9.0 for Windows((R))).. The mean value of all 102 patients showed a significant reduction of the mean maximum resting pressure from 97 to 89 mmHg (p = 0.02). For the mean maximal squeeze pressure no significant difference could be shown (178 vs. 176 mmHg). For patients with distal (

Topics: Anal Canal; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Fluorouracil; Humans; Hyperthermia, Induced; International Cooperation; Leucovorin; Male; Manometry; Middle Aged; Preoperative Care; Rectal Neoplasms; Treatment Outcome

The aim of this study was to evaluate the efficacy and toxicity of 5-fluorouracil (5-FU) and l-leucovorin (l-LV) given at the same dose intensity and administered monthly (given weekly for 3 weeks followed by a week of rest; arm A) or every 2 months (given weekly for 6 weeks followed by 2 weeks rest; arm B) to patients with advanced colorectal carcinoma. The dose of 5-FU was 500 mg/body or 750 mg/body, with an average dose of 432.8 mg/m2. A total of 7 institutions participated in this multi-center study and were randomly divided into 2 groups of arms A and B. Thirty-three patients were entered into arm A and 21 into B. The overall response rate was significantly (p = 0.007) greater in arm B (23.5%) than in arm A (0%). The most frequently observed toxicity was diarrhea, which was observed in 6.5% of arm A and in 33.3% of arm B, marking a significant difference (p = 0.034). These data suggest that a monthly 5-FU/l-LV regimen might be less toxic than a 2-months regimen and less effective at the dose given as above. Further study is needed to evaluate the efficacy of a monthly regimen.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Case-Control Studies; Colonic Neoplasms; Diarrhea; Drug Administration Schedule; Female; Fluorouracil; Gastrointestinal Diseases; Humans; Leucovorin; Male; Middle Aged; Prospective Studies; Rectal Neoplasms; Remission Induction; Survival Rate

The aim of this study was to evaluate the feasibility and toxicity of a novel hyperthermic chemotherapy approach for patients with locally recurrent adenocarcinoma of the rectum. All patients were pre-irradiated (> or = 45 Gy) and had histologically proven pelvic recurrence. Hyperthermic chemotherapy was applied according to a modified 'OFF'-schedule with weekly infusions of 43 mg/m2 of oxaliplatin (i.v., 120 min), 500 mg/m2 of folinic acid (i.v., 120 min) and 2.6 g/m2 of continuous infusional 5-fluorouracil (24 h) for 6 consecutive weeks. Oxaliplatin was started in parallel to pelvic radiofrequency hyperthermia that was provided by the BSD 2000-system. A total of 67 applications were administered to nine patients and were well tolerated. A total of 55/67 (82%) chemotherapy courses were applied without dose-reduction. In 62/67 (93%) hyperthermia sessions, a treatment time of > 60 min was maintained. Tolerated power levels were on average 600 W and, thus, slightly lower than those described in curative pelvic hyperthermia schedules. Eight out of 10 episodes of severe (WHO III degrees) toxicity represented typical side-effects of the chemotherapy given (nausea n = 4, diarrhoea n = 3, neuropathy n = 1). Two severe adverse events were firstly attributable to hyperthermia (haematuria, n = 1; deterioration of a decubital ulcer, n = 1). No patient suffered WHO-disease progression during the treatment period. Two patients achieved a partial remission. It is concluded that hyperthermic chemotherapy with oxaliplatin, folinic acid and 5-FU is feasible on an outpatient basis. Overall toxicity was moderate, although hyperthermia may add side-effects to this approach. Results, moreover, suggest a relevant palliative effect in patients with pre-irradiated pelvic recurrence of rectal cancer.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Fluorouracil; Humans; Hyperthermia, Induced; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Organoplatinum Compounds; Oxaliplatin; Pelvic Neoplasms; Rectal Neoplasms; Survival Rate; Treatment Outcome

To assess tolerance and efficacy of preoperative treatment with uracil/tegafur and radiotherapy (RT) followed by surgery and postoperative flurouracil (FU)/leucovorin (LV) in patients with rectal cancer.. Patients (n = 94) with potentially resectable tumors, ultrasound at stages T2N+ (n = 4), T3 (n = 77), T4 (n = 13) were treated with UFT (400 mg/m2/d, 5 days a week for 5 weeks) and concomitant RT to the pelvis (45 Gy; 1.8 Gy/d over 5 weeks). Patients underwent surgery 5 to 6 weeks later followed by four cycles of FU/LV. Primary end points included downstaging, pathologic responses, and sphincter-preserving surgery. Secondary end points were recurrence-free survival and overall survival.. All patients received the full RT dose. Fifteen patients (16%) needed UFT dose reduction. Preoperative G3+ toxicities included diarrhea (14%), leukopenia (1%), thrombocytopenia (1%), and nausea (4%). The downstaging rate was 54%, pathologic complete response (pCR) was 9% and, in an additional 23%, there were only residual microscopic foci. When cellular viability criteria were taken into account, the pCR was 15%. From 43 patients with abdominoperineal resection indication, 11 (25%) had sphincter-preserving surgery performed. Postoperative scheduled chemotherapy dose was not administered to 24% of patients because of G3+ toxicity (diarrhea, 8%; mucositis, 9%; and leukopenia, 7%). Patients with downstaging had significantly higher survival and recurrence-free survival rates than those without. At 3 years, actuarial patterns of failure were pelvic, 5% and distant, 11%. OS was 75%.. UFT combined with RT is safe and effective. In resectable rectal cancer, if preoperative treatment is considered, this approach can be an option.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Disease-Free Survival; Female; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Postoperative Period; Preoperative Care; Rectal Neoplasms; Tegafur; Uracil

The aim was to verify whether preoperative conventionally fractionated chemoradiation offers an advantage in sphincter preservation in comparison with preoperative short-term irradiation.. Patients with resectable T3-4 rectal carcinoma without sphincters' infiltration and with a lesion accessible to digital rectal examination were randomised into: preoperative 5x5Gy short-term irradiation with subsequent total mesorectal excision (TME) performed within 7 days or chemoradiation to a total dose of 50.4Gy (1.8Gy per fraction) concomitantly with two courses of bolus 5-fluorouracil and leucovorin followed by TME after 4-6 weeks. Surgeons were obliged to base the type of operation on the tumour status at the time of surgery.. Between 1999 and 2002, 316 patients from 19 institutions were enrolled. The sphincter preservation rate was 61% in the 5x5Gy arm and 58% in the radiochemotherapy arm, P = 0.57. The tumour was on average 1.9 cm smaller (P < 0.001) among patients treated with chemoradiation compared with short-term schedule. For patients who underwent sphincter-preserving procedure, the surgeons generally followed the rule of tailoring the resection according to tumour downsizing; the median distal bowel margin was identical (2 cm) for both randomised groups. However, in the chemoradiation group, five patients underwent abdominoperineal resection despite clinical complete response.. Despite significant downsizing, chemoradiation did not result in increased sphincter preservation rate in comparison with short-term preoperative radiotherapy. The surgeons' decisions were subjective and based on pre-treatment tumour volume at least in clinical complete responders.

Topics: Adult; Aged; Anal Canal; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Dose Fractionation, Radiation; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Invasiveness; Rectal Neoplasms; Treatment Outcome

The aim of this study was to evaluate the effectiveness of 6-month therapy with leucovorin (LV) + 5-fluorouracil (5-FU) vs 12 months of therapy with levamisole (LVZ) + 5-FU, as adjuvant chemotherapy in patients with completely resected Dukes' stage B2 or C rectal cancer. One hundred and fifty patients with surgically resected rectal carcinoma, were enrolled in the present study; Dukes' stage B2 (n=70) or C (n=80), were randomly assigned to chemotherapy with 5-FU + LV x 6 months or 5-FU + LVZ x 12 months. Patient characteristics were equally balanced between the examined groups. Adjuvant CT consisted of LV 20 mg/m(2) intravenously (i.v.) plus 5-FU 450 mg/m(2) i.v., on days 1-5 every 4 weeks for 6 cycles or 5-FU 450 mg/m(2) i.v. every week plus LVZ 50 mg t.i.d x 3 days for 1 year. All patients received radiotherapy with a three-field technique to a total dose of 45 Gy, over 5 weeks. After a median follow-up of 7.4 years there were no significant differences between the two treatment groups with respect to the recurrence rates (P=0.821). Moreover, there was no difference in disease-free survival for patients stage Dukes' B2 (log-rank p=0.73); median for LV group 90 (8-131) months, and for LVZ group 86.5 (3-129) months. No difference was noted in disease-free survival for patients stage Dukes' C (log-rank p=0.73); median for LV group 60 (17-128) months, and for LVZ group 64 (2-123) months. There was no difference in overall survival for patients stage Dukes' B2 (log-rank p=0.75); median for LV group 90 (22-131) months, and for LVZ group 86 (10-129) months. For stage Dukes' C (log-rank p=0.73); median for LV group 67 (17-128) months, and for LVZ group 64 (5-123) months. Toxicities were as follows in the 5-FU + LVZ vs 5-FU + LV group; myelosuppression (leucopenia grade 3, 12% vs 4%, p<0.04), diarrhea (grade 0, 60% vs 76%, p<0.02), and liver toxicity (increase of transaminases >3-fold, 12 patients vs 2, p<0.03), were more frequent in LVZ group. None of the patients stopped chemotherapy because of the toxicity, and there were no toxicity-related deaths. In conclusion, adjuvant chemotherapy in RC with LV + 5-FU for 6 months is equally effective and less toxic than LVZ + 5-FU for 12 months.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Female; Fluorouracil; Humans; Leucovorin; Levamisole; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Rectal Neoplasms; Survival Rate; Treatment Outcome

Preoperative radiotherapy is standard treatment for rectal cancer and is often combined with 5-fluorouracil-based chemotherapy. UFT, a new oral 5FU derivative, given daily during a course of radiotherapy mimics the effect of continuous-infusion 5FU.. To determine the maximum tolerated dose of oral UFT and leucovorin with preoperative pelvic irradiation for rectal cancer, and assess tumor response.. In this phase 1 trial, 16 patients aged 42-79 years with tumors within 12 cm of the anal verge received radiotherapy, 45 Gy over 5 weeks, an escalating dose of oral UFT, and a fixed dose of 30 mg/day leucovorin. UFT and leucovorin were given for 28 consecutive days concomitant with the first 4 weeks of radiotherapy. Surgery was scheduled for 4-6 weeks after completion of radiotherapy. The surgical procedure was determined by the surgeon at the time of surgery.. No grade III toxicity was seen at 200 mg/m2/day UFT. Of eight patients who received 240 mg/m2/day UFT, one developed grade IV diarrhea; of four patients who received 270 mg/m2/day UFT, one was hospitalized with grade IV diarrhea and leukopenic fever and died during hospitalization. Of the 15 evaluable patients, 9 had pathologic tumor downstaging including 4 patients with complete response. Only one patient required a colostomy.. The MTD of UFT together with leucovorin and preoperative radiotherapy for rectal cancer is 240 mg/m2. The major toxicity was diarrhea. Downstaging was noted in 60% of patients, allowing sphincter-preserving surgery even in patients with low tumors.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colectomy; Combined Modality Therapy; Female; Folic Acid; Humans; Leucovorin; Male; Maximum Tolerated Dose; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Radiotherapy; Rectal Neoplasms; Tegafur; Treatment Outcome; Ultrasonography; Uracil

The aim of this study was to determine whether the efficacy of the combination of 5-fluorouracil (5-FU), leucovorin (LV) and radiation therapy (RT) could be improved by the addition of interferon-alpha2b (IFN-alpha) in patients who have had a 'curative' resection, for rectal adenocarcinoma (Dukes' B2/C; T3 N0, T4 N0, N1-3).. A total of 207 eligible patients with a performance status of 0 or 1 were randomized postoperatively between days 21 and 70 to one of the two treatment groups: group A, LV 20 mg/m2 i.v. bolus and 5-FU 425 mg/m2 i.v. days 1-5 and 29-33, LV 20 mg/m2 and 5-FU 400 mg/m2 days 57-60 and 85-88, LV 20 mg/m2 and 5-FU 380 mg/m2 days 1-5 and 29-33 with the second day 1 occurring 28 days after the completion of RT (45 Gy); group B, LV, 5-FU and RT as in group A, and IFN-alpha 5 x 10(6) IU s.c. three times during each week chemotherapy is given.. 104 patients were randomized into group A and 103 into group B. There was no statistically significant difference in either disease-free survival or overall survival between the two groups. Toxicity was also the same, except for the flu-like syndrome associated with the IFN-alpha administration.. There was no difference in efficacy between the two combinations. Toxicity was greater with the LV + 5-FU + IFN-alpha regimen because of the flu-like syndrome.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Disease-Free Survival; Female; Fluorouracil; Humans; Infusions, Intravenous; Injections, Intravenous; Interferon alpha-2; Interferon-alpha; Leucovorin; Male; Middle Aged; Radiotherapy, Adjuvant; Recombinant Proteins; Rectal Neoplasms; Treatment Outcome

The combination of radiation, fluorouracil, and oxaliplatin in locally advanced rectal cancer has been shown to be feasible in a phase I trial. The purpose of this phase II trial was to assess tolerance and efficacy of this regimen in a preoperative setting.. Between May 2000 and October 2001, 40 operable patients were entered onto the study. Radiotherapy was delivered with a three-field technique to a dose of 50 Gy over 5 weeks with a concomitant boost approach. Two cycles of chemotherapy were given synchronously on weeks 1 and 5, with oxaliplatin 130 mg/m(2) on day 1 followed by 5-day continuous infusion of fluorouracil 350 mg/m(2) and L-folinic acid 100 mg/m(2). Surgery was planned 5 weeks later.. All patients completed treatment without modification except one who experienced grade 3/4 toxicity. Grade 3 toxicity was seen in seven patients. Surgery was performed in all patients after a mean interval time of 5 weeks. An objective clinical response was seen in 30 patients (75%). Sphincter-saving surgery was possible in 26 patients. No postoperative deaths occurred. In four patients (10%), a reoperation was necessary (anastomotic fistula, n = 2; pelvic abscess, n = 2). In six cases the operative specimen was sterilized (15%), and in 12 cases (30%), only few residual cells were detected.. Such a combined preoperative chemoradiotherapy and oxaliplatin-containing regimen is well tolerated with no increase in surgical toxicity. The good response rate observed warrants its use in further clinical trials.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaliplatin; Radiotherapy Dosage; Radiotherapy, Adjuvant; Rectal Neoplasms; Treatment Outcome

To evaluate the efficacy and safety of irinotecan as second-line treatment in patients with advanced colorectal cancer (ACC) failing or relapsing after 5-fluorouracil (5-FU) plus leucovorin (LV) standard chemotherapy.. Irinotecan was randomly administered in two different schedules (once every 3 weeks, and every 10 days) in patients failing prior 5-FU plus LV. Patients were randomized to two treatment groups: group A received irinotecan 350 mg/m2 every 21 days and group B received irinotecan 175 mg/m2 days 1 and 10 every 21 days.. Group A comprised 60 patients: 34 male/26 female, median age 64 years (range 48-70 years), and median Karnofsky performance status (PS) 90. Their metastatic sites included liver (n=47), lymph nodes (n=27), lung (n=14), abdomen (n=14), pelvis (n=8), "other" (n=2), and local recurrence (n=12). Group B comprised 60 patients: 36 male/24 female, median age 62 years (46-70 years), and median PS 90. Their metastatic sites included liver (n=49), lymph nodes (n=29), lung (n=17), abdomen (n=16), pelvis (n=11), "other" (n=2), and local recurrence (n=13). Group A showed the following responses: complete response (CR) 2, partial response (PR) 12, stable disease (SD) 21, progressive disease (PD) 26, overall response rate (ORR) 23%, tumor growth control 58%. Group B showed the following responses: CR 1, PR 14, SD 22, PD 23; ORR 25%; tumor growth control 62%. Toxicities included acute cholinergic syndrome (group A 53%, group B 19%; P<0.0001), late-onset diarrhea grade 1/2 (group A 21%, group B 46%) and grade 3/4 (group A 41%, group B 66%; P<0.0001), nausea and vomiting grade 1/2 (group A 34%, group B 59%) and grade 3/4 (group A 30%, group B 12%; P<0.0001), neutropenia grade 3/4 (group A 27%, group B 28%; P<0.03), with febrile neutropenia seen in only four patients in group A, anemia grade more than 2 (group A 28%, group B 12%; P<0.05), asthenia grade more than 3 (group A 24%, group B 18%; P<0.001), and alopecia grade more than 3 (group A 40%, group B 34%; P<0.2).. . The present study indicates that, in patients with ACC who have relapsed after 5-FU plus LV, the administration of irinotecan fractionated into two doses every 21 days yields a similar efficacy to, but a much lower incidence of toxicity than, the same total dose of irinotecan administered once every 21 days.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Colorectal Neoplasms; Disease Progression; Disease-Free Survival; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Irinotecan; Karnofsky Performance Status; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Rectal Neoplasms; Topoisomerase I Inhibitors

Oxaliplatin (OXA)/5-fluorouracil (5-FU) have confirmed their preclinical synergy in advanced colorectal cancer patients. Chemoradiotherapy with 5-FU + leucovorin (LV) is considered the standard treatment in unresectable rectal cancer patients. The objective was to evaluate OXA with 5-FU + LV and concurrent radiotherapy in unresectable rectal cancer patients.. OXA 25 mg/m(2)/day in 30-min infusions, followed by bolus LV 20 mg/m(2)/day and bolus 5-FU 375 mg/m(2)/day. All drugs were given on 4 days during Weeks 1 and 5 of a standard radiotherapy cycle (50.4 Gy). A single OXA dose (50 mg/m(2)) was also given on the third week of radiotherapy. A cycle of OXA with 5-FU + LV was administered 4 weeks after chemoradiotherapy, with surgery planned 4 weeks later.. Between March 1998 and April 2000, 22 patients with T3-T4 unresectable rectal cancer were accrued. Patient characteristics included the following: 11 females, 11 males, median age 58 (range: 18-76). Performance status ECOG (PS) 0: 2 patients, PS 1: 7 patients, and PS 2: 13 patients. The following RTOG Grade 3-4 toxicities were reported: diarrhea, 6 patients; cutaneous, 3 patients; neutropenia-leukopenia, 2 patients; and thrombocytopenia, 1 patient; 1 treatment-related death resulted (febrile neutropenia-sepsis after chemoradiotherapy). Only 1 patient had neurosensory Grade 2 (OXA-specific Levi's scale) toxicity. Nine patients had PS worsening during treatment. Five patients had chemoradiotherapy delay (median: 6 days). Of 22 patients, 16 underwent surgery (without serious surgical complications); 12/16 had a complete resection (5/12 had sphincter preservation). Pathologic examination revealed 3/12 complete remissions, 2/12 minimal microscopic residual disease, 2/12 T2N0, 1/12 T3N0, and 4/12 positive nodes; 4/16 had unresectable disease. Median follow-up was 15 months (range: 3.0-43.4 months), median time to progression was 15.7 months (CI 95%, 0, 31.7), and median overall survival was 19.5 months (CI 95%, 18.0, 21).. Outpatient treatment with low-dose, 30-min daily OXA infusion was feasible and very active, with acceptable toxicity.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Drug Administration Schedule; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Prognosis; Rectal Neoplasms

The aim of this study was to evaluate the efficacy of preoperative radiation therapy for resectable rectal adenocarcinoma (T3-T4) when delivered in combination with chemotherapy (oral tegafur-uracil modulated with leucovorin).. Thirty-eight patients (23 males; mean age, 62 years.) with histologically proven rectal adenocarcinoma with primary tumor clinical classification T3-T4 (resectable) and N0 or N1-N2, according to TNM staging system, took part in the present clinical trial. After tumor and metastasis resectability confirmation, radiation therapy was administered by delivering a dose of 45 Gy in 25 fractions for 5 weeks. Chemotherapy treatment was initiated on the same day as radiotherapy and consisted of intravenous infusion of 6S-steroisomer of leucovorin 250 mg/m /day in 2 hours on Day 1, followed by oral 350 or 300 mg/m /day of tegafur (a 5-fluorouracil prodrug) plus uracil on Days 1 to 14 divided into 2 daily doses, and oral 6S-steroisomer of leucovorin 7.5 mg/12 hours on Days 2 to 14, with a total of 102 courses of neoadjuvant chemotherapy (, mean of 2.7 courses per patient). Six additional courses of tegafur-uracil were given postoperatively to all 38 patients but 1 who refused.. As a result of preoperative chemoradiation treatment, 4 (10.5 percent) complete responses, 20 (52.6 percent) partial responses, and 14 (36.8 percent) patients with disease stabilization were observed. No patients had preoperative disease progression. Histologically proven downstaging was observed in 23 (60 percent) patients. On initial evaluation, only 39 percent of patients were considered as being good candidates for sphincter-preserving surgery; however, on preoperative chemoradiation completion this figure increased up to 60 percent. For the 23 patients eventually undergoing sphincter-preserving surgery, postoperative sphincter function assessment showed excellent function in 15 (65 percent) patients, good in 5 (22 percent), fair in 2 (9 percent), and poor in 1(4 percent). With a median follow-up of 37 (range, 10-62) months, local failure was found in 3 (8 percent) patients and distant failure in 2 (5 percent). Three-year actuarial disease-free survival and 3-year overall survival rates were 83 and 90 percent, respectively. Local control rate was 92 percent. Toxicity and postoperative complication rates were reasonable.. Our neoadjuvant radiation therapy protocol is efficient for the preoperative treatment of resectable rectal adenocarcinoma when combined with chemotherapy (oral tegafur-uracil modulated with leucovorin). this protocol needs to be tested in a phase-III clinical trial with a larger sample size.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Female; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Postoperative Complications; Radiotherapy Dosage; Radiotherapy, Adjuvant; Rectal Neoplasms; Tegafur; Treatment Outcome; Uracil

Continuous 5-fluorouracil (5-FU) infusion during radiation therapy is superior to the application of bolus 5-FU schedules. As an oral therapy, that provides prolonged fluoropyrimidine exposure, uracil and Tegafur (UFT) plus leucovorin (LV) has shown favorable activity with only moderate toxicity in colorectal cancer. The present study was designed to evaluate the safety of UFT+LV combined with pelvic radiation to determine the maximum-tolerated dose (MTD) in recurrent rectal cancer. Patients with recurrent rectal cancer received escalating doses of UFT (starting at 250 mg/m /day with 50 mg/m /day increments between consecutive cohorts) and fixed doses of LV (90 mg). The UFT+LV combination was given 5 days per week simultaneously to a 5-week course of irradiation up to a total dose of 50.4 Gy, 1.8 Gy daily fractions followed by a boost of 5.4 or 9.0 Gy to the gross tumor volume. Nineteen patients were treated and 14 received the full chemotherapy with delivery of all planned radiotherapy. The MTD of UFT was 400 mg/m /day due to the occurrence of dose-limiting diarrhea and emesis. Toxicities were mild and manageable on the lower dose levels. Treatment was feasible mainly on an outpatient base. We conclude that combined chemoradiation with oral UFT+LV is feasible and well tolerated for recurrent rectal cancer patients undergoing pelvic radiation. The safety profile appears comparable to that of i.v. dosing without requiring any i.v. port systems. The recommended doses for further phase II chemoradiation trials are 350 mg/m /day UFT+90 mg LV.

Topics: Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Drug Administration Schedule; Female; Humans; Leucovorin; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Recurrence, Local; Pelvis; Radiotherapy Dosage; Rectal Neoplasms; Tegafur; Treatment Outcome; Uracil

The gastrointestinal Intergroup studied postoperative adjuvant chemotherapy and radiation therapy in patients with T3/4 and N+ rectal cancer after potentially curative surgery to try to improve chemotherapy and to determine the risk of systemic and local failure.. All patients had a potentially curative surgical resection and were treated with two cycles of chemotherapy followed by chemoradiation therapy and two additional cycles of chemotherapy. Chemotherapy regimens were bolus fluorouracil (5-FU), 5-FU and leucovorin, 5-FU and levamisole, and 5-FU, leucovorin, and levamisole. Pelvic irradiation was given to a dose of 45 Gy to the whole pelvis and a boost to 50.4 to 54 Gy.. One thousand six hundred ninety-five patients were entered and fully assessable, with a median follow-up of 7.4 years. There was no difference in overall survival (OS) or disease-free survival (DFS) by drug regimen. DFS and OS decreased between years 5 and 7 (from 54% to 50% and 64% to 56%, respectively), although recurrence-free rates had only a small decrease. The local recurrence rate was 14% (9% in low-risk [T1 to N2+] and 18% in high-risk patients [T3N+, T4N]). Overall, 7-year survival rates were 70% and 45% for the low-risk and high-risk groups, respectively. Males had a poorer overall survival rate than females.. There is no advantage to leucovorin- or levamisole-containing regimens over bolus 5-FU alone in the adjuvant treatment of rectal cancer when combined with irradiation. Local and distant recurrence rates are still high, especially in T3N+ and T4 patients, even with full adjuvant chemoradiation therapy.

Topics: Adenocarcinoma; Adjuvants, Immunologic; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Drug Administration Schedule; Female; Fluorouracil; Follow-Up Studies; Humans; Injections, Intravenous; Leucovorin; Levamisole; Male; Middle Aged; Neoplasm Staging; Radiotherapy Dosage; Radiotherapy, Adjuvant; Rectal Neoplasms; Sex Factors; Survival Analysis; Treatment Outcome

We conducted a prospective randomized trial to define the optimal sequence of chemotherapy and radiotherapy of postoperative adjuvant treatment in stage II and III rectal cancer.. Three hundred eight patients were enrolled onto the study. We randomly assigned 155 to arm I (early radiotherapy group) and 153 to arm II (late radiotherapy group). Treatment included eight cycles of chemotherapy at 4-week intervals and pelvic radiotherapy of 45 Gy in 25 fractions. Radiotherapy started on day 1 of the first chemotherapy cycle in arm I and on day 1 of the third chemotherapy cycle in arm II. The chemotherapy regimen consisted of fluorouracil 375 mg/m(2)/d and leucovorin 20 mg/m(2)/d. Chemotherapy was administered for 3 days per cycle in two cycles during the period of radiotherapy and for 5 days per cycle in the remaining six cycles.. Twenty patients in arm I and 14 in arm II were not eligible. We included 274 patients in the analysis. With a median follow-up of 37 months for surviving patients, disease-free survival was significantly prolonged in arm I compared with arm II (81% v. 70% at 4 years; P =.043). Twenty-three recurrences occurred in arm I and 38 in arm II (P =.047). Overall survival was not significantly different between arms I and II (84% v. 82% at 4 years; P =.387).. Early radiotherapy with concurrent chemotherapy after resection of stage II and III rectal cancer demonstrated a statistically significant advantage for disease-free survival compared with late radiotherapy with chemotherapy.

Topics: Analysis of Variance; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Prospective Studies; Radiotherapy Dosage; Radiotherapy, Adjuvant; Rectal Neoplasms; Survival Analysis; Time Factors; Treatment Outcome

There is no consensus about the role of preoperative radiotherapy (RT) and chemotherapy (CT) in patients with resectable cancer of the distal rectum. This study analyzed the local clinical and pathologic response in patients receiving preoperative RT/CT for rectal cancer.. Thirty-two consecutive patients with a palpable adenocarcinoma of the rectum received preoperative RT (45 Gy in 25 fractions over 5 weeks) plus continuous chemotherapy with doxifluridine and leucovorin or 5-fluorouracil by continuous intravenous infusion during RT. Surgery was performed 8 weeks later. The Wilcoxon and chi(2) tests were used for data analysis.. Twelve patients had mild gastrointestinal toxicity, only one of whom required interruption of therapy. The tumor shrank to 57.8% of its original size, and at the echoendoscopy (u) there was a 58.7% decrease of the maximum diameter (P <.001). Downstaging from uT3 and uT2 to

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Floxuridine; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Rectal Neoplasms; Treatment Outcome

The object of this phase II study was to assess the impact of preoperative external radiation therapy combined with UFT and leucovorin on tumor response, sphincter preservation and tumor control in patients with rectal carcinoma.. Forty-one patients with resectable extraperitoneal rectal adenocarcinoma received radiation therapy and two courses of chemotherapy. Chemotherapy consisted of a 2-h infusion of 6S-steroisomer of leucovorin (6SLV) 250 mg/m2 on day 1, oral 6SLV 7.5 mg every 12 h on days 2-14, and UFT either 350 or 300 mg/m2 on days 1 to 14 every 28 days. Six additional courses of chemotherapy were given after surgery.. Seven of 16 patients (43%) who received 350 mg/m2/day of UFT had grade 3-4 diarrhea and two other patients (12%) had grade 3-4 dermatitis. The next 25 patients received 300 mg/m2/day of UFT and only 14% of them had grade 3-4 diarrhea. Surgery consisted of low-anterior resection in 26 patients (63%) and abdominal-perineal amputation in 15 (37%). There were six histological complete responses (15%). Downstaging occurred in 25 patients (63%). The overall survival at 3 years was 90% and the pelvic disease-free survival 92%.. Preoperative therapy with radiotherapy and UFT-6SLV downstaged 63% of tumors and allowed a sphincter-preserving procedure in some patients. Toxicity was moderate. This scheme is convenient because of the oral administration of chemotherapy.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluorouracil; Follow-Up Studies; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Radiation Dosage; Radiotherapy, Adjuvant; Rectal Neoplasms; Survival Analysis; Treatment Outcome

The main treatment for rectal carcinoma is surgery. Preoperative chemoradiation (CRT) is advocated to reduce local recurrence and improve resection of mid and low tethered rectal tumors.. Fifty-two patients with mid or low rectal tumors underwent CRT (external beam radiation plus 5-fluorouracil plus folinic acid). Patients who had low rectal tumors with complete response (CR) were not submitted to surgical treatment. All other patients were submitted to surgery, independently of the response. Mean follow-up was 32.1 months.. Five-year overall survival was 60.5%. Clinical evaluation after CRT showed CR in 10 cases (19.2%), all low tumors; incomplete response (>50%) in 21 (40.4%); and no response (<50%) in 19 (36.6%). Among the 10 cases with CR, 8 presented with local recurrence within 3.7 to 8.8 months. Two patients were not submitted to surgery and are still alive without cancer after 37 and 58 months. Thirty-nine patients had radical surgery. Seven had local recurrences after CRT plus surgery (17.9%). Overall survival was negatively affected by lymph node metastases (P =.017) and perineural invasion (P =.026).. Exclusive CRT approach is not safe to treat patients with low infiltrative rectal carcinoma.

Topics: Adenocarcinoma; Adult; Aged; Antimetabolites, Antineoplastic; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Radiotherapy Dosage; Rectal Neoplasms; Survival Rate

To determine the acute toxicity, outcome, and sphincter preservation rates in patients with clinically resectable uT3 adenocarcinoma of the rectum treated with preoperative combined modality therapy.. A total of 72 patients were treated from 12/90-7/98 with preoperative 50.4 Gy plus 2 cycles of concurrent 5-fluorouracil (5-FU) and leucovorin (LV) bolus daily x 5 followed by sharp or total mesorectal excision and 4 cycles of postoperative 5-FU and LV.. Individual Grade 3+ toxicities during preoperative therapy included diarrhea, 11%; bowel movements, 9%; leukopenia, 18%; tenesmus, 1%; and thrombocytopenia, 1%. Total Grade 3+ toxicity was 28%. The pathologic complete response (CR) rate was 13%, and an additional 9% had a clinical CR for a total CR rate of 22%. Of the 35 patients who were judged clinically by their operating surgeon to require an abdominoperineal resection (APR) and were therefore treated with the goal of sphincter preservation, 89% were able to undergo sphincter-preserving surgery. Of the 21 patients eligible for analysis, 81% had good to excellent sphincter function. The 3-year actuarial patterns of failure were 2% local, 8% abdominal, and 13% distant. The 3-year actuarial survival was 95%.. Our data confirm our preliminary reports of encouraging rates of acute toxicity, local control, survival, sphincter preservation and function with preoperative combined modality therapy. It is an alternative approach for the treatment of uT3 clinically resectable rectal cancer.

Topics: Adenocarcinoma; Anal Canal; Antimetabolites, Antineoplastic; Combined Modality Therapy; Disease-Free Survival; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Neoplasm Staging; Preoperative Care; Radiotherapy Dosage; Rectal Neoplasms; Treatment Failure

Preoperative radiation treatment with concomitant intravenous infusion of 5-fluorouracil (5-FU) is known to be effective in shrinking and downstaging of tumors. However, chemotherapy has often been limited by its toxicity and poor patient compliance. Oral 5-FU is known to have several advantages over conventional intravenous 5-FU infusion such as lower toxicity and higher quality of life without compromising the efficacy of the treatment. The aim of this study was to compare intravenous 5-FU with oral doxifluridine with respect to tumor response, toxicity and quality of life.. Twenty-eight patients with rectal cancer, staged as over T3N1 or T4 by transrectal ultrasonography between July 1997 and December 1998, were included in this study. Intravenous 5-FU (450 mg/m2) and leucovorin (20 mg/m2) were given for five consecutive days during the first and fifth weeks of radiation therapy (50.4 Gy) (n = 14). Oral doxifluridine (700 mg/m2/day) and leucovorin (20 mg/m2) were given daily during radiation treatment (n = 14). Quality of life was scored according to 22 activity items (good, >77; fair, >58; poor, <57). Surgical resection was performed 4 weeks after completion of concurrent chemoradiation treatment. Tumor response was classified into CR (complete remission), PR (partial response; 50% diminution of tumor volume or downstaging ) and NR (no response).. Tumor response was CR 3/14 (21.4%), PR 7/14 (50%) and NR 4/14 (28.6%) in the IV arm versus CR 2/14 (14.2%), PR 6/14 (42.9%) and NR 6/14 (42.9%) in the Oral arm (p = 0.16, 0.23, 0.24), respectively. The quality of life was poor (36.4% versus 33.3%), fair and good (63.6% versus 66.7%) between the IV arm and Oral arm, respectively. Gastrointestinal toxicity was 2/14 (14.3%) in the IV arm versus 5/14 (35.7%) in the Oral arm, respectively. Stomatitis was only observed in the IV arm (1/14, 7.1%). Hematological toxicity was 3/14 (21.4%) in the IV arm versus 4/14 (28.5%) in the Oral arm, respectively. Systemic recurrence during the follow-up periods were 1/14 (7.1%) in the IV arm and 2/14 (14.3%) in the Oral arm, respectively (p = 0.307). One local recurrence was observed in the Oral arm.. Even though the results were not entirely reliable owing to the small number of patients enrolled, oral doxifluridine-based chemotherapy as preoperative chemoradiation for advanced rectal cancer did not show any significant advantages over intravenous infusion.

Topics: Administration, Oral; Antimetabolites, Antineoplastic; Combined Modality Therapy; Female; Floxuridine; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Prospective Studies; Quality of Life; Rectal Neoplasms

The aim of this randomized open-label study was to compare a bimonthly with a monthly regimen of 5-fluorouracil (5-FU) and leucovorin for the adjuvant treatment of colon and high-rectum adenocarcinoma. The bimonthly regimen was administered for 2 consecutive days every 14 days as d,L-leucovorin 200 mg/m2 or L-leucovorin 100 mg/m2 as a 2-hour infusion followed by 5-FU bolus of 400 mg/m2 and a 600 mg/m2 5-FU 22-hour continuous infusion (LVSFU2). In the monthly regimen, d,L-leucovorin 200 mg/m2 or L-leucovorin 100 mg/m2 15-minute infusion followed by a 400 mg/m2 15 minute 5-FU bolus was administered for 5 consecutive days every 28 days (FUFOL). Nine hundred five patients with recently resected stage B2 or C colon or high-rectum adenocarcinoma (inferior pole of the tumor subperitoneal) were recruited into the study. Patients were randomized in a 2 x 2 factorial design to receive either LV5FU2 or FUFOL for 24 or 36 weeks. Characteristics of the patients in the two different treatment groups were similar at baseline. Compliance was good. Mean 5-FU dose intensities were 930 mg/ m2/wk and 463 mg/m2/wk for LVSFU2 and FUFOL, respectively. The incidence of maximal grade III-IV toxicities for LVSFU2 and FUFOL was neutropenia 6% and 16% (P < .001), diarrhea 4% and 10% (P < .001), and mucositis 2% and 7% (P < .001), respectively. Maximum grade III-IV toxicities in the LV5FU2 treatment group were significantly lower than in the FUFOL group (10% v 26%; P < .001). Although patients in the LV5FU2 group received twice the dose of 5-FU compared with those in the FUFOL group, LV5FU2 was shown to be less toxic. Efficacy data will be available in 2001.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Colonic Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Rectal Neoplasms

The aim of this study was to determine if the response to preoperative radiation and chemotherapy with continuous infusion 5-fluorouracil (5-FU) was predictive for survival among patients with locally advanced rectal cancer. Preoperative chemoradiation (CTX/XRT) that delivered 45 Gy in 25 fractions over 5 weeks with continuous infusion 5-FU (300 mg/m2/day) was given to 117 patients. The pretreatment stage distribution, as determined by endorectal ultrasound (u), included uT2N0 in 2%, uT3N0 in 47%, uT3N1 in 49%, and uT4N0 in 2% of cases; endorectal ultrasound was not performed in 13% of cases (15 patients). Approximately 6 weeks after completion of CTX/XRT, surgery was performed. Adjuvant chemotherapy, consisting of 400 to 425 mg/m2 of 5-FU plus 20 mg/m2 leucovorin for 5 days, was administered every 28 days for 4 to 6 cycles after surgical resection. Among the 74 patients treated with adjuvant chemotherapy, the preoperative stage of disease was 31 with T3N0 and 43 T3N1. Median follow-up was 46 months (range 2 to 89 months). The pathologic tumor stages were Tis-2N0 in 26%, T2N1 in 5%, T3N0 in 21%, T3N1 in 15%, T4N0 in 5%, and T4N1 in 1%; a complete response (CR) to preoperative CTX/XRT was pathologically confirmed in 32 (27%) of patients. Tumor down-staging occurred in 72 (62%) cases. A sphincter-saving procedure (SP) was possible in 59% of patients. The median DFS and overall survival rates for responders were 46 months and 47 months, respectively; for non-responders these outcome measures were 38 months and 41 months, respectively. Log-rank analysis showed that the distant metastatic-free survival rates improved with any response to CTX/XRT (p < 0.00001), CR to CTX/XRT (p < 0.009) and SP (p < 0.012). Likewise, these parameters also significantly influenced DFS rates (CTX/XRT p < 0.00001; CR p < 0.006; and SP p < 0.008). Control of pelvic disease was influenced by clinical size (p < 0.002) and SP (p < 0.016) on univariate analysis. On multivariate analysis only clinical size (p < 0.002) continued to be a significant factor for local control. Factors on multivariate analysis that resulted in significant improvements in cancer-specific survival included any response to preoperative CTX/XRT (p < 0.017) and administration of adjuvant chemotherapy (p < 0.034). Any response to preoperative CTX/XRT improved distant metastatic-free and disease-free survival rates. Multivariate analysis confirmed that a response to preoperative CTX/XRT predicted for improvements in

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Multivariate Analysis; Neoplasm Staging; Radiotherapy Dosage; Rectal Neoplasms; Survival Analysis

The aim of this study was to examine the efficacy and safety of both oxaliplatin as a single agent and oxaliplatin in combination with dailyx5 bolus 5-fluorouracil and folinic acid (5-FU/FA, Mayo clinic regimen) in the first-line treatment of metastatic colorectal cancer (CRC) patients. 73 advanced CRC patients were randomised to receive either oxaliplatin 85 mg/m(2) every 2 weeks (35 patients), or the same treatment combined with 5-FU 425 mg/m(2)/day and FA 20 mg/m(2)/dayx5 days every 4 weeks (38 patients). Treatment was continued until disease progression or unacceptable toxicity. All patients had documented inoperable disease and no previous chemotherapy for advanced disease. Based on the investigators' assessment of best response, objective response rate was 9% (95% confidence interval (CI) 2-24%) in the oxaliplatin arm, and 45% (95% CI 27-64%) in the oxaliplatin+5-FU/FA arm. Median progression-free survival (PFS) was 2 months (95% CI 1.7-2.4 months) in the oxaliplatin arm and 3.9 months (95% CI 2.9-5 months) in the oxaliplatin+5-FU/FA arm. Severe neutropenia was seen in 23% of patients in the oxaliplatin+5-FU/FA arm, and none in the oxaliplatin arm. There were two treatment-related deaths, both in the oxaliplatin+5-FU/FA arm. In the oxaliplatin+5-FU/FA arm, severe diarrhoea, vomiting and stomatitis were seen in 34, 14 and 14% of the patients, respectively. In conclusion, oxaliplatin at a dose of 85 mg/m(2) given every 2 weeks was well tolerated and has limited activity in metastatic CRC, while the combination of this treatment with the full-dose Mayo clinic regimen (5-FU bolus 425 mg/m(2)/day+FA 20 mg/m(2)/dayx5 days every 4 weeks), although active, was unfeasible due to a high level of myelosuppression and gastrointestinal toxicity. Alternative lower dosing or other regimens are to be explored to ascertain the value of bolus 5-FU/FA combined with oxaliplatin.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Disease-Free Survival; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms; Treatment Outcome

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Fluorouracil; Humans; Leucovorin; Neoplasm Recurrence, Local; Radiotherapy, Adjuvant; Rectal Neoplasms; Survival Analysis; Treatment Outcome; Vincristine

In a randomized study in primarily inextirpable rectal cancer, conventional radiotherapy to reduce the tumor mass was compared with combined chemotherapy and radiotherapy.. The combined treatment (CRT) was given every other week, four times, during a 7-week period. The drugs used were methotrexate, 5-fluorouracil in bolus injection followed by continuous infusion and leucovorin rescue. Radiotherapy (RT) was given simultaneously with five 2-Gy fractions in 3 days to a dose of 10 Gy to a total dose in the four courses of 40 Gy. This regimen was compared with radiotherapy in 2-Gy fractions to a total dose of 46 Gy in the radiotherapy group. Surgery was performed 3-4 weeks after finished treatment. Seventy patients were included between November 1988 and August 1996; 36 patients were allocated to RT and 34 to CRT.. Twenty-five (74%) of the patients in the CRT group underwent a locally radical resection with 20 (59%) patients without any known metastases. The corresponding figures in the RT group were 23 (64%) and 18 (50%), respectively. Among the patients who underwent any tumor resection, 5/29 (17%) in the CRT group and 12/27 (44%, p = 0.05) in the RT group have had a local recurrence. After a locally radical resection, the corresponding figures are 4% and 35% (p = 0.02), respectively. Local disease-free survival was significantly superior in the CRT group (66% at 5 years) compared with the RT group (38%, p = 0.03 log-rank test). Five-year survival was 29% (9 patients) in the CRT group and 18% (6 patients) in the RT group, a nonsignificant difference (p = 0.3). Five patients in the RT group did not complete planned treatment, mainly due to the appearance of metastatic disease. In this group toxicity was usually of Grade 0-1. In the experimental group, the toxicity usually was Grade 2 or higher, and 6 patients did not manage to fulfill the planned treatment due to toxicity.. In this study, with fewer included patients than intended, resectability rates were high in both groups. The addition of chemotherapy to radiotherapy significantly improved local control rates, but no statistically significant difference was found in survival between the groups. The acute toxicity after CRT was higher than after RT alone, but manageable.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Disease-Free Survival; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Radiotherapy; Rectal Neoplasms; Survival Rate

The use of oral chemotherapeutic agents in chemoradiotherapy provides several advantages. Doxifluridine, an oral 5-FU prodrug, has been shown to be effective in colorectal cancer. We attempted a Phase II trial of preoperative chemoradiotherapy with doxifluridine plus a low-dose oral leucovorin in unresectable primary rectal cancer patients. In this study, toxicity and efficacy were evaluated.. There were 23 patients with primary unresectable rectal cancer in this trial, 21 of whom were available for analysis. The patients were treated with oral doxifluridine (900 mg/day) plus oral leucovorin (30 mg/day) from days 1 to 35, and pelvic radiation of 45 Gy over 5 weeks. Surgical resection was performed 5-6 weeks after the treatment.. Acute toxicity involved thrombocytopenia, nausea/vomiting, diarrhea, and skin reaction. All were in Grade 1/2, except diarrhea, which was not only the most frequent (7 patients, 33.3%), but also the only toxicity of Grade 3 (2 patients). The clinical tumor response was shown in 5 patients (23.8%) as a complete response and 13 patients (61.9%) as a partial response. A complete resection with negative resection margin was done in 18 patients (85.7%), in 2 of whom a pathologic complete response was shown (9.5%). The overall downstaging rate in the T- and N-stage groupings was 71.4% (15 patients).. This study demonstrated the efficacy and low toxicity of chemoradiotherapy with doxifluridine. Currently, a Phase III randomized trial of chemoradiotherapy is ongoing at our institute to compare the therapeutic efficacy of oral 5-FU with respect to i.v. 5-FU in locally advanced and unresectable rectal cancer.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Diarrhea; Female; Floxuridine; Humans; Leucovorin; Male; Middle Aged; Preoperative Care; Radiotherapy; Rectal Neoplasms; Thrombocytopenia

Although preoperative chemoradiation for high-risk rectal cancer may improve survival and local recurrence rate, its adverse effects are not well defined. This prospective study evaluated the use of preoperative chemoradiation for T3 and T4 resectable rectal cancer, with special emphasis on treatment morbidity, pathologic remission rate, quality of life, and anorectal function.. Forty-two patients (30 men, 12 women) were enrolled in the study. Median distance of the distal tumor margin from the anal verge was 6.5 cm. Preoperative staging was based on digital rectal examination, endorectal ultrasound, and computed tomography. None of the patients had distant metastases. All patients had 45 Gy (1.8 Gy/day in 25 fractions) over five weeks, plus 5-fluorouracil (350 mg/m(2)/day) and leucovorin (20 mg/m(2)/day) bolus on days 1 to 5 and 29 to 33. Quality of life was assessed with the European Organization for Research and Treatment of Cancer 30-item quality-of-life questionnaire (QLQ-C30) and its colorectal cancer-specific module (QLQ-CR38) questionnaires. Objective anorectal function was assessed by anorectal manometry and pudendal nerve terminal motor latency. Surgery was performed 46 (range, 24-63) days after completion of adjuvant therapy.. Nineteen patients (45 percent) had Grade 3 or 4 chemoradiation-induced toxic reactions. Four patients developed intercurrent distant metastases or intraperitoneal carcinomatosis at completion of chemoradiation. Thirty-eight patients underwent surgical resection: abdominoperineal resection, anterior resection, and Hartmann's procedure were performed in 55 percent, 39 percent (11 of 15 patients had a diverting stoma), and 5 percent, respectively. Major surgical complications occurred in 7 patients (18 percent) and included anastomotic leak (n = 1), pelvic abscess (n = 1), small-bowel obstruction (n = 3), and wound breakdown (n = 2). Final pathology was Stage 0 (no residual disease), I, II, and III in 6 (16 percent), 7 (18 percent), 9 (24 percent), and 16 (42 percent) patients, respectively. There was a deterioration, after chemoradiation and surgery, in the quality of life on all subscales assessed, with physical, role, and social function being most severely affected. The symptoms most adversely affected were micturition, defecation, and gastrointestinal problems. Body image and sexual enjoyment deteriorated in both men and women. Chemoradiation alone led to prolonged pudendal nerve terminal motor latency in 57 percent of 7 patients assessed.. Preliminary results have identified defined costs with preoperative chemoradiation, which included treatment-induced toxicity, a high stoma rate, and adverse effects on quality of life and anorectal function.

Topics: Adenocarcinoma; Adult; Aged; Antimetabolites, Antineoplastic; Combined Modality Therapy; Dose Fractionation, Radiation; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Postoperative Complications; Quality of Life; Radiation Injuries; Radiotherapy, High-Energy; Rectal Neoplasms

Postoperative radio-chemotherapy has been established as standard treatment for stage II and III rectal cancer patients in the last decade. To improve the efficacy of this therapy, we decided to evaluate continuous 24-hour infusion of 5-fluorouracil (5-FU) with folinic acid (FA) in combination with local radiation versus standard bolus 5-FU/FA with local radiation in a randomized study. Here we report on the first 28 patients to receive the experimental treatment.. Patients with stage II and III rectal cancer received weekly 2-hour infusions of FA 500 mg/m2 followed by continuous 24-hour infusions of 5-FU 2,600 mg/m2 postoperatively via a Port-A-Cath system. The first cycle included 8 consecutive weekly administrations, the 1st-4th in full dose, the 5th-8th with 50% reduced dose while local irradiation (45 or 50.4 Gy) was performed. Thereafter, two further chemotherapy cycles (6 weekly administrations, 100% dose) followed.. 28 patients received continuous 5-FU/FA treatment, of whom only 21 were evaluable for tolerability. 19 patients (90.4%) completed the first cycle, only 14 patients entered the second treatment cycle. Especially during the combined radiochemotherapy, increased toxicity was observed with grade III/IV diarrhea (n = 2), nausea (n = 1), leukopenia (n = 1), and cardiac toxicity (n = 1).. The high rate of premature treatment dropout indicate that the chosen schedule of weekly high-dose 5-FU/FA continuous infusion and combined postoperative radiotherapy should not be recommended for further use in postoperative adjuvant treatment.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Administration Schedule; Feasibility Studies; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Patient Dropouts; Radiotherapy, Adjuvant; Rectal Neoplasms; Survival Rate

To assess antitumor activity and safety of two regimens in advanced colorectal cancer (CRC) patients with proven fluorouracil (5-FU) resistance in a randomized phase II study: 5-FU/folinic acid (FA) combined with alternating irinotecan (also called CPT-11) and oxaliplatin (FC/FO tritherapy), and an oxaliplatin/irinotecan (OC) combination.. Sixty-two patients were treated: arm FC/FO (32 patients) received, every 4 weeks, FA 200 mg/m(2) followed by a 400-mg/m(2) 5-FU bolus injection, then a 600-mg/m(2) continuous infusion of 5-FU on days 1 and 2 every 2 weeks administered alternately with irinotecan (180 mg/m(2) on day 1) and oxaliplatin (85 mg/m(2) on day 15). Arm OC (30 patients) received oxaliplatin 85 mg/m(2) and irinotecan 200 mg/m(2) every 3 weeks.. In an intent-to-treat analysis, two partial responses lasting 10.7 and 16 months were observed with the tritherapy regimen, and seven (median duration, 11 months; range, 10.6 to 11.4 months) were observed with the bitherapy regimen. Median progression-free and overall survival times were 8.2 and 9.8 months, respectively, in the FC/FO arm and 8.5 and 12.3 months, respectively, in the OC arm. Main grade 3/4 toxicities were, respectively, neutropenia, 53% and 47%; febrile neutropenia, 13% and 3%; diarrhea, 19% and 10%; vomiting, 6% and 13%; and neurosensory toxicity, 3% and 3%. No treatment-related deaths occurred.. The every-3-weeks OC combination is safe and active in advanced 5-FU-resistant CRC patients. The lower activity data seen with the tritherapy regimen may be related to the lower dose intensities of irinotecan and oxaliplatin in this schedule.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Colonic Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms; Survival Rate; Treatment Outcome

5-fluorouracil (5-FU) clearly behaves as two different drugs according to the schedules for its administration. A weekly, 8-h 5-FU continuous infusion (CI) regimen may produce a dual effect, because it elicits both a high plasma 5-FU level and also a durable exposure to 5-FU, which may have the advantage of inhibiting both DNA synthesis and RNA activities. The plasma 5-FU level, however, cannot be monitored in most hospitals, so we initiated a pragmatic clinical trial with this weekly 8-h 5-FU Cl regimen and adjusted the drug's dose according to the detected toxicity.. The initial dose of 5-FU was 1200 mg/m2 and this was escalated by 200 mg/m2 weekly, provided that no evidence of significant (grade 2 or greater) toxicity became apparent. Twenty-six patients entered the study from June 1998 to March 1999.. The median dose of 5-FU delivered was 1600 mg/m2. The major symptoms precluding dose escalation were nausea and vomiting. Seven patients demonstrated a partial response (26.9%), 11 patients revealed stable disease (42.3%) and eight exhibited progressive disease (30.8%).. This weekly 8-h CI 5-FU protocol with the adjustment of dose according to toxicity was not able to achieve the same 5-FU dose and response rate as in previous studies with pharmacokinetic monitoring of 5-FU levels. However, with the concurrent administration of intensive anti-emetic premedication, it is still possible to achieve adequate plasma 5-FU levels by adjusting the 5-FU dose according to elicited toxicity.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Nausea; Rectal Neoplasms; Vomiting, Anticipatory

To assess the efficacy and tolerability of three treatments for patients with documented adenocarcinoma of the colon and/or rectum who have undergone complete resection of primary tumor and have nonresectable liver metastases that do not exceed 75% of the liver volume.. A total of 168 patients at 25 treatment centers were enrolled onto this prospective, multicenter, randomized study. The three treatment arms were as follows: (1) fluorouracil (5-FU)/leucovorin (LV) administered via hepatic arterial infusion (HAI), (2) 5-FU/LV administered via intravenous (IV) infusion, and (3) fluorodeoxyuridine (FUDR) administered via HAI.. Median times to disease progression for the three treatment arms were as follows: 9.2 months for patients treated with HAI 5-FU/LV, 6.6 months for IV 5-FU/LV, and 5.9 months for HAI FUDR. Median survival times for patients treated with HAI 5-FU/LV, IV 5-FU/LV, and HAI FUDR were 18.7 months, 17.6 months, and 12.7 months, respectively. There was a nearly two-fold increase in time to progression in addition to a survival benefit among patients with an intrahepatic tumor burden of less than 25% who were treated with HAI 5-FU/LV. The most common adverse events were stomatitis, nausea and vomiting, skin irritation, diarrhea, and elevated serum levels of liver enzymes. Some patients exhibited severe reactions, including biliary sclerosis and chemical hepatitis.. Although the use of HAI 5-FU/LV as a means of treating liver metastases after resection of colorectal carcinoma warrants further investigation, it cannot be recommended as a routine therapeutic measure at this time.

Topics: Adenocarcinoma; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Catheters, Indwelling; Colonic Neoplasms; Disease Progression; Female; Floxuridine; Fluorouracil; Hepatic Artery; Humans; Infusions, Intra-Arterial; Infusions, Intravenous; Leucovorin; Liver Neoplasms; Male; Middle Aged; Rectal Neoplasms; Survival Analysis; Treatment Outcome

To assess toxicity and long-term results of preoperative chemoradiotherapy in rectal cancer.. Between 1989 and 1997, as a phase II study, 66 patients with T3 M0, rectal cancer received preoperatively a 45 Gy dose pelvic radiotherapy (XRT) combined with two 5-day chemotherapy courses (CT) of 5-Fluorouracil (5-FU) and Leucovorin (LV) delivered the first and fifth week of XRT. For each CT course, LV:20 mg/m2/d1-d5,. While the 5-FU dose was variable from 450 to 350 mg/m2/d first course and 370 to 350 mg/m2/d second course. Surgery was planned 3 weeks later.. XRT-CT was stopped in 1 patient due to progressive disease. CT was stopped in 1 patient due to toxicity. Grades 2 and 3 diarrhea were observed in 8 and 3 patients, respectively. One patient died from acute diarrhea due to deviation from recommendations; 60 patients went to surgery. Among the 58 patients operated on for cure, 5 had an R1-resection. After a 4.5-year median follow-up, the 5-year pelvic disease-free survival was 92% for the whole group and 96% in the R0-resection group.. Preoperative combined XRT-5-FU-LV is feasible if optimal XRT and patients are carefully managed. The recommended 5-FU daily dose is 350 mg/m2 for both CT courses. This approach is currently tested in a large EORTC phase III trial.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Combined Modality Therapy; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Radiotherapy Dosage; Rectal Neoplasms; Survival Analysis

The conviction that postoperative radiotherapy and chemotherapy represent an acceptable standard of care for patients with Dukes' B (stage II) and Dukes' C (stage III) carcinoma of the rectum evolved in the absence of data from clinical trials designed to determine whether the addition of radiotherapy results in improved disease-free survival and overall survival. This study was carried out to address this issue. An additional aim was to determine whether leucovorin (LV)-modulated 5-fluorouracil (5-FU) is superior to the combination of 5-FU, semustine, and vincristine (MOF) in men.. Eligible patients (n = 694) with Dukes' B or C carcinoma of the rectum were enrolled in National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol R-02 from September 1987 through December 1992 and were followed. They were randomly assigned to receive either postoperative adjuvant chemotherapy alone (n = 348) or chemotherapy with postoperative radiotherapy (n = 346). All female patients (n = 287) received 5-FU plus LV chemotherapy; male patients received either MOF (n = 207) or 5-FU plus LV (n = 200). Primary analyses were carried out by use of a stratified log-rank statistic; P values are two-sided.. The average time on study for surviving patients is 93 months as of September 30, 1998. Postoperative radiotherapy resulted in no beneficial effect on disease-free survival (P =.90) or overall survival (P =.89), regardless of which chemotherapy was utilized, although it reduced the cumulative incidence of locoregional relapse from 13% to 8% at 5-year follow-up (P =.02). Male patients who received 5-FU plus LV demonstrated a statistically significant benefit in disease-free survival at 5 years compared with those who received MOF (55% versus 47%; P =.009) but not in 5-year overall survival (65% versus 62%; P =.17).. The addition of postoperative radiation therapy to chemotherapy in Dukes' B and C rectal cancer did not alter the subsequent incidence of distant disease, although there was a reduction in locoregional relapse when compared with chemotherapy alone.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Disease-Free Survival; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Rectal Neoplasms; Semustine; Sex Factors; Survival Analysis; Time Factors; Vincristine

Standard adjuvant chemotherapy for colorectal cancer consists of fluorouracil with folinic acid or levamisole. The large QUASAR randomised trial aimed to investigate (in a two x two design) whether use of a higher dose of folinic acid or addition of levamisole to fluorouracil and folinic acid improved survival.. Patients with colorectal cancer, without evident residual disease, were randomly assigned fluorouracil (370 mg/m2) with high-dose (175 mg) or low-dose (25 mg) L-folinic acid and either active or placebo levamisole. The fluorouracil and folinic acid could be given either as six 5-day courses with 4 weeks between the start of the courses or as 30 once-weekly doses. Levamisole (50 mg) or placebo was given three times daily for 3 days repeated every 2 weeks for 12 courses. The primary endpoint was mortality from any cause. Analyses were by intention to treat.. Between 1994 and 1997, 4,927 patients were enrolled. 1,776 had recurrences and 1,576 died. Survival was similar with high-dose and low-dose folinic acid (70.1% vs 71.0% at 3 years; p=0-43), as were 3-year recurrence rates (36.0% vs 35.8%; p=0.94). Survival was worse with levamisole than with placebo (69.4% vs 71.5% at 3 years; p=0.06), and there were more recurrences with the active drug (37.0% vs 34.9% at 3 years; p=0.16).. The inclusion of levamisole in chemotherapy regimens for colorectal cancer does not delay recurrence or improve survival. Higher-dose folinic acid produced no extra benefit in these regimens over that from low-dose folinic acid. Trials of chemotherapy versus no chemotherapy will show whether these four treatments are equally effective or equally ineffective.

Topics: Adjuvants, Immunologic; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Colonic Neoplasms; Drug Therapy, Combination; Fluorouracil; Humans; Leucovorin; Levamisole; Neoplasm Recurrence, Local; Radiotherapy, Adjuvant; Rectal Neoplasms; Survival Analysis

To determine the maximum tolerated dose of oxaliplatin (L-OHP) given as a two-hour infusion followed by raltitrexed (Tomudex [TOM]) administered as a 15-min infusion on day 1, and bolus 5-fluorouracil (5-FU) modulated by a fixed dose of levo-folinic acid (LFA) 250 mg/m2 on day 2, recycling every two weeks, and to have preliminary evidence of activity of this combination in pretreated advanced colorectal cancer patients.. Fifty-two patients with advanced colorectal carcinoma previously treated with one (25 cases) or two or more lines of chemotherapy, including irinotecan (26 cases), and/or modulated 5-FU (40 cases) entered this study. Starting doses of L-OHP, TOM, and 5-FU were 85, 2.5 and 750 mg/m2, respectively.. Seven dose levels were tested. Neutropenia was the main dose limiting toxicity of the dose escalation (8 of 13 cases). The recommended doses were 130 mg/m2 of L-OHP, and 3.0 mg/m2 of TOM on day 1, followed by 250 mg/m2 of LFA, and 1050 mg/m2 of 5-FU on day 2, every two weeks. Severe diarrhoea and stomatitis were rarely reported. Most patients complained of mild peripheral sensitive aeurotoxicity, which was related to the cumulative dose of L-OHP. Twelve patients were considered as having a major responses (one complete), and an additional eight patients showed a minor response; the median time to treatment failure was twenty-four weeks.. With this regimen it is possible to give full doses of all three cytotoxic drugs every two weeks. Its activity and its manageable toxicity profile deserve further evaluation in pretreated advanced colorectal cancer patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Colonic Neoplasms; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Quinazolines; Rectal Neoplasms; Thiophenes; Treatment Outcome

Preoperative radiochemotherapy (RCT) is a widely used means of treatment for patients suffering from primary, locally advanced, or recurrent rectal cancer. We evaluated the efficacy of treatment due to additional application of regional hyperthermia (HRCT) to this conventional therapy regime in a Phase II study, employing the annular phased-array system BSD-2000 (SIGMA-60 applicator). The clinical results of the trial were encouraging. We investigated the relationship between a variety of thermal and clinical parameters in order to assess the adequacy of thermometry, the effectiveness of hyperthermia therapy, and its potential contribution to clinical endpoints.. A preoperative combination of radiotherapy (1.8 Gy for 5 days a week, total dose 45 Gy applied over 5 weeks) and chemotherapy (low-dose 5-fluorouracil [5-FU] plus leucovorin in the first and fourth week) was administered to 37 patients with primary rectal cancer (PRC) and 18 patients with recurrent rectal cancer (RRC). Regional hyperthermia (RHT) was applied once a week prior to the daily irradiation fraction of 1.8 Gy. Temperatures were registered along rectal catheters using Bowman thermistors. Measurement points related to the tumor were specified after estimating the section of the catheter in near contact with the tumor. Three patients with local recurrence after abdominoperineal resection, had their catheters positioned transgluteally under CT guidance, where the section of the catheter related to the tumor was estimated from the CT scans. Index temperatures (especially T(max), T(90)) averaged over time, cumulative minutes (cum min) (here for T(90) > reference temperature 40.5 degrees C), and equivalent minutes (equ min) (with respect to 43 degrees C) were derived from repetitive temperature-position scans (5- to 10-min intervals) utilizing software specially developed for this purpose on a PC platform. Using the statistical software package SPSS a careful analysis was performed, not only of the variance of thermal parameters with respect to clinical criteria such as toxicity, response, and survival but also its dependency on tumor characteristics.. The rate of resectability (89%) and response (59%) were high for the PRC group, and a clear positive correlation existed between index temperatures (T(90)) and thermal doses (cum min T(90) >/= 40.5 degrees C). Even though the overall 5-year survival was encouraging (60%) and significantly associated with response, there was no statistically significant relationship between temperature parameters and long-term survival for this limited number of patients. However, nonresectable tumors with higher thermal parameters (especially cum min T(90) >/= 40.5 degrees C) had a tendency for better overall survival. We found even higher temperatures in patients with recurrences (T(90) = 40.7 degrees C versus T(90) = 40.2 degrees C). However, these conditions for easier heating did not involve a favorable clinical outcome, since surgical resectability (22%) and response rate (28%) for the RRC group were low. We did not notice any other dependency of thermal parameters to a specific tumor or patient characteristics. Finally, neither acute toxicity (hot spots) induced by hyperthermia or RCT nor perioperative morbidity were correlated with temperature-derived parameters. Only a higher probability for the occurrence of hot spots was found during treatment with elevated power levels.. In this study with two subgroups, i.e., patients with PRC (n = 37) and RRC (n = 18), there exists a positive interrelationship between thermal parameters (such as T(90), cum min T(90) >/= 40,5 degrees C) and clinical parameters concerning effectiveness. Additional hyperthermia treatment does not seem to enhance toxicity or subacute morbidity. Procedures to measure temperatures and to derive thermal parameters, as well as the hyperthermia technique itself appear adequate enough to classify heat treatments in

Topics: Age Factors; Antimetabolites, Antineoplastic; Combined Modality Therapy; Female; Fluorouracil; Follow-Up Studies; Humans; Hyperthermia, Induced; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Preoperative Care; Radiotherapy Dosage; Rectal Neoplasms; Survival Rate

To study the impact of preoperative radiation dose escalation and postoperative adjuvant chemotherapy on the outcome of tethered and fixed rectal carcinoma.. We have treated 156 patients with 3 consecutive preoperative chemoradiation protocols with escalating treatment intensity. Schedule 1 consisted of 40 Gy radiation with concurrent 5-fluorouracil (5-FU) infusion and mitomycin C. Schedule 2 used a sandwich design with preoperative (40 Gy) and postoperative (18 Gy) radiation with concomitant 5-FU infusion, leucovorin, and mitomycin C. In schedule 3, the preoperative radiation dose was increased to 50 Gy and adjuvant 5-FU/leucovorin chemotherapy was added following surgery. There were 54, 27, and 75 patients treated in schedules 1, 2, and 3, respectively.. The resectability was 91% for schedule 1 and 100% for both schedules 2 and 3. A dose-response relationship was observed between the radiation dose and the tumor downstaging and local control. The pathological complete response (T0N0M0) rates for schedules 1, 2, and 3 were 4%, 15%, and 25%, respectively. The respective rates of tumor downstaging were 41%, 33%, and 68%, respectively. The 5-year local relapse-free rates were 67% for schedule 1 (40 Gy), 96% for schedule 2 (58 Gy), and 92% for schedule 3 (50 Gy) (p = 0.0011). The addition of postoperative chemotherapy appeared to improve both the survival and the relapse-free survival. The 5-year survival was increased from 52% to 84% (p = 0.0004) and the 5-year progression-free survival was improved from 48% to 74% (p = 0.0008).. Preoperative 5-FU infusion, leucovorin, mitomycin C, and 50-Gy pelvic radiation, followed by postoperative bolus 5-FU/leucovorin chemotherapy, appeared to be an effective treatment for tethered/fixed rectal cancers. However, its therapeutic efficacy could only be validated in randomized studies.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Dose-Response Relationship, Radiation; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Mitomycin; Neoplasm Staging; Preoperative Care; Radiotherapy Dosage; Rectal Neoplasms

Preoperative combined-modality therapy for rectal cancer may allow for sphincter preservation, while decreasing recurrence rates and improving the overall prognosis. Oral chemotherapy with uracil and tegafur (UFT) plus leucovorin (LV) may reduce costs and complications associated with protracted infusions of fluorouracil. Our goal was to evaluate the safety of UFT plus LV combined with preoperative radiation and determine the maximum-tolerated dose (MTD) and dose-limiting toxicity (DLT) of UFT plus LV in this setting.. Patients with tumor-node-metastasis stage II or III rectal cancer received escalating doses of UFT (starting at 250mg/m(2)/d, with 50-mg/m(2)/d increments between consecutive cohorts) and fixed doses of LV (90 mg/d). The UFT and LV combination was given 5 days per week concurrently with a 5-week course of preoperative radiation totaling 45 Gy (1.8 Gy/fraction). Surgery was performed 4 to 6 weeks after radiation and was followed by four 35-day cycles of fixed doses of UFT and LV (28 days of therapy each cycle).. Fifteen patients were treated, and 13 received the full preoperative chemotherapy. All planned radiation was delivered successfully. The MTD of UFT with radiation was 350 mg/m(2)/d with 90 mg/d of LV. Diarrhea was the DLT. Sphincter-preserving surgery was performed in 12 of 14 patients. One patient had progressive disease before surgery. Pathologic evaluation of 14 resected specimens showed a complete response in three cases.. Preoperative chemoradiation with oral UFT plus LV is feasible and well tolerated and should be further investigated.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Drug Administration Schedule; Female; Humans; Leucovorin; Male; Middle Aged; Postoperative Care; Preoperative Care; Rectal Neoplasms; Surgical Procedures, Operative; Tegafur; Uracil

The use of combined modality regimens has been well established in the treatment of stages II and III rectal cancer. The most common chemotherapy regimens used include continuous-infusion 5-FU delivered with the help of a central venous catheter and the use of portable pumps. These regimens are expensive and can potentially develop line problems. The availability of the oral agent UFT in combination with oral leucovorin prompted the development of an all-oral chemotherapy regimen that could be combined with radiotherapy. At The University of Texas M. D. Anderson Cancer Center, we routinely use combined chemotherapy and radiotherapy preoperatively for the treatment of rectal cancers, and decided to conduct a phase I trial in which UFT and leucovorin was used instead of the conventional 5-FU. The preliminary results are encouraging and seem to demonstrate the feasibility of this approach.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Leucovorin; Male; Middle Aged; Rectal Neoplasms; Tegafur; Treatment Outcome; Uracil

Postoperative combined-modality therapy with fluorouracil (5-FU) and radiation therapy is accepted practice for high-risk rectal cancer. Postoperative pelvic radiotherapy alone may improve pelvic control, but is not associated with an improvement in survival. Protracted infusional 5-FU has been associated with decreased tumor recurrence and improved survival when combined with postoperative adjuvant pelvic radiotherapy. The use of new drugs and alternative ways of administering 5-FU is desirable. UFT plus leucovorin is an oral 5-FU prodrug with efficacy equal to 5-FU plus leucovorin in metastatic colorectal cancer. A combination of postoperative adjuvant UFT plus leucovorin concurrent with radiation therapy should be feasible, and the design of an ongoing phase I trial is presented.

Topics: Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Leucovorin; Radiotherapy, Adjuvant; Rectal Neoplasms; Tegafur; Uracil

Environmental stress factors, such as heat, may induce multidrug resistance gene (mdr1) expression, which could result in the disadvantageous multidrug resistance (MDR) phenotype. To evaluate this possibility in a clinical situation, we investigated mdr1 gene expression in patients with locally advanced rectal cancer who underwent preoperative radio-chemo-thermo-therapy (RCTT). Patients were classified into groups according to the treatment schedule of RCTT vs. radio-chemo-therapy (RCT) without hyperthermia (control group). Expression of the mdr1 gene was analyzed in tumors and normal rectal tissues prior to and post-treatment (RCTT or RCT, respectively) by means of semi-quantitative and quantitative reverse transcription-polymerase chain reaction (RT-PCR). The data were correlated with therapeutic response and survival parameters. Based on our evaluation criteria, in 2 of 19 tumors of the RCTT group, mdr1 gene expression was increased more than 2-fold; in 3 of 19 tumors of this group, however, mdr1 expression was decreased more than 2-fold. In the patient control group, levels of mdr1 gene expression were reduced in 2 of 8 tumors. Thus, hyperthermia combined with RCT (RCTT) in comparison with RCT alone does not lead to an increase in mdr1 gene expression in patients with locally advanced rectal cancer within the preoperative treatment schedule. The risk of inducing the classical multidrug resistance phenotype by hyperthermia was thus minimal in this clinical setting. Subsequent adjuvant chemotherapy should thus not be hindered.

Topics: Antimetabolites, Antineoplastic; ATP Binding Cassette Transporter, Subfamily B, Member 1; Combined Modality Therapy; Disease-Free Survival; Dose Fractionation, Radiation; Drug Resistance, Multiple; Fluorouracil; Follow-Up Studies; Gene Expression Regulation, Neoplastic; Humans; Hyperthermia, Induced; Leucovorin; Prognosis; Rectal Neoplasms; Reverse Transcriptase Polymerase Chain Reaction; Survival Analysis; Time Factors

The objectives of the current study were: 1) to verify whether the addition of modulating low doses of interferon-2b (IFN) to 5-fluorouracil (5-FU) and levofolinic acid (1-FA) could improve clinical results in patients with advanced colorectal carcinoma; and 2) to evaluate the role of tumor burden and liver involvement as prognostic factors.. A total of 204 untreated patients were randomized to receive 1-FA at 100 mg/m2 and 5-FU at 375 mg/m2 for 5 consecutive days with or without IFN every 3 weeks. IFN was given subcutaneously at 3 MU/day for 7 days starting 2 days before chemotherapy administration. Patients were stratified according to the presence or absence of hepatic disease (H+ or H-) and to total tumor burden defined as "low" or "high" using an area of 10 cm2 as the cutoff value. Thus, four patient categories were obtained: Group 1: H+ > or = 10 cm2; Group 2: H+ < 10 cm2; Group 3: H- > or = 10 cm2; and Group 4: H- < 10 cm2.. No differences were observed in the objective response rate (23% for the combination of 1-FA and 5-FU vs. 24% for the 1-FA, 5-FU, and IFN regimen), median duration of response (11 months vs. 10 months), time to progression (5 months in both arms), and median survival (11 months vs. 12 months). A statistically significant improvement in response rate was observed in patients with limited liver involvement versus those with massive involvement independent of the chemotherapy arm (44% vs. 22%; P = 0.02). Overall survival also was improved in patients with limited liver disease (P = 0.0001) and in those without liver involvement (P = 0.004). Multivariate analysis confirmed these data and identified response and female gender as positive prognostic factors. Toxic side effects (mainly diarrhea, mucositis, and fever) were statistically more frequent in the IFN arm.. The addition of low modulating doses of IFN to the regimen of 5-FU and I-FA failed to increase the response rate and survival of patients with advanced colorectal adenocarcinoma and significantly worsened toxicity. High tumor burden and the presence of liver involvement were confirmed prospectively as poor prognostic factors and should be taken in account in designing future Phase II or comparative trials.

Topics: Adenocarcinoma; Adult; Aged; Analysis of Variance; Antidotes; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Female; Fluorouracil; Humans; Interferon alpha-2; Interferon-alpha; Leucovorin; Liver Neoplasms; Male; Middle Aged; Neoplasm Staging; Prospective Studies; Recombinant Proteins; Rectal Neoplasms; Survival Analysis

Local excision of rectal carcinoma has primarily been limited to patients with small (< or =3 cm), early rectal carcinoma. We wanted to determine whether local excision (transanal or transacral), when combined with selective chemoradiation therapy, would be adequate treatment for patients with larger (>3 cm) and more advanced T3 and N1 tumors.. A prospective study of 20 patients with clinical T1-T3, N0-N1 rectal carcinoma was initiated in 1990. Local excision (transanal or transacral) was performed on all patients. Sixteen patients were treated with postoperative 5-fluorouracil (5-FU) and leucovorin (LV) combined with radiation therapy; six high-risk patients (T3 or N1) received an additional 6 months of 5-FU and LV. All patients were followed for a minimum of 4 years.. Tumor size ranged from 2 to 5.5 cm (mean, 3.6 cm). Histology revealed well or moderate differentiation (19/20), gross or microscopic ulceration (14/20), and vessel invasion (5/20). Mucosal margins were 3-12 mm (mean, 8.3 mm); radial margins were clear in all patients except one (microscopically positive). Five patients had T3 tumors; two had node positive tumors (N1). With a median follow-up of 56 months (48-71), there have been no local or regional failures and two patients have died from metastatic disease.. Local excision, when combined with selective chemoradiation therapy, can be safely applied to patients with large (>3 cm) and more advanced T3 and N1 rectal carcinomas.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Prospective Studies; Rectal Neoplasms; Rectum

Systemic palliative chemotherapy is usually regarded as ineffective in disseminated colorectal cancer, and the risk of toxic adverse effects is often considered a contraindication, as many patients are old and cannot be offered curative treatment. Randomized trials during the last decade have shown, however, that an effect on both survival and quality of life can be expected. Only casuistic reports of total remission have been published but a partial tumour response can be expected in 20-50% of patients. Toxicity is related to palliative chemotherapy and accelerated with old age (> 70 years). When disseminated colorectal cancer is diagnosed the possibility of palliative chemotherapy should be conferred with an oncologist.

Topics: Age Factors; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Fluorouracil; Humans; Leucovorin; Meta-Analysis as Topic; Palliative Care; Quality of Life; Randomized Controlled Trials as Topic; Rectal Neoplasms

This study was designed to assess the toxicity of pelvic radiation therapy, 5-fluorouracil (5-FU) administered by protracted venous infusion, and leucovorin.. Pelvic radiation therapy consisted of 50.4-54 gray (Gy) administered in 28-30 fractions. Systemic treatment consisted of leucovorin (10 mg daily) administered orally and protracted venous infusion of 5-FU. The initial daily 5-FU dose was 150 mg/m(2). Dose escalations were planned in increments of 25 mg/m(2).. Forty eligible patients were registered, of whom 37 were evaluable for chemoradiotherapy-related toxicity. Grade 3 or 4 toxicity secondary to radiation therapy, protracted venous infusion of 5-FU, and leucovorin occurred in 2 of 17 patients at a daily 5-FU dose of 150 mg/m(2), in 5 of 10 patients at a daily 5-FU dose of 175 mg/m(2), and in 5 of 10 patients at a daily 5-FU dose of 200 mg/m(2). Diarrhea was dose-limiting in 7 of 8 patients with Grade 4 toxicity. Venous thrombosis, a treatment-related complication not directly related to chemotherapy or radiation therapy, occurred in 5 of the 40 patients entered into this study. Four thromboses occurred at the site of a central catheter. No thrombotic complications occurred in the last 7 patients, who were given warfarin orally (1 mg daily) during treatment.. Toxicity due to radiation therapy, protracted venous infusion of 5-FU, and leucovorin when 5-FU is given daily at a dose of 150 mg/m(2) is similar to that observed in current chemoradiotherapy regimens for patients with rectal carcinoma. This regimen will be considered as a possible investigational treatment arm of a future trial of adjuvant therapy for rectal carcinoma patients.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Chemotherapy, Adjuvant; Combined Modality Therapy; Dose-Response Relationship, Drug; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Pelvis; Rectal Neoplasms; Venous Thrombosis

Randomized studies have shown that postoperative chemotherapy with or without radiation therapy (RT) improved local control and survival of patients with stages II or III rectal cancer. However, the optimal sequence of treatments and the optimal chemotherapeutic regimen have not been defined. Modulation of fluorouracil (FU) by leucovorin (LV) has yielded a highly significant difference in response rate from that of FU monotherapy, as suggested by an overview of randomized trials in patients with advanced colorectal cancer. However, this difference in response rate did not translate into a survival benefit.. To evaluate the impact on the disease-free survival (DFS) and overall survival (OS) of patients with stages II or III rectal cancer of postoperative RT and concomitant bolus FU administration alone or with additional chemotherapy using FU and high-dose LV.. From October 1989 until February 1997, 220 patients were randomized postoperatively to receive either one cycle of chemotherapy with FU (600 mg/m2/week x 6 followed by a two-week rest) and leucovorin (LV, 500 mg/m2/week x 6 as a two-hour infusion) followed by pelvic RT with concomitant FU (400 mg/m2) as a rapid intravenous injection during the first three and last three days of RT, and three more cycles of the same chemotherapy with FU and LV (standard, group A, 111 patients) or pelvic RT with concomitant FU only (experimental, group B, 109 patients).. As of August 1998, after a median follow-up of 4.9 years, there was no significant difference in either three-year DFS (Group A, 70.3%; group B, 68.2%, P = 0.53) or OS (group A, 77%; group B, 73.3%. P = 0.75). Cox multivariate analysis revealed stage of disease, number of infiltrated nodes, tumor grade, presence of regional implants and perforation to be significant prognostic factors. The incidence of severe side effects was significantly higher in the patients in group A than in those in group B (32.4% vs. 4.6%, P < 0.0001).. The incorporation of additional chemotherapy with FU and LV into postoperative concomitant RT and bolus infusion of FU does not offer a > or = 10% three-year survival benefit over that of concomitant RT and bolus infusion of FU, and significantly increases toxicity in patients with stages II or III rectal cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Drug Administration Schedule; Female; Fluorouracil; Humans; Injections, Intravenous; Leucovorin; Male; Middle Aged; Rectal Neoplasms; Survival Analysis; Treatment Outcome

Uracil and tegafur (in a molar ratio of 4:1 [UFT]) plus calcium folinate comprise the components of the oral agent, Orzel, which appears to have activity comparable to intravenously administered 5-fluorouracil. This article describes the design of an open-label, disease-oriented, phase I trial of UFT plus calcium folinate in combination with simultaneous pelvic radiation for recurrent rectal cancer. This trial is designed to determine the maximum tolerated dose and dose-limiting toxicity of this regimen.

Topics: Antineoplastic Combined Chemotherapy Protocols; Follow-Up Studies; Humans; Leucovorin; Neoplasm Recurrence, Local; Radiotherapy, Adjuvant; Rectal Neoplasms; Safety; Tegafur; Treatment Outcome; Uracil

Protracted infusions of 5-fluorouracil (5-FU) combined with pelvic radiotherapy have been associated with improved survival and decreased local and distant metastases in the adjuvant therapy of rectal cancer. However, this method of 5-FU infusion requires the inconvenience and expense of central venous line placement and care, infusion pumps, and treatment of catheter-related complications. We previously demonstrated that a completely oral therapy with UFT (uracil plus tegafur in a 4:1 molar ratio) plus oral calcium folinate (Orzel) can achieve pharmacokinetic parameters similar to those associated with protracted 5-FU infusions. This trial examines the feasibility of using UFT plus oral calcium folinate both during preoperative pelvic radiation and postoperatively, and shows that patients can be treated safely and effectively with a completely oral chemotherapy program combining UFT plus oral calcium folinate with pelvic radiation therapy.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Drug Therapy, Combination; Follow-Up Studies; Humans; Leucovorin; Radiotherapy, Adjuvant; Rectal Neoplasms; Tegafur; Treatment Outcome; Uracil

To determine the activity and evaluate the toxicity of uracil and tegafur in a 4:1 molar concentration (UFT) plus low-dose leucovorin administered concomitantly with pelvic irradiation in patients with unresectable or recurrent rectal cancer.. Thirty-five patients (22 with primary unresectable tumors and 13 with locally recurrent tumors) were enrolled in the trial. Thirty-five patients were evaluable for toxicity and 32 of these were evaluable for clinical response. Patients received 300 mg/m2/day UFT and 30 mg/day leucovorin on days 8-35 concomitantly with pelvic radiotherapy, to a total dose of 45 Gy.. Eight of the 35 (23%) patients developed Grade 3 diarrhea and were treated with radiotherapy alone after this event. Of the 22 patients with unresectable primary tumors, 17 underwent surgery, and resection was feasible in 15 cases (88%). Of the 32 patients evaluable for clinical response, 4 (13%) had a complete clinical response (CR) and 22 (69%) a partial response (PR). A complete pathologic response was observed in 3 cases (18%) and, a PR in 11 cases (65%).. The response rates achieved with this schedule seem comparable to those obtained with 5-FU and radiotherapy. These results warrant further evaluation of this combination in patients with unresectable or locally advanced tumors.

Topics: Adult; Aged; Aged, 80 and over; Antidotes; Antimetabolites, Antineoplastic; Diarrhea; Disease-Free Survival; Female; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Rectal Neoplasms; Tegafur; Uracil

Twenty-seven patients with liver metastasis from colorectal cancer were treated with intermittent intra-arterial infusion chemotherapy for 5 years starting from 1993. Five to ten mg of CDDP, 250 mg of 5-FU and/or 3-6 mg of Leucovorin were administered weekly. In the case of nonresponders, the dose of 5-FU was allowed to increase toward 500 mg. The above schedule was repeated as long as possible. The average number of administrations in 12 out of 27 unresectable patients was 28.7. The response rate was 50% (CR; 4 cases, PR; 2), with 2 NC and 3 PD. Four patients given 500 mg of 5-FU showed some response. The 50% survival period was 466 days, and the 1- and 3-year survival rates were 66.7% and 18.3%, respectively. The average number of administrations in the group of patients who underwent prophylactic treatment and resection of the metastasis was 33.1. During an average observational period 681 days, 7 patients (46.7%) had a recurrence in the liver. The 5-year survival rate was 85.7%. The patients who were treated with 250 mg 5-FU experienced no severe side effects, but one who was given 500 mg 5-FU developed a duodenal ulcer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Colonic Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Hepatic Artery; Humans; Infusions, Intra-Arterial; Leucovorin; Liver Neoplasms; Male; Middle Aged; Rectal Neoplasms; Survival Rate

Postoperative combined modality therapy with radiotherapy and 5-fluorouracil (5FU) chemotherapy is an effective adjuvant approach that reduces locoregional and distant metastatic disease in patients with high-risk rectal carcinoma. However, this approach results in a treatment regimen of at least 6 months' duration. The present prospective study investigates the integration of radiotherapy and 5FU chemotherapy in a protocol designed to minimize toxicity and reduce the overall treatment time. A total of 40 patients with TNM stage II or III disease received postoperative radiotherapy at four fractions per week with weekly 5FU bolus injections delivered on the fifth non-radiotherapy day. Patients also received systemic chemotherapy with leucovorin both before and after pelvic irradiation, with the total treatment duration extending for only 18 weeks. Patients were able to complete radiotherapy in 90% of cases, while the delivery of full-dose chemotherapy was achievable in the vast majority. The incidence of haematologic and gastrointestinal toxicities requiring the cessation of treatment was acceptable. With a median follow-up of 20.9 months among surviving patients, the estimated progression-free and overall survival at 2 years were 71% and 79%, respectively.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Radiotherapy, Adjuvant; Radiotherapy, High-Energy; Rectal Neoplasms; Survival Rate

A relationship between fluorouracil (5-FU) dose and response has been previously shown in advanced colorectal cancer. In a previous study with 5-FU stepwise dose escalation in a weekly regimen, and pharmacokinetic monitoring, we defined a therapeutic range for 5-FU plasma levels: 2,000 to 3,000 microg/L (area under the concentration-time curve at 0 to 8 hours [AUC0-8], 16 to 24 mg x h/L). The current study investigated 5-FU therapeutic intensification with individual dose adjustment in a multicentric phase II prospective trial.. Weekly high-dose 5-FU was administered by 8-hour infusion with 400 mg/m2 leucovorin. The initial dose of 5-FU (1,300 mg/m2) was adapted weekly according to 5-FU plasma levels, to reach the therapeutic range previously determined.. A total of 152 patients entered the study from December 1991 to December 1994: 117 patients with measurable metastatic disease and 35 with assessable disease. Toxicity was mainly diarrhea (39%, with 5% grade 3) and hand-foot syndrome (30%, with 2% grade 3). Among 117 patients with measurable disease, 18 had a complete response (CR), 48 a partial response (PR), 35 a minor response (MR) and stable disease (SD), and 16 progressive disease (PD). Median overall survival time was 19 months. The 5-FU therapeutic plasma range was rapidly reached with a variable 5-FU dose in the patient population: mean, 1,803 +/- 386 mg/m2/wk (range, 950 to 3,396). Thirteen patients were immediately in the toxic zone, whereas 51 required a > or = 50% dose increase.. Individual 5-FU dose adjustment with pharmacokinetic monitoring provided a high survival rate and percentage of responses, with good tolerance.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Colonic Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Rectal Neoplasms; Survival Analysis

Patients with colorectal carcinoma progressing after a 5-fluorouracil (5-FU)-containing regimen were eligible. One treatment cycle consisted of repeated administrations of 5-FU combined to folinic acid for six times and to oxaliplatin for three times over 50 days. 5-FU was given at the dose of 2.6 g/m2 as a continuous infusion over 24 h on days 1, 8, 22, 29 and 43 preceded by i.v. folinic acid (FA) at a dose of 500 mg/m2 over 1 h. Oxaliplatin was given 1 h after 5-FU at the dose of 130 mg/m2 over a 2 h infusion on days 1, 22 and 43. A total of 37 patients were treated according to this schedule. The rates of objective responses after the first and second treatment cycles were 28 and 17%, respectively, with rates of tumor growth control, i.e. including the stabilizations, of 55 and 28%. The median duration of response was 10 months and the median duration of stabilizations was 6 months. The median survival time from initiation of oxaliplatin-containing therapy is 10 months (2-28+). The median survival time from the diagnosis of metastatic disease is 24 months (2-40+). The main toxicities were leucopenia, diarrhea, fatigue and paresthesias. The combination of 5-FU/FA/oxaliplatin was well tolerated and appears as a meaningful therapy after failure of a previous 5-FU-containing treatment.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Colorectal Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms; Survival Analysis; Time Factors

We have used a relatively new trial methodology, the group sequential design, to prospectively evaluate two dose levels of bolus/infusional 5-fluorouracil (5-FU) and folinic acid in 192 consecutive-patients with advanced colorectal carcinoma. On day 1, all patients received 200 mg m(-2) of folinic acid infusion over 2 h. Cohort A (n = 102 patients) received 500 mg m(-2) 5-FU by i.v. 15-min infusion followed by an infusion of 500 mg m(-2) 5-FU over 22 h. Treatment was repeated on day 2 and further cycles given 2-weekly. After sequential analysis excluded a response rate of over 40%, cohort B (n = 90 patients) received an increased dose of 600 mg m(-2) 5-FU bolus and infusion. Patients had received no prior 5-FU therapy and the two cohorts had similar demographic features. In 179 evaluable patients, the overall response rate was 18% (95% CI 12-24%) with CR of 6% and PR of 12%, with no difference between the two cohorts. Overall median survival was 34 weeks (95% CI 30-39) with no significant difference between cohorts (median survival 32 and 37 weeks in cohort A and B respectively; P = 0.27). On multivariate analysis, poor performance status, elevated initial WBC and alkaline phosphatase and low serum albumin were associated with reduced survival (P < 0.05), and initial raised WBC showed an association with reduced likelihood of response (P = 0.002). Overall toxicity was low with CTC grade 3 mucositis, diarrhoea, nausea or vomiting in < or = 6% of patients and no treatment-related deaths. Significant (grade 3 or above) leucopenia was more common in cohort B than in cohort A (9% and 1% respectively); there were more dose reductions, and the median administered dose intensity was lower in cohort B than in cohort A (89% and 97% respectively; P = 0.006). In this group of relatively unselected patients, we have confirmed a relatively low objective response rate and median survival of 7.8 months with this regimen. There was no significant difference in outcome between the two dose levels but the higher dose of 5-FU was associated with more dose reductions and greater toxicity.

Topics: Adult; Aged; Aged, 80 and over; Antidotes; Antimetabolites, Antineoplastic; Carcinoma; Cohort Studies; Colonic Neoplasms; Drug Therapy, Combination; Fluorouracil; Humans; Leucovorin; Middle Aged; Prospective Studies; Rectal Neoplasms; Survival Rate; Treatment Outcome

To determine the acute toxicity, post-operative complications, pathologic response and extent of downstaging to high dose pre-operative radiation using a hyperfractionated radiation boost and concurrent chemotherapy in a prospective Phase I trial.. To be eligible for this study, patients had to have adenocarcinoma of the rectum less than 12 cm from the anal verge with either Stage T4 or T3 but greater than 4 cm or greater than 40% of the bowel circumference. All patients received 45 Gy pelvic radiation (1.8 Gy per fraction). Subsequent radiation was given to the region of the gross tumor with a 2 cm margin. This "boost" treatment was given at 1.2 Gy twice daily to a total dose of 54.6 Gy for Level I, 57 Gy for Level II, and 61.8 Gy for Level III. 5-FU was given at 1g/m2 over 24 hours for a four day infusion during the first and sixth weeks of radiation, with the second course concurrent with the hyperfractionated radiation. Surgical resection was carried out 4-6 weeks following completion of chemoradiation (in curative cases) and additional adjuvant chemotherapy consisting of 5-FU and Leucovorin was given for an additional 4 monthly cycles Days 1 through 5 beginning four weeks post surgery.. Twenty-seven patients, age 40-82 (median 61), completed the initial course of chemoradiation and are included in the analysis of toxicity. The median follow-up is 27 months (range 8-68). Eleven patients were treated to a dose of 54.6 Gy, nine patients to 57 Gy, and seven patients to 61.8 Gy. Twenty-one patients had T3 tumors, and six patients T4 tumors. Grade III acute toxicity from chemoradiation included proctitis (5 patients), dermatitis (9), diarrhea (five), leukopenia (1), cardiac (1). Grade IV toxicities included one patient with diarrhea (on dose Level I) and one patient (on dose Level III) with cardiac toxicity (unrelated to radiation). Surgical resection consisted of abdominal perineal resection in 16 and low anterior resection in 7. Four patients did not undergo a curative resection; three initially presented with metastases and one developed metastasis during the pre-operative regimen. Post-operative complications included pelvic or perineal abscess in two (on dose Levels I & II), and delayed wound healing in two (one of whom, on dose Level III, developed perineal wound dehiscence requiring surgical reconstruction). Of the 23 patients who had a curative resection, four manifested pathologic complete responses (17.4%). Thirteen of 23 patients (57%) had evidence of pathologic downstaging and only 1/23 patients (on dose Level I) had a positive resection margin. Of these 23 patients (with a minimum follow-up of 8 months), the patient with positive margins was the only one who developed a local failure (Fisher's Exact p=.04). The 3-year actuarial OS, DFS and LC rates are 82%, 72% and 96%, respectively. Twelve of 13 patients (92% at 3 years) > or = 61 years vs. 5/10 patients (45% at 3 years) < 61 years remained disease-free (log-rank p=0.017).. This regimen of high dose pre-operative chemoradiation employing a hyperfractionated radiation boost is feasible and tolerable and results in significant downstaging in locally advanced rectal cancer. The vast majority of patients (96%) achieved negative margins, which appears to be a prerequisite for local control (p= 0.04). Older age (> or =61 years) was a significant predictor for improved DFS. This regimen (at dose Level III, 61.8 Gy) is currently being tested in a Phase II setting.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antidotes; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Disease-Free Survival; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Middle Aged; Postoperative Complications; Prospective Studies; Radiotherapy Dosage; Rectal Neoplasms; Treatment Failure

Data from 12 metastatic colorectal cancer patients who were submitted to a pilot study with a multistep subcutaneous (sc) low dose recombinant interleukin-2 (rIL-2), 5-fluorouracil (5-FU) and leucovorin (LV) administration were compared with those from 13 historical controls who were comparable for the major prognostic indices. All 12 patients in the pilot study were subjected initially to six to eight courses of 5-FU-LV by endovenous (ev) bolus consistent with the Machover schedule alternating with 6 weeks of rIL-2 cycles. At the progression of metastatic disease, the patients were given 500 mg/m2 per day of 5-FU by continuous infusion (ci) for 5 days every 4 weeks and in case of further progression, 2,600 mg/m2 of 5-FU by 24-h ci once a week for 6 weeks. The control patients were treated with 5-FU-LV by the Machover schedule until progression and then observed. As yet, two patients in the pilot study and three control patients are currently alive. In the pilot study, the patients' response rate (CR + PR) and overall response rate (CR + PR + SD) were much higher than in the controls (50 vs 23% and 92 vs 54%, respectively). Time duration of response and survival from primary surgery were more prolonged in the pilot study than in the historical control, although not significantly (10.5 vs 6 and 41.5 vs 29 months, respectively). Time from starting therapy to progression and survival from relapse were significantly in favour of the pilot study (11.5 vs 4 and 31 vs 13.5 months; P < 0.01 and P < 0.05 unpaired t-test, respectively). Low dose s.c. rIL-2 cycles were well tolerated and no interruption occurred. In the pilot study sporadic grade 3 toxicity (diarrhoea or leucopenia) was responsible for the reduction of 5-FU doses to 80% of the previous infusion, but no treatment was postponed. In conclusion, these preliminary data suggest the opportunity to initiate large prospective randomized trials using a multistep therapy with rIL-2, 5-FU ci at conventional and at high dose in metastatic colorectal cancer.

Topics: Aged; Colonic Neoplasms; Colorectal Neoplasms; Female; Fluorouracil; Follow-Up Studies; Humans; Interleukin-2; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Pilot Projects; Rectal Neoplasms; Survival Rate

Recent studies show that preoperative radio-chemotherapy can increase resectability and local control of locally advanced rectal carcinomas. Additional regional hyperthermia might increase remission rates and tumor response. We therefore tested regional hyperthermia together with radio-chemotherapy in a phase-II study on locally advanced rectal carcinomas.. Thirty-seven patients with primary advanced stage uT3/T4 rectal carcinomas were treated with preoperative radio-chemo-thermo-therapy. The initial tumor depth was determined using endosonography, CT, and MRI. Radiotherapy was carried out in prone position (on a belly board) using standard techniques, with 5 x 1.8 Gy per week up to 45 Gy at the reference point. 5-Fluorouracil (300 to 500 mg/m2) was administered with low doses of leucovorin (50 mg) on days 1 to 5 and 22 to 28. The patients were treated with regional hyperthermia each week prior to radiotherapy and simultaneously with chemotherapy, using the Sigma 60 ring from the BSD-2000 system. Temperature/position curves and temperature/time curves were recorded in endocavitary (endorectal) catheters in tumor contact and as well in bladder and vagina. Following endosonographic restaging, the operation was carried out 4 to 6 weeks after the end of preoperative therapy and adjuvant chemotherapy continued in four cycles. In cases where tumors were non-resectable, a boost up to 64 Gy was aimed.. Thirty-one of the 37 patients (84%) with primary carcinoma proved locally R0-resectable. In addition we had 1 R1-resection (3%) and 5 non-resectable tumors (13%). Among the resected tumors, 53% experienced a reduction of depth infiltration from the initial endosonographic stage during preoperative therapy. The actuarial survival rate after 4 years is 65% (free of progression 57%). The actuarial 4-year survival rate was particularly favorable for the group of responders. Overall, the preoperative multimodal therapy was well tolerated, and premature termination was only necessary in 1 case (3%). Grade III/IV toxicities in the intestine and skin were reduced as far as possible by field blockings and cooling of the perineal region. They occurred only in 5/37 patients (13%) at the intestine and in 6/37 patients (16%) at the skin. The thermal data were subjected to a statistical analysis. The quality of temperature distribution (T90, cum min T90 > or = 40.5 degrees C) depends on the power level and relative power density. The response (reduction of tumor size or depth infiltration) correlated significantly with quality parameters of the temperature distributions. This dependency is found as a trend for progression-free survival, too.. Preoperative radio-chemo-thermo-therapy proved to be practical and effective, with encouraging remission rates and excellent local control rates. For this reason, a phase-III study to test regional hyperthermia has been initiated. At the same time, certain technical improvements are still under development for regional hyperthermia.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Combined Modality Therapy; Female; Fluorouracil; Follow-Up Studies; Humans; Hyperthermia, Induced; Leucovorin; Male; Middle Aged; Preoperative Care; Radiotherapy Dosage; Rectal Neoplasms; Time Factors

In a prospective multi-institutional German adjuvant trial patients with curatively resected rectal cancer (Dukes B or C) were randomly assigned to receive postoperative radiotherapy (50.4 Gy) and either 12 or 6 cycles of 5-fluorouracil and medium-dose folinic acid. Our preliminary results of the interim analysis, based on 206 patients, indicate that this adjuvant therapy is well tolerated by the patients and a prolonged chemotherapy over 12 months has no advantage over 6 months of chemotherapy. The relatively high rate of tumor recurrence (30.7%) after a median follow-up of 29.3 months in this trial emphasizes the need for dose intensification planned for a further trial.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Prospective Studies; Radiotherapy, Adjuvant; Rectal Neoplasms; Treatment Outcome

Twenty-three patients with metastatic colorectal carcinoma were randomized as part of two multicenter Phase III trials to receive either 5-fluorouracil (5-FU)/interferon alpha-2A (INF-alpha) or 5-FU +/- leucovorin. The patients were evaluated regularly for response by CT of the abdomen when treatment began and then every six to eight weeks. incidentally, we found that four of 13 patients treated with 5-FU/INF-alpha and none of ten patients treated with 5-FU +/- leucovorin developed hepatic steatosis during treatment. The diagnoses were based on a decreased CT value of the liver parenchyma by the repeated CT, and histologically verified by liver biopsies. There was no relationship to cumulative 5-FU or INF-alpha dose. Based on posttreatment CT, the liver parenchyma changes were reversible after therapy was stopped. Recognition of this condition in patients receiving 5FU/INF-alpha is important to prevent a patient from being labeled as having progressive hepatic metastases.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Agents; Colonic Neoplasms; Fatty Liver; Female; Fluorouracil; Humans; Interferon-alpha; Leucovorin; Liver; Male; Middle Aged; Radiography; Rectal Neoplasms

A phase II study to evaluate the response rate and toxicities of a trimetrexate, fluorouracil (5FU), and leucovorin regimen in patients with advanced incurable colorectal cancer.. Thirty-six patients with unresectable or metastatic colorectal cancer who had not been treated for advanced disease received the following chemotherapy regimen weekly for six courses every 8 weeks: trimetrexate 110 mg/m2 intravenously (I.V.) on day 1, leucovorin 200 mg/m2 I.V. on day 2 (24 hours later), 5FU 500 mg/m2 on day 2 immediately following leucovorin, and oral leucovorin 15 mg every 6 hours for seven doses starting 6 hours after 5FU. Patients were treated until progression or unacceptable toxicity.. Thirty patients were assessable for response, and all 36 were assessable for toxicity. Two patients (7%) achieved a complete response (CR) and 13 (43%) a partial response (PR), for an overall response (OR) rate of 50% (95% confidence interval [CI], 32% to 68%). Analysis by intent to treat demonstrated a 42% OR rate (95% CI, 26% to 58%). At final analysis, 16 patients were alive. The median survival duration for the entire cohort was 53.4 weeks. Gastrointestinal toxicity was most common, with 21 patients (58%) having grade 3/4 diarrhea and 12 patients (34%) grade 3/4 nausea. Hematologic toxicity was generally low grade, although two patients died of sepsis.. The combination of trimetrexate with 5FU and leucovorin is active in metastatic colorectal cancer. Gastrointestinal toxicity with this regimen is most prominent, but is manageable.

Topics: Adult; Aged; Aged, 80 and over; Antidotes; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Rectal Neoplasms; Trimetrexate

We report the local control and survival of two Phase I dose escalation trials of combined preoperative 5-fluorouracil (5-FU), low-dose leucovorin (LV), and radiation therapy followed by postoperative LV/5-FU for the treatment of patients with locally advanced and unresectable rectal cancer.. A total of 36 patients (30 primary and 6 recurrent) received two monthly cycles of LV/5-FU (bolus daily x 5). Radiation therapy (50.40 Gy) began on day 1 in the 25 patients who received concurrent treatment and on day 8 in the 11 patients who received sequential treatment. Postoperatively, patients received a median of four monthly cycles of LV/5-FU.. The resectability rate with negative margins was 97%. The complete response rate was 11% pathologic and 14% clinical for a total of 25%. The 4-year actuarial disease-free survival was 67% and the overall survival was 76%. The crude local failure rate was 14% and the 4-year actuarial local failure rate was 30%. Crude local failure was lower in the four patients who had a pathologic complete response (0%) compared with those who either did not have a pathologic complete response (16%) or who had a clinical complete response (20%).. Our preliminary data with the low-dose LV regimen reveal encouraging downstaging, local control, and survival rates. Additional follow-up is needed to determine the 5-year results. The benefit of downstaging on local control is greatest in patients who achieve a pathologic complete response.

Topics: Adult; Aged; Antidotes; Antimetabolites, Antineoplastic; Combined Modality Therapy; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Rectal Neoplasms

National Surgical Adjuvant Breast and Bowel Project Protocol R-03 was designed to determine the worth of preoperative chemotherapy and radiation therapy in the management of operable rectal cancer.. Thus far, 116 patients of an eventual 900 with primary operable rectal cancer have been randomized to receive multimodality therapy to begin preoperatively (59 patients) or identical therapy beginning after curative surgery (57). All patients received seven cycles of 5-fluorouracil (FU)/leucovorin (LV) chemotherapy. Cycles 1 and 4 through 7 used a high-dose weekly FU regimen. In Cycles 2 and 3, FU and low-dose LV chemotherapy was given during the first and fifth week of radiation therapy (5,040 cGy). The preoperative arm (Group 1) received the first three cycles of chemotherapy and all radiation therapy before surgery. The postoperative arm (Group 2) received all radiation and chemotherapy after surgery. Primary study end points included disease-free survival and survival. Secondary end points included local recurrence, primary tumor response to combination therapy, tumor downstaging, and sphincter preservation.. Overall treatment-related toxicity was similar in both groups. Although seven preoperative patients had events after randomization that precluded surgery, eight events occurred during an equivalent follow-up period in the postoperative group. No patient was deemed inoperable because of progressive local disease. Sphincter-saving surgery was intended in 31 percent of Group 1 patients and 33 percent of Group 2 patients at the time of randomization. Such surgery was actually performed in 50 percent of the preoperatively treated patients and 33 percent of the postoperatively treated patients. The use of protective colostomy in patients undergoing sphincter-sparing surgery and the development of perioperative complications in all surgical patients were similar in both groups. There was evidence of tumor downstaging in evaluable patients undergoing preoperative therapy, with 8 percent of Group 1 patients having had a pathologic complete response.. These data do suggest that the preoperative chemotherapy and radiation therapy regimen used are, at least, as safe and tolerable as standard postoperative treatment. There is presently a trend to tumor downstaging and sphincter preservation in the preoperative arm. Whether this arm will have greater or lesser survival and long-term toxicity awaits the completion of this relevant study.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Postoperative Care; Postoperative Complications; Preoperative Care; Radiotherapy Dosage; Radiotherapy, Adjuvant; Rectal Neoplasms

The purpose of this phase II study was to evaluate the efficacy and toxicity of fluorouracil and high-dose leucovorin (5-FU/LV) with pelvic irradiation as adjuvant therapy for patients with macroscopical resected rectal or recto-sigmoid cancer. Following surgery for stages II-III primary (52) or recurrent rectal cancer (4), 56 patients received 8 cycles of 5-FU/LV and pelvic irradiation. 5-FU doses were 200 mgr/m2 for cycles 2-3 and 300 mgr/m2 for cycles 1 and 4-8. LV doses remained fixed at 200 mgr/m2. Pelvic radiation was started in the third week, between the first and second cycle. The total dose was 50.4 Gy. No severe complications had been recorded. The incidence of grade 3 diarrhea was 19%. Three patients presented leukopenia grade 3 (5%). In 44 patients (78%) the planned treatment could be administered. The median follow-up was 40 months (range 22-66). Seven patients had a local relapse (13%) and 6 developed distant metastasis (10%). The 3-year disease-free survival was 72% and the overall survival was 76%. These preliminary results show that combined post-operative 5-FU/LV and pelvic radiotherapy are well tolerated and present a reasonable local control and survival rates. This adjuvant treatment should be evaluated in randomized trials.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Radiotherapy Dosage; Radiotherapy, Adjuvant; Rectal Neoplasms; Sigmoid Neoplasms; Survival Analysis; Treatment Outcome

Oxaliplatin has shown in vivo cytotoxic activity against colorectal cell lines. Preliminary studies suggest potentiation of fluorouracil (5-FU). To assess this issue, we performed a phase II study in pretreated patients with advanced colorectal cancer (CRC) resistant to leucovorin and 5-FU. The regimen (FOLFOX2) consisted of oxaliplatin 100 mg/m2 as a 2-h infusion on day 1; leucovorin 500 mg/m2 as a 2-h infusion, followed by 5-FU 24-h infusion 1.5-2 g/m2 for two consecutive days every 2 weeks. The initial 5-FU dose was 1.5 g/m2 for two cycles and increased to 2 g/m2 in case of no toxicity > grade 2. 46 patients were treated, all with disease progression on leucovorin and 5-FU therapy for metastatic disease, or relapse less than 6 months after the end of adjuvant therapy. One complete response (CR) and 20 partial responses (PRs) were observed for an overall response rate of 46%. 22 patients had prior documented progression while receiving the same schedule of leucovorin and 5-FU as the one used in the FOLFOX2 regimen, and among them, 10 had PRs (45%). From the start of FOLFOX2, median progression-free survival was 7 months and median survival 17 months. WHO toxicity > or = grade 3 per patient was: peripheral neuropathy 9%, nausea 4%, diarrhoea 9%, mucositis 13%, neutropenia 39%, thrombocytopenia 11%, alopecia 9%, and allergy 2%. Overall, 21 patients (46%) experienced grade 3-4 toxicity. This combination of leucovorin, 5-FU and oxaliplatin achieves a high response rate in pretreated patients with CRC resistant to leucovorin and 5-FU. Limiting toxicities are neutropenia and peripheral neuropathy.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms; Survival Rate; Treatment Outcome

The combination of radiation therapy with fluorouracil (5-FU)-based chemotherapy is generally accepted as appropriate postoperative therapy for patients with adenocarcinomas of the rectum that extend through the bowel wall or with lymph nodes positive for tumor. We attempted to determine whether the efficacy of this postoperative therapy could be improved by the addition of leucovorin and/or levamisole.. A total of 1,696 patients were randomized and eligible for treatment with one of four treatment schemes. All patients received two cycles of bolus 5-FU-based systemic chemotherapy followed by pelvic radiation therapy with chemotherapy and two more cycles of the same systemic chemotherapy. Chemotherapy was either 5-FU alone, 5-FU with leucovorin, 5-FU with levamisole, or 5-FU with leucovorin and levamisole.. With a median follow-up duration of 48 months, there is no statistically significant advantage to any of the treatment regimens compared with bolus 5-FU alone. There is evidence of increased gastrointestinal toxicity with the three-drug combination compared with bolus 5-FU alone. Statistical analysis suggests it is very unlikely that either levamisole-containing combination will be shown to be of value with further follow-up evaluation.. There is no evidence at present for a beneficial effect of levamisole in the adjuvant treatment of rectal cancer. Definitive evaluation of the effect of the addition of leucovorin to 5-FU and pelvic radiation will require further follow-up evaluation.

Topics: Adenocarcinoma; Adjuvants, Immunologic; Adult; Aged; Agranulocytosis; Antidotes; Antimetabolites, Antineoplastic; Cause of Death; Chemotherapy, Adjuvant; Combined Modality Therapy; Diarrhea; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Levamisole; Male; Middle Aged; Postoperative Period; Prospective Studies; Rectal Neoplasms; Survival Rate; Treatment Outcome

A randomized comparative study of surgical adjuvant chemotherapy using dl-leucovorin (dl-LV) and 5-fluorouracil (5-FU) (FL-therapy) with CDDP, 5-FU, and dl-LV (PFL-therapy) was conducted. The following were the administration schedules: Arm A was 13 mg/m2 of CDDP, 300 mg/m2 of 5-FU, and 30 mg/body of dl-LV for 5 consecutive days and arm B was 300 mg/m2 of 5-FU and 30 mg/body of dl-LV for 5 consecutive days. Both regimens were followed by biweekly administration of the same dose of dl-LV and 5-FU in outpatients. Arm A was started at the 26th postoperative day and arm B at the 21st day on average. Some 26 cases composed of 11 cases of arm A and 15 cases of arm B completed the administration schedules. Only one case in arm A was complicated by local recurrence around 35 months after operation. Major toxicities were anorexia and neutropenia. Both toxicities were seen more in arm A than in arm B, showing complete recovery in all cases. These data suggest that PFL-therapy and FL-therapy seem to be possible and promising surgical adjuvant therapies for advanced colorectal carcinoma.

Topics: Adenocarcinoma; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Colonic Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neutropenia; Rectal Neoplasms; Survival Rate

The present study compared the effects of sequential methotrexate and fluorouracil followed by leucovorin rescue (MFL), as an adjuvant chemotherapy versus a combination of tegafur (UFT) and mitomycin C (MMC), on patient survival and recurrence after surgery for colorectal carcinoma.. Between January 1990 and December 1995, a total of 46 patients with advanced colorectal cancer were treated postsurgically by adjuvant chemotherapy using MFL or UFT-MMC. Surgical treatment was performed according to standardized procedures for radical resection of colorectal cancer. The patients were stratified into two groups after surgery. The MFL regimen consisted of MTX (100 mg/m2) and 5-FU (600 mg/m2) at hour 24, followed by leucovorin rescue. The UFT-MMC regimen consisted of MMC (12 mg/m2) intraoperatively and MMC (6 mg/m2) ever other week after surgery for 2 months and oral UFT (375 mg/m2/day), a combination of tegafur and uracil in a molar ratio of 1:4, was continued for 3 years or longer depending on the patients tolerance.. The overall survival rates after surgery was significantly (P < 0.05) higher in the MFL than the UFT-MMC group. Recurrence rates were significantly lower in the MFL than the UFT-MMC Group, especially for liver recurrence. Disease-free survival was significantly (P < 0.05) higher in the MFL than the UFT-MMC group.. The present results demonstrated the superiority of MFL therapy for improving postsurgical survival in patients with advanced colorectal cancer, in particular for those patients with a high risk of recurrence following potential curative resection.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colonic Neoplasms; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Fluorouracil; Humans; Leucovorin; Male; Methotrexate; Mitomycin; Postoperative Period; Rectal Neoplasms; Survival Rate; Tegafur; Uracil

Several trials performed in the United States and Europe have demonstrated the efficacy of UFT (uracil and tegafur in a 4:1 molar combination) with oral leucovorin in the treatment of several tumor types, but particularly for advanced colorectal cancer. Phase III studies are under way in the United States to determine whether the combination of UFT with oral leucovorin is as effective as standard treatment, not only in the advanced setting but also in the adjuvant arena as well. This study is an open-label phase I trial to determine the safety of UFT and leucovorin, both given orally three times daily during concurrent fixed doses of pelvic radiotherapy, and to determine the safety of UFT plus oral leucovorin administration after pelvic radiotherapy, chemotherapy, and surgery. Standard treatment at M. D. Anderson Cancer Center for patients with T3, T4, and/ or > N1 rectal carcinoma is a preoperative continuous-infusion of fluorouracil (5-FU) with radiation therapy followed by four courses of 5-FU/ leucovorin postoperatively. Data suggest that UFT and leucovorin may offer a well-tolerated, fully oral treatment option that could be more convenient for patients. The trial presented herein provides data relative to the feasibility of preoperative oral UFT and leucovorin chemotherapy given during radiation therapy, and oral UFT and leucovorin chemotherapy following surgery in the treatment of patients with rectal cancer. This study is anticipated to serve as a pilot to develop an investigational treatment arm for a randomized trial of preoperative treatment of patients with rectal cancer.

Topics: Antidotes; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Drug Combinations; Feasibility Studies; Fluorouracil; Humans; Leucovorin; Radiotherapy Dosage; Rectal Neoplasms; Tegafur; Uracil

A previous phase I trial in 14 pretreated patients with progressive advanced colorectal cancer demonstrated 750 mg/m2 to be the maximum tolerable dose of 5-fluorouracil (5-FU) administered as a five-day continuous infusion modulated by short infusions of 100 mg/m2 folinic acid twice daily. The dose-limiting toxicities were hand-foot syndrome and severe mucositis. A response rate of 21% and 50% stable disease could be achieved. In order to determine the effectiveness and tolerability, we initiated a multicenter phase II trial applying a 650 mg/m2 recommended dose of 5-FU and 100 mg/m2 folinic acid twice daily every three weeks.. From January 1994 to July 1996, 88 advanced and progressive colorectal cancer patients either previously treated with a bolus schedule of 5-FU and folinic acid (34 patients) or without (54 patients) previous chemotherapy were included in this trial.. In the group of previously treated patients, therapy led to 6% (2 of 34 patients) remissions while stable disease could be observed in 68% (23 of 34 patients) of the patients. The median survival time was 14 months. The main toxicity was mucositis grade 3 in 15% of the previously treated patients and 10% in the nonpretreated patients. In the population of nonpretreated patients, the overall response rate was 15% (eight of 54 patients) and stable disease could be induced in 67% (36 of 54 patients). The median survival time was 13.7 months.. This regimen is an active second-line therapy in advanced colorectal cancer with minimal toxicity, thus preserving the quality of life during palliative chemotherapy. Antitumor activity in previously untreated patients does not seem superior to that obtained with weekly regimens applying 24- or 48-hour continuous infusions of 5-FU and folinic acid.

Topics: Adult; Aged; Antidotes; Antimetabolites, Antineoplastic; Colonic Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Quality of Life; Rectal Neoplasms; Treatment Outcome

To investigate if double modulation of fluorouracil (5-FU) with leucovorin (folinic acid [FA]) and interferon alfa-2b (IFN 2b) improves responses and survival in comparison to single modulation of 5-FU with FA.. One hundred six patients with histologically confirmed advanced colorectal cancer, measurable disease, and without previous chemotherapy were prospectively randomized into two groups. Patients in group A received 5-FU 450 mg/m2 as an intravenous bolus in the midinfusion of FA weekly. FA was given at a dose of 200 mg/m2 in 500 mL 0.9% normal saline solution in 2-hour infusion. Patients in group B received exactly the same regimen plus IFN 2b 5 million units subcutaneously three times weekly.. All patients were well balanced in both groups regarding age, sex, performance status, number, and site of metastasis. One hundred two patients were assessable. All patients have died. There was no difference in response between the two groups (7.8% v 9.8%). Median survival was 10.1 months in group A, and 7.2 months in group B (P = .00189). Median time to progression was 8.4 and 5.2 months, respectively (P = .00196). Overall, better performance status and older age had a positive impact on survival. Toxicity was the most important and catastrophic aspect of this study. Patients who received IFN 2b had significantly worse anemia, neutropenia, diarrhea, anorexia, weight loss, flu-like syndrome, and psychological reactions.. Based on this final analysis, the addition of IFN 2b to the combination of 5-FU and FA enhances toxicity and contributes to decreased survival.

Topics: Adult; Aged; Antidotes; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Disease-Free Survival; Female; Fluorouracil; Humans; Interferon alpha-2; Interferon-alpha; Leucovorin; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Rectal Neoplasms

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Colonic Neoplasms; Drug Resistance, Neoplasm; Drug Therapy, Combination; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Rectal Neoplasms

A total of 40 primary and 20 recurrent adenocarcinomas of the rectum were treated. Intraoperative radiation therapy was combined with pre- or postoperative irradiation and 5-FU and leucovorin treatment. An abdomino-perineal excision was performed in 32 and an anterior resection in 26 cases. A Hartmann's procedure was performed in two patients. Forty-two tumours were completely resected. Residual disease was microscopically detectable in 10 cases. In eight patients, tumour residual was evident macroscopically. Postoperatively, wound infection was observed in six and anastomotic dehiscence in four cases. After a follow-up of 20 months, 46 patients revealed no evidence of disease. Local recurrences and distant metastases were detected in two patients each. Ten patients died of their disease.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Clinical Protocols; Female; Fluorouracil; Humans; Intraoperative Care; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Radiotherapy, Adjuvant; Rectal Neoplasms; Treatment Outcome

Thirty previously untreated patients with metastatic colorectal carcinoma were randomized as part of two multicenter Phase III trials. Twenty-two patients were randomized to receive either 5-fluorouracil (5-FU)/interferon alfa-2A (IFN-alpha) or 5-FU/leucovorin (11 patients in each arm). Eight patients were randomized to receive 5-FU/IFN-alpha or 5-FU alone (4 patients in each arm).. Twenty-three patients (13 patients treated with 5-FU/IFN-alpha and 10 patients treated with 5-FU/leucovorin or 5-FU alone) were evaluated regularly for response by computed tomography (CT) scans of the abdomen when treatment began and then every 6-8 weeks.. Incidentally, four patients developed hepatic steatosis during treatment with IFN-alpha and 5-FU. The diagnosis was based on a decreased CT value of the liver parenchyma by repeated CT scans of the abdomen during treatment, and this diagnosis was verified histologically by liver biopsy. There was no relationship to cumulative IFN-alpha or 5-FU dose. Based on posttreatment CT scans, the liver parenchyma changes were reversible after therapy was stopped, and there were no significant clinical sequelae. No patients treated with 5-FU/leucovorin or 5-FU alone experienced a decreased CT value of the liver parenchyma.. Hepatic steatosis was been observed in approximately 30% of patients treated with IFN-alpha and 5-FU. The hepatic changes were fully reversible after the treatment was stopped. Recognition of this condition is important to prevent a patient from being labeled as having progressive hepatic metastases.

Topics: Adenocarcinoma; Colonic Neoplasms; Fatty Liver; Female; Fluorouracil; Humans; Interferon alpha-2; Interferon-alpha; Leucovorin; Liver Neoplasms; Male; Middle Aged; Recombinant Proteins; Rectal Neoplasms; Tomography, X-Ray Computed

To determine the relationship between acute gastrointestinal (GI) toxicity during the combined modality segment and the volume of small bowel in the pelvic radiation field in patients who receive either preoperative or postoperative therapy for rectal cancer.. The patient population was derived from four consecutive phase I dose-escalation trials. Combined modality therapy included fluorouracil (5-FU), leucovorin ([LV] bolus daily x 5, days 1 and 29), and pelvic radiation.. Twenty patients who received postoperative therapy had a larger volume of small bowel in the pelvic radiation field as compared with 60 who received preoperative therapy (462 +/- 129 v 212 +/- 44 cm3, P = .002). The most significant relationship between acute GI toxicity and volume of small bowel was seen in 12 patients who were treated on the preoperative sequential low-dose LV trial, all of whom received the maximum-tolerated dose (MTD) of 5-FU. The volume of small bowel in patients who experienced grade 3+ toxicity was 731 +/- 274 cm3, as compared with 145 +/- 58 in those who experienced grade 0 to 2 toxicity (P = .005). Likewise, logistic regression analysis showed that 26 patients who received the MTD of 5-FU had the most significant association between GI toxicity and volume of small bowel (P = .036).. Our data suggest that the volume of small bowel in the pelvic radiation field may be dose-limiting in the delivery of high-dose 5-FU when combined with LV and radiation therapy.

Topics: Adenocarcinoma; Combined Modality Therapy; Fluorouracil; Humans; Intestine, Small; Leucovorin; Neoplasm Recurrence, Local; Rectal Neoplasms; Regression Analysis

We report the local control and survival in a previously reported phase I dose escalation trial of combined postoperative 5-FU, high dose leucovorin (LV), and sequential radiation therapy followed by maintenance LV/5-FU for the treatment of patients with clinically resectable rectal cancer. Following surgery for stages T3-4N0-2M0 primary (21) or recurrent (4) rectal cancer, 25 patients received 5-FU/LV x 1 cycle. Radiation therapy (5040 cGy) began on day 8. A second cycle of 5-FU/LV was given concurrent with the fourth week of radiation. Patients received an additional 10 cycles of LV/5-FU. The median follow-up was 40 months (range 18-52). The incidence of grade 3+ acute toxicity in the 9 patients who received the recommended dose of 5-FU was 44%. The local failure rate was 28%. Abdominal and distant failure rates were 24%. The 3-year actuarial disease-free survival was 74% and the overall survival was 80%. Our preliminary data reveal reasonable local control and survival rates. However, further follow-up is needed to assess our results at 5 years. Postoperative combined modality therapy with high-dose LV may be an option for the adjuvant treatment of patients with resectable rectal cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Rectal Neoplasms; Survival Analysis

Topics: Adult; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Methotrexate; Middle Aged; Rectal Neoplasms; Retrospective Studies

Exogenous leucovorin is a source of reduced folate which enhances the inhibition of thymidylate synthase that results from 5-fluorouracil (5-FU) administration. Extracellular reduced folate concentrations of 1 microM have been reported to yield maximal enzyme inhibition in several cell lines treated with 5-FU in vitro. Clinical studies indicate that low doses of leucovorin have equivalent efficacy to higher doses in successfully modulating 5-FU in the treatment of colorectal cancer. Based on pharmacokinetics at higher doses, steady-state total plasma reduced folate concentrations of 1 microM would be expected from the administration of leucovorin 50 mg/m2 by 24 h infusion. This dose was admixed with 5-FU 2300 mg/m2 and administered by 24 h-infusion weekly to 38 patients with advanced colorectal cancer, of whom 32 are evaluable for response. Disease sites included liver (33 patients), lung (12 patients), and bone (4 patients). Toxicity was mild to moderate, except for grade 3 diarrhea in 5 patients, and chest pain in 2 patients. Among the 32 evaluable patients, there were 14 partial remissions for a total response rate of 44% (95% confidence interval 27-61%). The median duration of response was seven (range 1 to 20+) months, and median duration of survival 16 months. These results support the use of low doses of leucovorin to modulate weekly infusional 5-FU in colorectal cancer, and provide a basis for the integration of this regimen with other modulators of 5-FU.

Topics: Adult; Aged; Antidotes; Antimetabolites, Antineoplastic; Colonic Neoplasms; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Rectal Neoplasms

Based on experimental findings suggesting that 5-fluorouracil (FUra) may have different mechanisms of action depending on the schedule of administration, we generated the hypothesis that biochemical modulation of this fluoropyrimidine should be schedule specific. We thus tested the activity of a hybrid regimen consisting of two biweekly cycles of FUra bolus (600 mg/m2) modulated by pretreatment (24-h interval) with methotrexate (200 mg/m2), alternating with a 3-week continuous infusion of FUra (200 mg/m2/day) modulated by low-dose (6S)leucovorin (20 mg/m2 bolus weekly). Thirty-three consecutive patients with advanced measurable colorectal cancer and no prior therapy for metastatic disease entered the study from February 1992 to August 1993. They were treated with two biweekly cycles of FUra bolus (600 mg/m2) preceded by (24-h interval) methotrexate (200 mg/m2), alternating with a 3-week continuous infusion of FUra (200 mg/m2/day) modulated by low-dose (6S)leucovorin (20 mg/m2 bolus weekly). The median Eastern Cooperative Oncology Group performance status was 1; the liver was the only metastatic site in 17 patients. Treatment outcome was evaluated by computed tomographic scan in all patients, except for two. Three complete and 13 partial responses were obtained among these 33 patients (response rate, 48%; 95% confidence limits, 31-66%). Performance status (Eastern Cooperative Oncology Group) influenced clinical response. The combined complete response and partial response rate was 69%, 33%, and 25% in patients with an Eastern Cooperative Oncology Group performance status of 0, 1, and 2, respectively (chi2, 4.6, P = 0.032, two-tailed Mantel test for trend). After a median follow-up time of 26 months, 10 patients are still alive. The median progression-free survival and overall survival were 9.5 and 20.2 months, respectively. No toxic deaths or grade 4 toxicity occurred. The incidence of grade 3 toxicity per patient in any cycle was: mucositis 6%, diarrhea 3%, and vomiting 3% for the bolus part and 21%, 3%, and 6%, respectively, for the continuous infusion part of the regimen. Hand-foot syndrome occurred in 27% of the patients treated with the continuous infusion regimen.

Topics: Adult; Aged; Antidotes; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Disease-Free Survival; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Rectal Neoplasms

We previously reported positive results to Tegafur-Uracil (UFT) chemotherapy in a group of patients with advanced rectal cancer. We have continued the study and now report the effectiveness of UFT plus folinic acid (FA) in 52 patients with advanced rectal cancer. The therapeutic schedule was UFT, 600 mg/m2/day x 14 days p.o. + FA, 90 mg/m2/day x 14 days p.o. Fifty-two out of a total of 56 patients were evaluated for response and toxicity. A higher incidence of positive responses in patients without previous chemotherapy was appreciated. Twenty-one of the 52 evaluated patients showed a partial response (PR). Responses were strongly correlated with previous chemotherapy (14/20; 70% PR of cases without previous chemotherapy vs 7/32; 22% of cases with previous chemotherapy). All responding patients came forward with a median time to progression of 8.2 months (19.6 months for patients without previous chemotherapy vs 7.7 months for patients with previous chemotherapy, P < 0.01). We concluded that the UFT plus FA could be a treatment of choice for patients with advanced rectal cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Humans; Leucovorin; Leukopenia; Middle Aged; Nausea; Rectal Neoplasms; Survival Rate; Tegafur; Uracil; Vomiting

In advanced colorectal cancer the addition of folinic acid (FA) has been shown to lead to increased activity, at least in terms of response rate, in comparison with 5-fluorouracil (5FU) alone. Similarly, interferon-alpha (IFN) is able to potentiate 5FU, although high doses cause heavy toxicity. Given the different mechanisms of action of the two agents, the double modulation of 5FU deserves clinical evaluation. In a multicenter study (involving both primary care and referral institutions) 63 patients with advanced colorectal cancer, previously untreated with chemotherapy, received, in an outpatient setting, FA (200 mg/m2 i.v. bolus) + 5FU (400 mg/m2 i.v. in 15 min) for 5 consecutive days every 4 weeks + IFN 3 x 10(6) U on alternate days, starting 1 week before chemotherapy. During the 5 days of 5FU + FA, IFN was administered daily. The antitumour activity, the impact on response duration and survival and toxicity of the combination were evaluated according to WHO criteria. Of the 63 enrolled patients, 56 were evaluable: there were 2 complete responses (3%) and 13 partial responses (21%), giving an objective response rate of 24% (95% confidence interval 13-35%); no change was observed in 17 cases and progressive disease in 24. Median duration of response was 9 months and median survival (all patients) 13 months. Toxicity was acceptable, even though 4 patients presented reversible grade 4 side-effects (2 mucositis and 2 diarrhoea). With this schedule and these doses, addition of IFN did not lead to any increase in the activity of 5FU + FA. In colorectal cancer, further clinical studies with these drugs should be based on a deeper experimental knowledge of their mechanisms of interaction.

Topics: Adult; Aged; Colonic Neoplasms; Drug Administration Schedule; Drug Synergism; Female; Fluorouracil; Humans; Interferon alpha-2; Interferon-alpha; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Recombinant Proteins; Rectal Neoplasms

The study was performed to evaluate the feasibility of combining leucovorin (LV) with 5-fluorouracil (5FU) and radiation therapy as adjuvant treatment for high-risk rectal carcinoma.. Twenty-five patients with histologically proven adenocarcinoma of the rectum, at high-risk of recurrence after potentially curative resection (T3 NO, T and N1-2; MO), received 5FU (370 mg/m2) and 6S-LV (100 mg/m2) on days 1-5, 4 and 8 weeks after surgery. On treatment day 64, radiotherapy on the pelvis (50 Gy) was initiated. Finally, three further courses of 5FU/LV were given at intervals of 4 weeks beginning 28 days after the completion of radiotherapy.. The treatment was generally well tolerated. We observed only 2 cases of grade III toxicity (diarrhea) during the third cycle of chemotherapy. No severe complications were recorded following the use of radiotherapy. The mean overall 5FU dose intensity was 92%. After a median follow-up of 24 months, 4 patients had relapsed (liver, lung, and pelvis, 2 cases).. The association of LV to 5FU and radiation therapy seems to be feasible, with acceptable toxicity. The advantage of this combination, in terms of recurrence rate and survival with respect to 5FU/radiotherapy alone, will have to be evaluated in randomized trials.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Pilot Projects; Radiotherapy Dosage; Radiotherapy, Adjuvant; Rectal Neoplasms; Treatment Outcome

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Rectal Neoplasms

N-(phosphonacetyl)-L-aspartic acid (PALA) inhibits the enzyme L-aspartic acid transcarbamoylase (ATCase) which is important in de novo pyrimidine synthesis. Low dosages of PALA modulate the in vitro activity of 5-fluorouracil (5-FU) and PALA (250 mg/m2) inhibits pyrimidine synthesis in patients. PALA (250 mg/m2 day 1) was combined with an established 5-FU/folinic acid (FA) regimen [FA (200 mg/m2 over 2 h days 2 + 3) and bolus and 22 h infusional 5-FU (300-500 mg/m2 days 2 + 3)] without the need for dose reduction of 5-FU or FA. 35 patients were entered. Treatment was well tolerated; 4/27 patients experienced > or = ECOG grade 3 toxicity at full 5-FU dosage (500 mg/m2 bolus/infusion). However, the response rate in 33 evaluable patients was only 6.1% [95% confidence intervals (C.I.) 0.2-21.8%]. Median response duration was short (4 months, 95% C.I. 3-6 months) and overall median survival was 10 months (95% C.I. 7-16 months). Although PALA (250 mg/m2) can be combined with full dosage 5-FU/FA, the combination has poor activity in colorectal cancer.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Aspartic Acid; Colonic Neoplasms; Disease Progression; Dose-Response Relationship, Drug; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Phosphonoacetic Acid; Rectal Neoplasms

Fifty patients were randomized to receive adjuvant intraperitoneal 5-fluorouracil (5-FU, 500 mg/m2/day) and intravenous leucovorin (60 mg/m2/day) and 51 to receive placebo after curative surgery for colorectal cancer. Treatment started on the day after surgery and continued for 6 days. One case of stomatitis, one of leucopenia and one case of abnormal liver function tests were the only chemotherapy-related toxic effects. From the second day of treatment, pain during intraperitoneal infusions occurred more frequently in the 5-FU group, although statistical significance was only attained on day 2 (P < 0.05). The groups did not differ substantially regarding any other adverse effects, the incidence of surgical complications, second laparotomies, time from surgery to discharge, or premature treatment terminations. The postoperative course after intraperitoneal 5-FU and intravenous leucovorin was thus not more complicated than that in patients treated with placebo. The tolerance was acceptable and chemotherapy-related toxicity was rare. Thus important prerequisites exist for more widespread use of the present regimen in order to evaluate its impact on survival.

Topics: Adult; Aged; Chemotherapy, Adjuvant; Colonic Neoplasms; Female; Fluorouracil; Humans; Infusions, Parenteral; Leucovorin; Male; Middle Aged; Rectal Neoplasms

Because of experimental and preliminary clinical evidence that additional modulation of the biochemical pharmacology and cytotoxicity of 5-fluorouracil (5-FU) and leucovorin (LV) may be possible by combination of these agents with cisplatin (CDDP), the authors undertook a prospective randomized trial in patients with colorectal cancer.. Between 1989 and 1992, 138 patients with advanced measurable colorectal cancer previously unexposed to chemotherapy were randomly assigned to treatment with either 5-FU (425 mg/m2) and LV (20 mg/m2) for 5 days, or the combination of 5-FU and LV in the same daily dose plus cisplatin (20 mg/m2), each drug given for 4 consecutive days. In both treatment arms, courses were administered every 28 days, if toxicity allowed, for a total of 6 months or until evidence of tumor progression.. The overall responses (complete and partial response) were 19% and 28% for the 5-FU/LV and the 5-FU/LV/CDDP treatment arms, respectively. Although the three-drug combination appeared superior to 5-FU/LV for time to progression or death (8.5 versus 5.2 months; P = 0.042), there was no evidence that the adoption of cisplatin will translate into a definite survival advantage. A comparative analysis of the toxicities experienced by the patients in the two treatment groups showed a comparable rate, although severe side effects (P < 0.05), specifically stomatitis (P = 0.013), were noticed more frequently in patients treated with 5-FU/LV for 5 days.. These results suggest that the therapeutic index of 5-FU/LV in metastatic colorectal cancer may be improved with the addition of cisplatin. However, the somewhat better therapeutic activity and lower incidence of severe gastrointestinal side effects have to be weighed against additional pharmaceutical charges and the need for a more intense antiemetic regimen.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Cisplatin; Colonic Neoplasms; Diarrhea; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Neoplasm Recurrence, Local; Prospective Studies; Rectal Neoplasms; Remission Induction; Stomatitis; Survival Rate

A Phase I trial was performed to determine the maximum tolerated dose of concurrent preoperative radiation therapy (5040 cGy) and 2 cycles (bolus daily times 5) of 5-fluorouracil (5-FU) and low-dose leucovorin (LV) (20 mg/m2), followed by surgery and 10 cycles of postoperative 5-FU/LV in patients with primary or recurrent rectal cancer.. Twenty-four patients were entered into the study. Preoperatively, the initial dose of 5-FU was 325 mg/m2. 5-FU was escalated 50 mg/m2, while the dose of LV and radiation therapy remained constant. Chemotherapy and radiation began concurrently on day 1. The postoperative chemotherapy was not dose escalated; 5-FU, 425 mg/m2, and LV, 20 mg/m2. The median follow-up was 10 months (range, 4-19 months).. The resectability rate with negative margins in the 23 patients who underwent surgery was 100%. One patient refused surgery. The pathologic complete response rate was 13% (3 of 23). An additional four patients had negative nodes and a microscopic foci of tumor in the bowel wall. Therefore, the total clinical complete response rate was 30% (7 of 23). The maximum tolerated dose of 5-FU for the preoperative combined modality segment was 375 mg/m2; therefore, the recommended Phase II dose level is 325 mg/m2. The incidence of Grade 3+ toxicity for the 22 patients treated at the recommended 5-FU dose level (325 mg/m2) during the preoperative combined modality segment was as follows: diarrhea, 14%; erythema, 5%; hematologic, 10%; and total, 18%. The median nadir counts were leukocyte count, 3.7 (range, 1.5-5.9); hemoglobin count, 12.2 (range, 10.2-14.3); and platelet count (times 1000), 165 (range, 92-237).. With this regimen, the recommended doses of chemotherapy in the combined modality segment are slightly higher than those recommended in arm 2 of the Intergroup postoperative adjuvant rectal trial 0114. This regimen will serve both as the preoperative arm of the Intergroup randomized trial of preoperative versus postoperative combined modality therapy for resectable rectal cancer (INT R9401) as well as the basis for the combined modality segment of NSABP RO-3.

Topics: Adenocarcinoma; Adult; Aged; Brachytherapy; Combined Modality Therapy; Drug Administration Schedule; Fluorouracil; Humans; Leucovorin; Middle Aged; Postoperative Care; Preoperative Care; Radiotherapy, High-Energy; Rectal Neoplasms

To compare the length of survival and quality of life in patients given combination chemotherapy in addition to supportive care and in patients given only supportive care.. Randomised study.. Gastrointestinal oncology departments.. 40 previously untreated patients with histologically confirmed, measurable colorectal cancer that was locally recurrent or metastatic.. Patients were allocated randomly to receive chemotherapy or only supportive care in a ratio of 2:1 according to performance status, metastatic disease of the liver, and weight loss in the six months before entering the study. Chemotherapy consisted of four week cycles of intravenous leucovorin (200 mg/m2/day) followed by 5-fluorouracil (550 mg/m2/day) and cisplatin (20 mg/m2/day), each drug being given on the first four days of the cycle.. Length of survival and quality of life score with an optimised functional living index-cancer scale.. Overall survival was significantly longer for patients given chemotherapy (11.0 months) than for those receiving supportive care alone (5.0 months; p = 0.006). Despite common association of chemotherapy with mild to moderate gastrointestinal symptoms, there was no significant difference between the two groups in global or subgroup quality of life scores. In patients with abnormal scores before treatment, quality of life seemed better in the chemotherapy arm.. In this sample of patients with disseminated colorectal cancer the chemotherapy regimen was an effective form of palliative treatment.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Colonic Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Palliative Care; Prognosis; Quality of Life; Rectal Neoplasms; Social Support

Prolonged infusional 5-fluorouracil (5-FU) and bolus 5-FU modulated by leucovorin are associated with higher response rates than bolus 5-FU alone. Cisplatin enhances 5-FU cytotoxicity in some preclinical models.. The authors tested the feasibility of combining concurrent infusional leucovorin (500 mg/m2/d) with protracted infusional 5-FU (200 mg/m2/d) and weekly bolus cisplatin (20 mg/m2) in 22 patients with metastatic colorectal cancer.. Four partial responses (PR) were noticed among 21 evaluable patients (19%). The median time to treatment failure and median survival were 6 months and 11 months, respectively. All but two patients required 5-FU dose reduction after a median of 2 weeks because of mucositis. However, severe mucositis and diarrhea occurred in only 18% and 5% of the patients, respectively. Palmar-plantar erythrodysesthesia of mild to moderate severity occurred in 55% of patients. Megaloblastic changes were evident in the peripheral blood during therapy, and may reflect prolonged DNA-directed toxicity of 5-FU. The median tolerated dose level of 5-FU was 113 mg/m2/d (range, 64-150 mg/m2/d). Mean steady-state plasma concentrations (Cpss) of 5-FU appeared to increase linearly from 0.19 microM to 0.39 microM over the dose range 64 to 200 mg/m2/d. Patients with grade 2 gastrointestinal toxicity had significantly higher 5-FU Cpss than patients with grade 0 or 1 toxicity.. The early onset of toxicity with this regimen of protracted infusional 5-FU/high-dose leucovorin and weekly cisplatin required marked attenuation of the 5-FU dose intensity, and the results were no better than that expected with infusional 5-FU alone.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Colonic Neoplasms; Dose-Response Relationship, Drug; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Rectal Neoplasms; Survival Analysis; Treatment Failure

Combined modality treatment for cancer of the rectum has been shown to reduce recurrences and improve overall survival. We wished to find out if we could safely give concurrent radiotherapy and 5-fluorouracil (5-FU) modulated by leucovorin (LV) in 3 settings: pre-operatively, adjuvantly and in recurrent disease. A total of 39 patients were treated, 11 preoperatively, 17 adjuvantly and 11 with recurrent disease. There were 26 males and 13 females with a median age of 64 years. The median radiotherapy (RT) dose was 45 Gy/25 fractions/1.8 Gy per fraction (range 25-63 Gy). Chemotherapy consisted of LV 80 mg/m2 i.v. infusion over 1.5 hours followed by 5-FU 400 mg/m2 i.v. bolus, both given once a week. The median number of cycles was 8 (range 3-12). Diarrhoea was the main toxicity, and was encountered in 30 patients (77%): grade 1 in 3 (8%), grade 2 in 12 (30%), grade 3 in 11 (28%), and grade 4 in 4 (10%). This required 18 (46%) patients to have modifications to their RT (20% had breaks and 26% ceased at doses < 45 Gy). Nine patients (23%) had modifications in the chemotherapy (10% had breaks and 13% received < 6 cycles). Encouraging responses were seen in the preoperative setting. Concurrent RT and 5-FU/LV, as given in this schedule, results in an unacceptable incidence of diarrhoea, limiting both the total dose of RT and chemotherapy that can be delivered, particularly in patients who have had previous surgery.

Topics: Adenocarcinoma; Aged; Combined Modality Therapy; Diarrhea; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Pelvis; Radiotherapy; Radiotherapy Dosage; Rectal Neoplasms; Survival Rate

Failure rate of colorectal cancer after surgical resection remains around 50% and adjuvant treatments are clearly required.. All patients with serosal involvement and/or lymph node metastases are at risk of recurrence (Dukes-Astler Coller B2, C1, C2). For thirty years many randomized trials testing chemotherapy and radiation therapy (rectum) have been conducted and some have demonstrated some kind of significant activity. We have analysed these trials and proposed with the EORTC GI tract cooperative group a new prospective randomized trial (40911).. In colon cancer, five trials have tested single agent systemic chemotherapy and failed to demonstrated a significant increase in survival. Four trials have tested systemic chemotherapy with 5-FU + MeCCNU +/- oncovin and only one (NSABP COI ant ROI) has demonstrated some significant benefit in term of survival. The combination of 5-FU + levamisole has been tested in 4 trials; in two there was a trend in favor of the treated group and in the intergroup trial there was a very significant increase in survival for Duke C patients. Six trials have tested the efficacy of post-operative local chemotherapy (intraportal); 3 demonstrated a significant increased survival and 2 a decrease in hepatic recurrence rate. Among the ongoing trials the EORTC 40911 aims to evaluate the interest of combining systemic chemotherapy (5-FU + levamisole or 5-FU + 1 folinic acid) to postoperative local chemotherapy (intraportal or intraperitoneal). In rectal cancer, preoperative radiation therapy significantly decreases the local recurrence rate, more than post-operative radiation therapy. The combination of post-operative radiation therapy with chemotherapy increases significantly survival rate. Presently patients with mobile rectal tumor located at the middle or the upper part of the rectum should be when possible randomized in trials such as the EORTC 40911. Concerning patients with large tumor located at the inferior part of the rectum new trials combining preoperative radiotherapy chemotherapy will be initiated.. Some randomized trials using polychemotherapy have resulted in increasing survival rate in adjuvant setting regarding patients with colorectal cancer. New trials have been initiated to further improve these encouraging results.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colorectal Neoplasms; Combined Modality Therapy; Female; Fluorouracil; Humans; Infusions, Intravenous; Infusions, Parenteral; Leucovorin; Levamisole; Male; Portal Vein; Rectal Neoplasms; Risk Factors

In three consecutive phase II trials, 5-fluorouracil (5FU)-low dose leucovorin (20 mg/m2/day) was delivered in two 5-day courses during the first (d1 to d5) and the last (d29 to d33) week of a limited pelvic irradiation (45 Gy, 5 weeks, 25 fractions) in patients with locally extended rectal cancer. The three trials differed only by the 5FU dose in the chemotherapy (CT) schemes. In trial 1 (first CT course 5FU dose 425 mg/m2/day, second CT course 370 mg/m2/day), 16 patients were included. 5 patients suffered a grade 3+ toxicity and the compliance was 63%. In trial 2 (first and second CT course 5FU dose 370 mg/m2/day), 53 patients were included. 5 patients suffered a grade 3+ toxicity. The compliance was 94%. In the trial 3 (first and second CT course 5FU dose 350 mg/m2/day), 16 patients were included. 1 patient suffered a grade 3 toxicity and the compliance was 100%. The overall response rate (complete and partial responses) of local disease and distant metastasis were 87 and 7%, respectively. 43 patients were operated on after a mean delay of 8 weeks. Among the 41 macroscopic complete resections, 6 (14.6%) were sterilised and 12 (29.3%) were classified Asler-Coller A/B1. Regression curve analysis using either grade 3+ toxicity or incomplete treatment as an end point against the 5FU dose indicates that a 350 mg/m2/day 5FU dose is advisable for a phase III adjuvant multicentre trial.

Topics: Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Patient Compliance; Rectal Neoplasms; Treatment Outcome

Leucovorin, given usually by i.v. injection or orally changes to 5, 10-methylene tetrahydrofolate in tumor as well as normal cells. And in normal FdUMP, an active metabolite of 5-FU, binds tightly to thymidylate synthase in the presence of cofactor, 5, 10-methylene tetrahydrofolate. This interaction leads to potentiate the cytotoxic effect of 5-FU by prolonged inhibition of thymidylate synthase. Phase I study using l-leucovorin (l-LV), an active form of leucovorin, combined with 5-FU, was conducted. In the weekly schedule, 5-FU was fixed to 600mg/m2, and l-LV dose was escalated from 125 mg/m2 to 250mg/m2, if toxicity was acceptable. On the other hand, in the five consecutive-day schedule, 5-FU was fixed to 370mg/m2 and l-LV was escalated from 25mg/m2 to 50mg/m2, 100mg/m2 and 200 mg/m2. l-LV 10mg/m2 was tested as reference. On weekly schedule of l-LV 250mg/m2, grade III diarrhea was seen in 2 cases and grade IV leucopenia was seen in one. In five consecutive-day schedule, at each dose of l-LV, stomatitis, nausea plus vomiting, anorexia, anemia and leucopenia were seen. However, the increase of toxicities were not seen by dose escalation of l-LV. Then, we have been conducted a randomized early phase II study using 250 mg/m2 of l-LV weekly (arm A) and 100mg/m2 (arm B) or 10mg/m2 (arm C) of l-LV for 5 consecutive days in gastric and colorectal cancer by multicenter cooperative study. Plasma concentrations of l-LV were maintained > 10(-5) mol/L for over 5 hrs. after 2 hrs. infusion of 250 mg/m2 of l-LV and for over one hr. after a rapid injection of 100mg/m2 of l-LV.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Rectal Neoplasms; Stomach Neoplasms

We performed a Phase I trial to determine the maximum tolerated dose of combined pre-operative radiation (5040 cGy) and 2 cycles (bolus daily x 5) of 5-FU and low dose LV (20 mg/m2), followed by surgery and 10 cycles of post-operative LV/5-FU in patients with unresectable primary or recurrent rectal cancer.. Twelve patients were entered. The initial dose of 5-FU was 325 mg/m2. 5-FU was to be escalated while the LV remained constant at 20 mg/m2. Chemotherapy began on day 1 and radiation on day 8. The post-operative chemotherapy, was not dose escalated; 5-FU: 425 mg/m2 and LV: 20 mg/m2. The median follow-up was 14 months (7-16 months).. Following pre-operative therapy, the resectability rate with negative margins was 91% and the pathologic complete response rate was 9%. For the combined modality segment (preoperative) the incidence of any grade 3+ toxicity was diarrhea: 17%, dysuria: 8%, mucositis: 8%, and erythema: 8%. The median nadir counts were WBC: 3.1, HGB: 8.8, and PLT: 153,000. The maximum tolerated dose of 5-FU for pre-operative combined LV/5-FU/RT was 325 mg/m2 with no escalation possible. Therefore, the recommended dose was less than 325 mg/m2.. Since adequate doses of 5-FU to treat systemic disease could not be delivered until at least 3 months (cycle 3) following the start of therapy, we do not recommend that this 5-FU, low dose LV, and sequential radiation therapy regimen be used as presently designed. However, given the 91% resectability rate we remain encouraged with this approach.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Prospective Studies; Radiotherapy; Rectal Neoplasms

The encouraging results seen in patients who received postoperative combined modality therapy in the adjuvant setting have prompted increased interest in preoperative combined modality therapy for patients with unresectable rectal cancer. The authors report the local control and survival of a previously reported Phase I dose escalation trial of combined preoperative 5-fluorouracil (5-FU), high-dose leucovorin (LV), and sequential radiation therapy followed by postoperative LV-5 FU for the treatment of patients with unresectable rectal cancer.. Twenty patients (13, primary and 7, recurrent disease) received LV-5-FU for one cycle. Radiation therapy (5040 cGy) began on day 8. A second cycle of LV-5-FU was given concurrently with week 4 of radiation. Six patients received intraoperative brachytherapy. Postoperatively, the patients received LV-5-FU. The pathologic complete response rate was 20%, and 89% underwent a complete resection with negative margins.. The crude local failure rate was 26%, and the 3-year actuarial local failure rate was 29% (95% confidence interval [CI], +/- 8.94%). The crude abdominal and distant failure rates were 40% and 30%, respectively. The 3-year actuarial disease-free survival was 64% (95% CI, +/- 6.75%), and the overall survival was 69% (95% CI, +/- 7.65%).. These preliminary data revealed encouraging local control and survival rates. Preoperative combined modality therapy is an attractive approach in patients with unresectable rectal cancer.

Topics: Aged; Brachytherapy; Combined Modality Therapy; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Postoperative Complications; Premedication; Prospective Studies; Radiotherapy Dosage; Rectal Neoplasms; Sigmoid Neoplasms

We conducted a phase I/II trial of 5-fluorouracil (5-FU)/folinic acid (FA) and alpha-2b interferon (IFN) in 43 previously untreated patients with measurable metastatic colorectal cancer. Patients had disease progression prior to therapy consistent of 5-FU 500 mg/m2 (level A) or 600 mg/m2 (level B) as starting dose administered as a 2-hour infusion, FA 200 mg/m2, and alpha-2b IFN 5MU/m2 subcutaneously. All drugs were given on days 1 to 5 and cycles were repeated after 3 to 4 weeks. The aim of the study was to define the maximal tolerable dose (MTD) of 5-FU for this schedule. In the absence of toxicity above MTD, defined as diarrhea and mucositis of World Health Organization grade 2 and leukopenia of World Health Organization, grade 3 5-FU was increased in increments of 100 mg/m2 for further cycles. Twenty-four patients were started on level A; 18 were started on level B. Forty-two patients were evaluable for toxicity, 32 for response. Three of 32 patients achieved a partial response; in 22 of 32 patients, tumor stabilization occurred. Forty percent of patients started on level A developed grade 2 diarrhea; 28% of patients developed grade 2 or 3 mucositis. Of 18 patients on level B, two patients experienced grade 4 mucositis (11%) and grade 3 or 4 diarrhea (11%). One drug-related death in the presence of sepsis occurred. Due to 11% of patients with grade 4 toxicity when started on 600 mg/m2 5-FU and 40% of patients with grade 2 diarrhea when started on level A, MTD as starting dose for 5-FU is 500 mg/m2 as a 2-hour infusion when used in combination with FA and IFN on a day 1 to 5 active schedule. We observed a wide range of 5-FU dose tolerated by individual patients. While some patients experienced severe, mainly gastrointestinal, toxicity on lower levels of 5-FU, others tolerated much higher 5-FU doses (11 patients, 700 mg/m2; 5 patients, 800 mg/m2; and one patient, 900 mg/m2). Our data suggest that double modulation of 5-FU by FA and IFN may not be superior to modulation of 5-FU with either drug alone.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Drug Evaluation; Female; Fluorouracil; Humans; Interferon alpha-2; Interferon-alpha; Leucovorin; Male; Middle Aged; Neoplasm Staging; Recombinant Proteins; Rectal Neoplasms

Interferon has been shown to augment the cytotoxic effects of fluorouracil (5-FU) against colon cancer in vitro and possibly in vivo. Therefore a pilot study was initiated to evaluate the effects of the combination 5-FU/FA/interferon alfa (IFN-alpha) in colorectal adenocarcinomas refractory to first-line therapy with 5-FU/FA. Eleven patients with rectum cancer and four patients with colon cancer were treated according to the following schedule: 9 million units IFN-alpha subcutaneous three times a week; 500 mg/m2 5-FU via an intravenous bolus 1 hour after the initiation of a 2-hour infusion of 500 mg/m2 of FA, once a week. Of 15 patients, one had a minor response, one had a disease stabilization, and three had a mixed response. No complete or partial remissions were seen. Looking at the sensitivity of lung metastases (three of three), the regressions can be explained through the additive effect of IFN-alpha to 5-FU/FA. Although minimal side effects (World Health Organization classification) were observed, most patients experienced a reduction of well-being.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Female; Fluorouracil; Humans; Interferon alpha-2; Interferon-alpha; Leucovorin; Liver Neoplasms; Male; Middle Aged; Recombinant Proteins; Rectal Neoplasms

Modulation of fluorouracil (5-FU) therapy with folinic acid (FA) in advanced colorectal adenocarcinoma produces a doubled increase in remission rates, but one important study with another modulation of 5-FU with interferon alfa 2a (IFN-alpha-2a) had better results. In the fact that both modulations have different mechanisms of interaction, it seems hopeful that both have additive or synergistic effects and they give further increases of remission rates. Twenty-three patients with proven progressive advanced colorectal cancer were treated with 5-FU, FA, and IFN-alpha-2a in three different regimens. IFN-alpha-2a was given subcutaneously in a dose of 5 MioU per day during 5-FU treatment. In the first regimen FA (500 mg/m2) was administered in a short time infusion (30 minutes) while 5-FU (1,000 mg/m2) was given in a 24-hour continuous infusion with weekly intervals. In regimen 2 and 3 FA/5-FU treatment was given on days 1 to 5 every 3 to 4 weeks. The difference was time and dose of the 5-FU infusion (600 mg/m2 in 4-hour versus 350 mg/m2 by push injection). Three patients with isolated liver metastases and one patient with local recurrence of rectal carcinoma received regional therapy with higher 5-FU doses. Dose escalation was carried out in all regimens when possible (toxicity less than or equal to World Health Organization [WHO] grade 1). Objective response rates were reached in nine of 23 patients with two complete remissions (one in regional and systemic treatment) with a mean duration of 6 months. Eight patients had stable disease and six had therapy failure. In pretreated patients no complete remission was reached; three of seven had partial remission, two no change, and two progressive disease. Severe toxicity occurred in 12 of 23 patients with mucositis WHO grade 4 in one patient, grade 3 in two, hematotoxicity grade 3 in three, and cutaneous toxicity in two. Eight of twenty-three patients had alopecia grades 2 and 3. These early results of our phase II study with limited patients shows no significant advantage of double modulation in comparison to the well established results of FA/5-FU therapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intra-Arterial; Injections, Subcutaneous; Interferon alpha-2; Interferon-alpha; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Recombinant Proteins; Rectal Neoplasms

We compared the combined radiation therapy (RT) plus chemotherapy segments of two separate parallel phase I trials to determine if combined pelvic RT, fluorouracil (5-FU), and high-dose leucovorin (LV) had less acute toxicity when delivered preoperatively versus postoperatively in patients with rectal cancer.. Patients with unresectable disease received preoperative RT plus LV and 5-FU followed by surgery and postoperative LV and 5-FU. Patients with resectable disease received identical doses, techniques, and schedules of RT and LV and 5-FU except all therapy was delivered postoperatively. On day 1, patients received LV and 5-FU times one cycle. RT began on day 8. A second cycle of LV and 5-FU was given concurrently with the fourth week of RT.. Although more patients (75% v 32%; P = .02) received the higher dose level of 5-FU (250 mg/m2), significantly fewer experienced acute grade 3 to 4 toxicity with preoperative versus postoperative therapy (13% v 48%; P = .045). There was no grade 3 to 4 myelosuppression in either group. The two grade 3 toxicities in the preoperative group were gastrointestinal. The grade 3 toxicities in the postoperative group included seven gastrointestinal and two genitourinary; four patients had a grade 4 toxicity.. Given the high incidence of grade 3 to 4 toxicity also reported in the postoperative combined modality adjuvant randomized trials, future adjuvant trials should explore the preoperative approach.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Drug Administration Schedule; Drug Evaluation; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Radiotherapy; Radiotherapy Dosage; Rectal Neoplasms

Following surgery for Stages T3-4N0-2M0 primary and recurrent resectable rectal cancer limited to the pelvis, 25 patients have been entered on a Phase I trial of pelvic radiation therapy (RT) [5040 cGy] and 12 cycles of postoperative 5-FU and high dose Leucovorin (LV) chemotherapy. 5-FU was escalated 50 mg/m2 while the LV remained constant at 200 mg/m2. The initial doses of 5-FU were: combined-RT/chemotherapy = 200 mg/m2 and post-RT chemotherapy = 325 mg/m2. The median F/U was 25 months (range: 13-36). Two maximum tolerated doses (MTD's) have been determined, one for combined-RT/chemotherapy and one for post-RT chemotherapy. The MTD for combined-RT/chemotherapy was 250 mg/m2; therefore, the recommended dose of 5-FU is 200 mg/m2. The MTD for post-RT chemotherapy was 375 mg/m2; therefore, the recommended dose of 5-FU is 325 mg/m2. The dose limiting toxicities were diarrhea, tenesmus, frequent bowel movements, dysuria, and myelosuppression. For the nine patients who received 5-FU at the recommended dose level the median low counts were WBC 3.5 (2.2-4.0), HGB 10.3 (9.0-12.3), and PLT (x 1000) 167 (133-280), and the incidence of any grade greater than or equal to 3 toxicity was 22% diarrhea, 17% tenesmus, and 22% frequent bowel movements. The recommended dose of combined-RT/chemotherapy as used in this protocol was relatively well tolerated. However, optimal doses of 5-FU cannot be delivered until the fourth postoperative month. Therefore, despite the encouraging results reported with high dose LV in patients with advanced disease, we do not recommend that high dose LV be used with combined RT and 5-FU in the treatment regimen as presently designed.

Topics: Adenocarcinoma; Combined Modality Therapy; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Neoplasm Staging; Postoperative Care; Radiotherapy; Radiotherapy Dosage; Rectal Neoplasms

Recent clinical trials have suggested that a combination of folinic acid and 5-fluorouracil (5-FU) may improve response rates and survival in patients with advanced colorectal cancer. However, this regimen has been complicated by potentially life threatening toxicity. Regional delivery of folinic acid via a hepatic artery catheter might be expected to reduce systemic exposure and subsequent adverse effects. The present study compared the pharmacokinetic profiles of intravenous and intra-hepatic arterial infusions of folinic acid in patients with colorectal liver metastases (n = 6) who were being treated with weekly regional infusions of 5-FU. The mean area under the plasma concentration--time curve, the peak plasma concentration and the steady state volume of distribution were 163 micrograms ml-1 h-1 (SD 41), 18.5 micrograms ml-1 (SD 1.2) and 7.41 m-2 (SD 0.44) respectively following intravenous administration of folinic acid compared with 142 micrograms ml-1 h-1 (SD 45), 14.8 micrograms ml-1 (SD 2.4) and 11.21 m-2 (SD 1.22) following intra-hepatic arterial administration (P less than 0.05). Regional folinic acid was therefore associated with a statistically significant reduction in systemic exposure compared with the intravenous route.

Topics: Adenocarcinoma; Colonic Neoplasms; Fluorouracil; Humans; Infusions, Intra-Arterial; Infusions, Intravenous; Leucovorin; Metabolic Clearance Rate; Rectal Neoplasms

Seventy-nine patients with advanced, measurable, metastatic colorectal cancer previously unexposed to chemotherapy were randomly assigned to treatment with either fluorouracil (FUra) administered intravenously at a dose of 370 mg/m2/d for 5 days or the combination of FUra in the same dose and schedule with high-dose continuous infusion leucovorin calcium (500 mg/m2/d) beginning 24 hours before the first dose of FUra and continuing for 12 hours after the completion of FUra therapy. Patients whose disease progressed on treatment with FUra alone were, if eligible, crossed over to receive leucovorin and FUra. Three patients on the FUra plus leucovorin arm of the study were excluded from the analysis because they did not meet eligibility requirements. The treatment arms were well balanced for prognostic criteria including performance status, age, prior radiotherapy, distribution of metastatic sites, and on-study carcinoembryonic antigen (CEA), lactic dehydrogenase, and serum albumin. FUra plus leucovorin was superior to FUra alone for response (P = .0019) and for time to progression or death (log-rank, P = .045). Response rates were 16 of 36 (44%) versus five of 40 (13%), and median time to progression or death was 164 versus 120 days in the two arms of the trial, respectively. Overall survival, however, while longer in the FUra and leucovorin arm was not significantly so. An analysis of the toxicities experienced by the patients in the two treatment groups showed that, except for significantly more stomatitis in the leucovorin arm of the study, the side effects experienced by patients treated with either regimen were comparable. These results suggest that the efficacy of FUra in patients with advanced, measurable, metastatic colorectal cancer can be enhanced significantly by administration of a continuous high-dose infusion of leucovorin calcium.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Colonic Neoplasms; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Prospective Studies; Randomized Controlled Trials as Topic; Rectal Neoplasms; Survival Analysis

Topics: Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Colonic Neoplasms; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Male; Random Allocation; Rectal Neoplasms

We determined the therapeutic effect of fluorouracil (5-FU) in combination with folinic acid (FA) in patients with measurable recurrent or metastatic carcinoma of the colon or rectum by comparing it to standard 5-FU therapy in a prospective randomized controlled trial. Patients were randomized to receive either FA, 200 mg/m2/d for five consecutive days, or nothing. All patients received 5-FU, 370 mg/m2/d for five days on the first course, with subsequent dose modifications to maintain equal toxicity in the two arms. One hundred thirty patients were entered on trial and only five were excluded from the analysis because they did not meet the eligibility criteria or they refused therapy after randomization. The two treatment arms were balanced for 11 clinical characteristics. Patients were evaluated for response at the end of every two treatment courses and toxicity after every course of therapy. Median follow-up was 1.45 years. Dose-limiting toxicity was mucositis and diarrhea on this treatment schedule, although neutropenia was apparent. The response rate was 33% (21 of 63 patients) in the 5-FU and FA arm and was 7% (four of 61 patients) in the 5-FU arm (P less than .0005). Time to disease progression was significantly different in the combination arm as compared with the single-agent arm (P = .023). Overall survival was significantly longer for patients treated with 5-FU and FA as compared with those receiving 5-FU alone (P = .05). The median survival was 12.6 months for patients receiving the combination, and 9.6 months for those receiving 5-FU alone. Our results indicate that the combination of 5-FU and FA is effective treatment for patients with metastatic or recurrent carcinoma of the rectum and colon who have not received prior chemotherapy.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Colonic Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Random Allocation; Rectal Neoplasms

Topics: Adenocarcinoma; Adult; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Colonic Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Rectal Neoplasms

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Clinical Trials as Topic; Colonic Neoplasms; Drug Synergism; Fluorouracil; Humans; Infusions, Intra-Arterial; Infusions, Intravenous; Leucovorin; Methotrexate; Neoplasm Metastasis; Rectal Neoplasms

Seventy-four previously untreated patients with metastatic colorectal adenocarcinoma were prospectively randomized into one of three treatment regimens: (1) 5-fluorouracil (5-FU) 450 mg/m2 as an intravenous (IV) bolus daily for five days or toxicity, then 200 mg/m2 IV bolus every other day for six doses; (2) methotrexate (MTX) 50 mg/m2 in normal saline by IV infusion over four hours followed by an IV bolus of 5-FU 600 mg/m2. This was administered weekly for 4 weeks and then every 2 weeks. (3) Leucovorin 500 mg/m2 in a two-hour IV infusion of normal saline with 5-FU 600 mg/m2 as an IV bolus one hour after the Leucovorin began every week for 6 weeks. The combined complete and partial response rates in the three regimens were 11%, 5%, and 48%, respectively (P = .0009). The median duration of response in the 5-FU and Leucovorin regimen was 10 months. There was no statistically significant difference between the treatment regimens with respect to survival time (P = .6). Toxicity in the 5-FU and Leucovorin regimen was predominantly diarrhea (13 of 30 patients, 40%). In this regimen, eight of 13 patients (52%) who developed diarrhea not only required a dose reduction of 5-FU, but also hospitalization for IV hydration. The predominant toxicity in the 5-FU alone regimen and the 5-FU and MTX regimen was leukopenia. One drug-related death occurred in each regimen.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Colonic Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Palliative Care; Prospective Studies; Random Allocation; Rectal Neoplasms

The current study was initiated to confirm preliminary reports that 20% or more of patients with colorectal cancer who fail treatment with 5-fluorouracil (FUra) will respond to treatment with either leucovorin plus FUra or with sequential methotrexate, FUra, leucovorin. One hundred two patients with advanced, measureable colorectal cancer who failed treatment with FUra and/or 5-fluorodeoxyuridine (FUdR) were randomized to treatment with either high-dose leucovorin plus FUra (Arm B) or sequential methotrexate, FUra, leucovorin (Arm C). In this interim report, 92 patients were evaluable for toxicity and 89 patients were evaluable for response. Grade 3 or 4 nonhematologic toxicity which was primarily gastrointestinal was experienced by 25% of patients on both treatment arms during at least 1 treatment cycle. Hematologic toxicity was minimal. Among 43 evaluable patients on Arm B, there were 2 complete responses (5%) and 1 minor response (3%). Among 46 evaluable patients on Arm C, there was 1 complete response (2%), 1 partial response (2%), and 6 minor responses (14%). The median time to treatment failure was 2.2 months on Arm B and 3.5 months on Arm C. The median survival was 8.3 months on Arm B and 8.7 months on Arm C. Colorectal cancers that are resistant to FUra are cross-resistant to both experimental combinations.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Colonic Neoplasms; Drug Administration Schedule; Drug Resistance; Floxuridine; Fluorouracil; Humans; Leucovorin; Methotrexate; Rectal Neoplasms

Topics: Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Colonic Neoplasms; Fluorouracil; Forecasting; Humans; Leucovorin; Rectal Neoplasms

In this study, 50 patients were randomly assigned to treatment with 5-fluorouracil (FUra) or FUra plus high-dose continuous-infusion folinic acid. Five of 27 evaluable patients in the FUra group versus 10 of 21 patients in the FUra plus folinic acid arm of the study had objective partial remissions, P = 0.02. Time to progression was 3.9 months for FUra and 8.0 months for FUra and folinic acid, P = 0.006; however, median survivals (11.9 versus 14.5 months) were not different in this crossover study. Toxicity in both treatment arms was mild, although patients receiving FUra plus folinic acid experienced significantly more stomatitis than patients treated with FUra alone. This study suggests that high-dose, continuous-infusion folinic acid, which produces a steady-state level of biologically active folates of 10 microM, significantly increases the therapeutic activity of FUra.

Topics: Adenocarcinoma; Biological Availability; Colonic Neoplasms; Fluorouracil; Hematopoiesis; Humans; Infusions, Intravenous; Leucovorin; Rectal Neoplasms; Tetrahydrofolates

The North Central Cancer Treatment Group (NCCTG) and Mayo Clinic are collaborating in an ongoing, prospective, randomized clinical trial of new approaches to the chemotherapy of advanced metastatic colorectal cancer. Single agent 5-fluorouracil (FUra) given by intensive-course rapid intravenous administration serves as a control. Included among the experimental treatments are two regimens consisting of FUra plus leucovorin (folinic acid). One of these regimens uses folinic acid at a dose level of 200 mg/m2 daily for 5 days based on earlier studies by Machover et al. (4). The second regimen uses folinic acid at 1/10 the dose level (20 mg/m2 daily for 5 days), since this lower dose of folinic acid has been shown to produce peak serum levels equivalent to the concentration of folinic acid required in culture medium to produce optimal inhibition of L1210 cells by FUra in vitro, and because of the great expense of folinic acid when given at the higher dose levels. As of January 1986, 78 patients had been randomized to receive treatment with FUra alone or one of the FUra-folinic acid regimens. The toxicity of the folinic acid regimens has been clinically tolerable, with stomatitis and, to a lesser extent, diarrhea being dose-limiting. Hematologic toxicity has been very mild. There is suggestive evidence that folinic acid given at the higher dose level in combination with FUra at a constant dose produces more severe effects on the oropharyngeal mucosa. Preliminary tumor response and survival data remain blinded in accordance with NCCTG policy. Further patient accrual and follow-up are required to assess the therapeutic effect of these folinic acid regimens compared to FUra given alone.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Cisplatin; Colonic Neoplasms; Dose-Response Relationship, Drug; Fluorouracil; Hematopoiesis; Humans; Leucovorin; Methotrexate; Prospective Studies; Rectal Neoplasms

In order to determine the clinical applicability of the in vitro observation of enhanced cytotoxicity of 5-fluorouracil (5-FU) in the presence of excess reduced folates, the Southwest Oncology Group (SWOG) performed a randomized trial evaluating two dose schedules of 5-FU and folinic acid (FA) in 128 patients with metastatic colorectal cancer. Of 125 eligible patients, 62 were randomized to receive bolus FA (200 mg/m2 days 1 through 4) in addition to 5-FU (1,000 mg/m2 days 1 through 4) by continuous four-day infusion (infusion arm), while 63 were randomized to receive bolus FA (200 mg/m2 days 1 through 5) in addition to 5-FU (325 mg/m2 days 1 through 5) by bolus injection (bolus arm). The toxicities of the two schedules differed, with stomatitis being more severe in the infusion arm and leukopenia being more severe in the bolus arm. The response rates and survival data for the two arms are nearly identical. The median survival of patients on the infusion arm is 11.0 months and of patients on the bolus arm, 10.3 months. The infusion arm produced one complete response (CR) and 12 partial responses (PRs), for a major response rate of 21% of eligible patients. The bolus arm produced three CRs and 11 PRs, for a major response rate of 22% of eligible patients. The response rate produced is minimally superior to recent cooperative group studies of colorectal cancer, but the response rate and survival experience are within the range of experience for treatment with 5-FU alone.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Colonic Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Random Allocation; Rectal Neoplasms

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Clinical Trials as Topic; Colonic Neoplasms; Doxorubicin; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Methotrexate; Rectal Neoplasms; Semustine; Vincristine

We report the results of an expanded trial of 5-fluorouracil (5-FU) combined with high-dose folinic acid for treatment of patients with advanced colorectal or advanced gastric adenocarcinoma. In each treatment course, the patients received both 5-FU (340 to 400 mg/m2/d by intravenous (IV) infusion for a period of 15 minutes) and folinic acid (200 mg/m2/d by IV bolus) for 5 consecutive days, with a 21-day interval between courses. Eighty-six patients with colorectal carcinoma were evaluated. The combined complete and partial response rates were 39% for 54 patients who did not receive prior chemotherapy and 22% for 32 patients who had previously received chemotherapy. Four patients who were previously resistant to 5-FU attained objective responses. The median time to disease progression for the 28 responders was 10 months. The median survival time of responders was 19.5 months, and the probability of their being alive at 2 years was 40%. Of 27 patients with gastric adenocarcinoma, 13 (48%) responded to therapy. Their median time to disease progression was 5.5 months. The median survival time of responders was 11 months, and their probability of being alive at 15 months was 30%. Toxicity was within acceptable limits. Toxic effects included stomatitis, diarrhea, conjunctivitis, skin rash, and mild myeloid hypoplasia. In a separate study, plasma concentrations of L-folates greater than 10(-5) mol/L were achieved after a rapid single IV injection of 200 mg/m2 of folinic acid. Comparisons of our results with those reported in previous studies on 5-FU administered as a single agent suggest that, in advanced colorectal and gastric adenocarcinoma, folinic acid administered in high doses enhances the effectiveness of 5-FU administered concomitantly. Furthermore, some colorectal tumors that were previously resistant to 5-FU become sensitive to this drug. The survival of the patients who responded to therapy was markedly improved over that observed in reported series of untreated patients with advanced colorectal and gastric adenocarcinomas.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Colonic Neoplasms; Female; Fluorouracil; Humans; Kinetics; Leucovorin; Male; Middle Aged; Rectal Neoplasms; Stomach Neoplasms; Time Factors

Forty-five patients with metastatic colorectal carcinoma were treated with low-dose methotrexate (MTX) and 5-fluorouracil (5-FU) given sequentially. The dose of MTX was 40 mg/m2 intravenously (IV) on days 1 and 8 followed 24 hours later by 5-FU at 600 mg/m2 IV on days 2 and 9; the drugs were recycled every 28 days. Fourteen (32%) of 43 adequately treated patients had a complete or partial response lasting a median of nine months (range, 6-15 + months). Four patients had a minor response and seven patients had stable disease for a median of nine and 10 months, respectively. Toxicity included mucositis in 28 (65%) patients, diarrhea in 18 (40%), nausea in 11 (24%), and vomiting in seven (16%). Hematologic toxicity was mild: six patients had nadir white blood cell counts less than 3.5 X 10(3) cells/microL, and seven patients had a nadir platelet count less than 100 X 10(3) cells/microL. Serial biopsies and blood samples were obtained in selected patients to evaluate the effect of MTX on tissue and lymphocyte phosphoribosylpyrophosphate (PRPP) and PRPP synthetase levels.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Colonic Neoplasms; Diarrhea; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Lymphocytes; Male; Methotrexate; Middle Aged; Mucous Membrane; Nausea; Pentosephosphates; Phosphoribosyl Pyrophosphate; Phosphotransferases; Prospective Studies; Rectal Neoplasms; Ribose-Phosphate Pyrophosphokinase; Thrombocytopenia; Vomiting

Thirty patients with advanced measurable colorectal cancer were randomized to receive either methotrexate (MTX) 200 mg/m2 or 40 mg/m2, followed in four hours by 5-fluorouracil (5-FU) 600 mg/m2. Patients receiving the higher dose MTX were given leucovorin rescue 24 hours later. Eight of 13 patients treated with 200 mg/m2 MTX + 5-FU developed severe hematologic toxicity, leading to two toxic deaths. In addition, 9/13 developed mild azotemia, and three patients had severe gastrointestinal toxicity. No patients with prior chemotherapy responded to either regimen. Among those without prior chemotherapy, there were two of six and three of eight partial responses, respectively, in the 200 mg/m2 and 40 mg/m2 MTX regimens. Sequential 200 mg/m2 MTX followed by 5-FU after four hours has unacceptable toxicity. Sequential treatment with standard dose MTX + 5-FU is tolerable and merits further study.

Topics: Aged; Clinical Trials as Topic; Colonic Neoplasms; Digestive System; Drug Therapy, Combination; Fluorouracil; Humans; Leucovorin; Leukopenia; Liver Neoplasms; Lung Neoplasms; Methotrexate; Middle Aged; Rectal Neoplasms; Uremia

To evaluate the safety and effectiveness of aflibercept in combination with fluorouracil, leucovorin, and irinotecan (FOLFIRI) in Korean patients with metastatic colorectal cancer (mCRC) who progressed with oxaliplatin-containing regimen.. This was a prospective observational study conducted at 22 sites across Korea between February 2018 and September 2019. Patients aged > 19 years with a diagnosis of mCRC who were prescribed aflibercept plus FOLFIRI, after progression with an oxaliplatin-containing regimen were included. Disease assessment was performed every 6 weeks.. A total of 185 patients were included (males, 58.9%; right-sided tumors, 23.8%; and ECOG performance factor ≥ 1, 68.6%). A total of 514 adverse events (AEs) occurred in 134 patients, of which 206 (49.2%; 95% CI 42.0%, 56.4%) events were considered as adverse drug reactions (ADRs), 172 unexpected AEs (49.7%; 95% CI 42.5%, 56.9%), and 53 serious AEs (22.2%; 95% CI16.2%, 28.2%). The most common serious ADR was pneumonia (n = 2, 1.6%). The most common all grade hematological AE and non-hematological AE were neutropenia (21.6%) and nausea (16.2%), respectively. Over a median follow-up of 5.6 months, a total of five grade 5 (1.0%) AEs were reported. Median OS was 9.4 months, and median progression-free survival (PFS) was 7.3 months. The overall response rate was 14.6%. Right-sided tumor location and prior bevacizumab treatment were independent factors of poor PFS in multivariate analysis.. Aflibercept in combination with FOLFIRI was effective and showed an acceptable safety profile in Korean patients with mCRC in daily clinical practice.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Male; Oxaliplatin; Rectal Neoplasms; Republic of Korea

Safety and effectiveness of aflibercept with 5-fluorouracil/levofolinate/irinotecan have not been reported in Japanese patients with metastatic colorectal cancer (mCRC) in a real-world clinical setting.. This post-marketing surveillance enrolled patients with un-resectable advanced or recurrent mCRC who were prescribed aflibercept from December 2017 to June 2019 in Japan. Data, collected up to 1 year from starting treatment, included patient background, safety, and effectiveness assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or physician's evaluation.. Of 261 patients registered from 64 centers, 235 [53.2% male with a median age of 67 years (range 28-84)] received treatment and were included in the safety analysis. Aflibercept was received at 1st, 2nd, and ≥ 3rd line in 1.3%, 48.1%, and 50.2% of patients, respectively. Median number of treatment cycles was 6 (range 1-22) and relative dose intensity was 75.4% (range 14.3-101.8%). Adverse events (all grades) were reported in 88.5% of patients, including neutropenia (34.5%), proteinuria (24.7%), hypertension (17.0%), diarrhea (17.0%), and decreased appetite (15.3%). Three treatment-related deaths occurred by perforation of the digestive tract, pneumonia and gastrointestinal bleeding, and sudden death. The effectiveness analysis included 198 patients. Overall response rate was 6.1% (1st line, 0%; 2nd line, 10.1%; ≥ 3rd line, 2.1%) and disease control rate was 47.5% (1st line, 100%; 2nd line, 58.6%; ≥ 3rd line, 34.4%).. No new risks of aflibercept were identified in real clinical practice. Effectiveness in patients at the 2nd line was consistent with previous reports.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Colorectal Neoplasms; East Asian People; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Product Surveillance, Postmarketing; Receptors, Vascular Endothelial Growth Factor; Rectal Neoplasms

Irinotecan is a useful anticancer drug for colorectal cancer treatment. UGT1A1*28 and *6 gene polymorphisms are known risk factors for irinotecan-associated toxicity. However, severe adverse effects due to irinotecan have been observed even in patients who do not harbor UGT1A1*28 or *6. We investigated gene polymorphisms in the whole exome to identify useful biomarkers for irinotecan toxicity other than UGT1A.. A total of 178 patients with metastatic colorectal cancer (mCRC) and 87 patients with pancreatic cancer were treated with FOLFIRI, FOLFOX, FOLFOXIRI, modified FOLFIRINOX, or gemcitabine plus nab-paclitaxel. Genome-wide screening was performed using whole-exome sequencing (WES), and validation analysis was performed using qPCR with a hydrolysis probe.. Using WES after a doublet chemotherapy regimen comprising irinotecan and 5-fluorouracil (n = 15), seven single nucleotide polymorphisms (SNPs) were identified as candidate biomarkers for irinotecan-associated toxicity of neutropenia. Among the seven SNPs, an SNP in R3H domain and coiled-coil containing 1 (R3HCC1; c.919G > A, rs2272761) showed a significant association with neutropenia (>grade 3) after doublet chemotherapy. Patients receiving irinotecan including triplet chemotherapy, FOLFOXIRI for mCRC (n = 23) or modified FOLFIRINOX for pancreatic cancer (n = 40), also showed significant linear trends between R3HCC1 polymorphism and neutropenia (p = 0.017 and 0.046, respectively). No significant association was observed in patients treated with irinotecan-free regimens, FOLFOX for mCRC (n = 66), and gemcitabine plus nab-paclitaxel for pancreatic cancer (n = 47).. Thus, an SNP in the R3HCC1 gene may be a useful biomarker for the toxicity of irinotecan-containing chemotherapy for mCRC and pancreatic cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Humans; Irinotecan; Leucovorin; Neutropenia; Pancreatic Neoplasms; Polymorphism, Single Nucleotide; Rectal Neoplasms

Topics: Administration, Oral; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Humans; Leucovorin; Mitomycin; Rectal Neoplasms; Tegafur; Uracil

The benefit of adding the antiangiogenic drug aflibercept to FOLFIRI regime in metastatic colorectal cancer (CRC) patients resistant to or progressive on an oxaliplatin-based therapy has been previously demonstrated. However, the absence of validated biomarkers to predict greater outcomes is a major challenge encountered when using antiangiogenic therapies. In this study we investigated profiles of circulating microRNAs (miRNAs) to build predictive models of response to treatment and survival. Plasma was obtained from 98 metastatic CRC patients enrolled in a clinical phase II trial before receiving FOLFIRI plus aflibercept treatment, and the circulating levels of 754 individual miRNAs were quantified using real-time PCR. A distinct signature of circulating miRNAs differentiated responder from non-responder patients. Remarkably, most of these miRNAs were found to target genes that are involved in angiogenic processes. Accordingly, some of these miRNAs had predictive value and entered in predictive models of response to therapy, progression of disease, and survival of patients treated with FOLFIRI plus aflibercept. Among these miRNAs, circulating levels of hsa-miR-33b-5p efficiently discriminated between responder and non-responder patients and predicted the risk of disease progression. Moreover, the combination of circulating VEGF-A and miR-33b-5p levels improved clinical stratification of metastatic CRC patients who were to receive FOLFIRI plus aflibercept treatment. In conclusion, our study supports circulating miRNAs as valuable biomarkers for predicting better outcomes in metastatic CRC patients treated with FOLFIRI plus aflibercept.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Circulating MicroRNA; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; MicroRNAs; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Rectal Neoplasms

The second-line chemotherapy in metastatic colorectal cancer (mCRC) with FOLFIRI-aflibercept demonstrated an increase in survival compared with FOLFIRI in patients previously treated with oxaliplatin-based regimens. Few data are available in patients treated previously with bevacizumab. Our objective is to evaluate the efficacy and safety of FOLFIRI-aflibercept in second-line treatment in patients who have previously received bevacizumab.. This is a observational, retrospective study of patients with mCRC treated with FOLFIRI-aflibercept in 2nd line in eight hospitals in the Valencian Community. Survival, response, and toxicity were analyzed.. 122 patients with a median age of 61 years were included. 89% of patients had PS 0-1. The median of PFS (progression free survival) and OS (overall survival) was 5.45 (95% CI 4.74-6.15 months) and 10.15 (95% CI 7.47-12.82 months), respectively. Disease control rate 59.8%. The most common grade 3-4 adverse events were neutropenia (13,1%) and asthenia (9%). The presence of hypertension during treatment with FOLFIRI-aflibercept was associated with a survival benefit. Median of OS was 14.45 (95% CI 11.58-17.32) in patients with hypertension vs 7.78 (95% CI 5.02-10.54) in patients without hypertension (p = .001). Our results suggest that the presence of PS 0, primary tumor surgery, metachronous metastases, and the presence of only 1 metastatic location, are favorable prognostic factors associated with better OS.. Our results confirm the value of maintaining angiogenesis inhibition with FOLFIRI-aflibercept in mCRC after progression to a first-line treatment with bevacizumab. The development of hypertension during treatment is a possible predictive marker of response.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Humans; Hypertension; Leucovorin; Middle Aged; Neoplasm Metastasis; Recombinant Fusion Proteins; Rectal Neoplasms; Retrospective Studies

The patient was 40s male, who underwent laparoscopic low anterior resection for his upper rectal cancer with final pathology results of tub2, pT3(SS), no lymph metastasis and fStage Ⅱ. He was followed up without adjuvant chemotherapy. Half a year after surgery, tumor marker was elevated and CT scan revealed multiple liver metastases. He was treated with oxaliplatin, irinotecan, Leucovorin and 5-fluorouracil(FOLFOXIRI)plus bevacizumab because of RAS mutant type. In the third courses, he has pain in the lower extremities and was diagnosed with acute lower extremity arterial occlusion. Subsequently, chemotherapy was resumed with the exception of bevacizumab, in combination with DOAC, which resulted in tumor shrinkage and allowed resection of the liver metastases.

Topics: Acute Disease; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Neoplasm Recurrence, Local; Rectal Neoplasms

We analyzed the effectiveness, safety, and mid-term oncological outcomes of short-course radiotherapy (SCRT) and oxaliplatin-based consolidation chemotherapy in patients with locally advanced rectal cancer (LARC).. We retrospectively evaluated 64 patients with LARC who underwent SCRT and tegafox (tegafur-uracil/leucovorin plus oxaliplatin) or mFOLFOX-6 (5-fluorouracil, leucovorin, and oxaliplatin) consolidation chemotherapy before surgery between January 2015 and December 2020. Tumor response, patient compliance, toxicity, surgical outcomes, overall survival (OS), and disease-free survival (DFS) were analyzed.. Sixty-four patients with a mean age of 58.67 years (44 males) were included; 48 (75%) had tumors within 5 cm of the anal verge. Additionally, 93.8% of the patients underwent at least 2 months of chemotherapy, and three required dose reduction. Grade III toxicity occurred in 2 patients, and 10 had a clinical complete response and opted for non-operative management. One patient experienced tumor progression and underwent further treatment without surgery. Among the 53 patients who underwent surgery, 51 (96.2%) had sphincter preservation, 3 had Clavien-Dindo grade III complications, and no mortality occurred. The complete response rate for the entire cohort was 23.4%. Moreover, 47 patients (74.6%) had a neoadjuvant rectal score of < 16 after treatment. After a median follow-up time of 32.01 months, 6 (9.3%) had local recurrence, and 17 (26.6%) had distant metastasis. The 3-year OS, DFS and stoma-free rates were 89.5%, 65.5%, and 78.1% respectively.. SCRT followed by oxaliplatin-based consolidation chemotherapy is safe and effective for tumor downstaging in LARC, further improving the sphincter preservation rate.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Consolidation Chemotherapy; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organ Preservation; Oxaliplatin; Rectal Neoplasms; Retrospective Studies; Treatment Outcome

Fluoropyrimidine (FP) with oxaliplatin-based chemotherapy is the standard first-line treatment for metastatic colorectal cancer (mCRC); however, oxaliplatin-induced neuropathy critically affects the quality of life of patients. Maintenance strategies with FP plus bevacizumab have been well-established; nonetheless, the real-world outcomes of maintenance therapy with FP and cetuximab are unclear. We investigated the clinical outcomes of patients who underwent maintenance therapy with cetuximab.. We retrospectively identified and analyzed patients with mCRC who were treated between 2012 and 2021 with first-line oxaliplatin-based induction chemotherapy (IC) plus biologic agents (either cetuximab or bevacizumab), and underwent maintenance therapy (IC regimen without oxaliplatin) after IC.. In total, 19 patients who were treated with mFOLFOX6 (FP/leucovorin/oxaliplatin) with cetuximab, and 26 patients who were treated with mFOLFOX6 with bevacizumab were included. In the cetuximab group, all patients were KRAS-, NRAS-, and BRAF-wild type, whereas most patients in the bevacizumab group harbored KRAS or BRAF. Maintenance therapy with FP plus biologic agents (either bevacizumab or cetuximab) is a feasible strategy for appropriate mCRC patients according to their RAS/BRAF status. Further large-scale randomized studies are needed to validate the efficacy of anti-epidermal growth factor receptor-based maintenance therapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Biological Factors; Cetuximab; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Mutation; Oxaliplatin; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras); Quality of Life; Rectal Neoplasms; Retrospective Studies

Fluoropyrimidine therapy or oxaliplatin combination therapy is recommended for patients with stage III colorectal cancer as adjuvant chemotherapy (AC). However, the criterion for selecting these regimens is still unclear in patients with stage III rectal cancer (RC). In order to select an appropriate regimen of AC for such patients, it is needed to identify characteristics associated with tumor recurrence.. The records of 45 patients with stage III RC undergoing AC using tegafur-uracil/leucovorin (UFT/LV) were retrospectively reviewed. The cut-off value of characteristics was determined using a receiver operating characteristic curve for recurrence. Univariate analyses using Cox-Hazard model for predicting recurrence were performed with clinical characteristics. Survival analysis was performed using Kaplan-Meier method and log-rank test.. Thirty patients (66.7%) completed AC using UFT/LV. Fifteen patients (33.3%) did not complete AC because of adverse events, tumor recurrence and others. Sixteen patients (35.6%) had recurrence. Univariate analyses revealed that lymph node metastasis (N2/N1) (p=0.002) was associated with tumor recurrence. Survival analysis showed that lymph node metastasis (N2/N1) could stratify recurrence-free survival (p<0.001).. N2 lymph node metastasis can predict tumor recurrence in patients with stage III RC undergoing AC using UFT/LV.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colorectal Neoplasms; Humans; Leucovorin; Lymphatic Metastasis; Neoplasm Recurrence, Local; Neoplasm Staging; Rectal Neoplasms; Retrospective Studies; Tegafur; Uracil

The association between prior bevacizumab (BEV) therapy and ramucirumab (RAM)-induced proteinuria is not known. We aimed to investigate this association in patients with metastatic colorectal cancer (mCRC).. mCRC patients who received folinic acid, fluorouracil, and irinotecan (FOLFIRI) plus RAM were divided into with and without prior BEV treatment groups. The cumulative incidence of grade 2-3 proteinuria and rate of RAM discontinuation within 6 months (6M) after RAM initiation were compared between the two groups.. We evaluated 245 patients. In the Fine-Gray subdistribution hazard model including prior BEV, age, sex, comorbidities, eGFR, proteinuria ≥ 2 + at baseline, and later line of RAM, prior BEV treatment contributed to proteinuria onset (P < 0.01). A shorter interval between final BEV and initial RAM increased the proteinuria risk; the adjusted odds ratios (95% confidence intervals) for the intervals of < 28 days, 28-55 days, and > 55 days (referring to prior BEV absence) were 2.60 (1.23-5.51), 1.51 (1.01-2.27), and 1.04 (0.76-1.44), respectively. The rate of RAM discontinuation for ≤ 6M due to anti-VEGF toxicities was significantly higher in the prior BEV treatment group compared with that in the no prior BEV treatment group (18% vs. 6%, P = 0.02). Second-line RAM discontinuation for ≤ 6M without progression resulted in shorter overall survival of 132 patients with prior BEV treatment (P < 0.01).. Sequential FOLFIRI plus RAM after BEV failure, especially within 55 days, may exacerbate proteinuria. Its escalated anti-VEGF toxicity may negatively impact the overall survival.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Cohort Studies; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Humans; Incidence; Leucovorin; Proteinuria; Ramucirumab; Rectal Neoplasms

Rectal carcinomas are tumors that arise from the last 12 cm of the large intestine closest to the anus. They generally have a modest prognosis exacerbated by a high local recurrence rate if radiosensitizing chemotherapy is not given during radiotherapy. This case report discusses the clinical trial treatment of a patient with rectal adenocarcinoma by a new ropidoxuridine-capecitabine-radiotherapy combination. This case report is novel due to the patient's participation in an accelerated titration phase I clinical trial and the resultant rare adverse event of treatment-related sigmoid typhlitis.. The patient was an 82-year-old female who noticed hematochezia and change in stool caliber over a period of 3 months. A rectal mass was identified by biopsy as a microsatellite stable adenocarcinoma. A planned total neoadjuvant treatment involved eight cycles of leucovorin calcium (folinic acid)-fluorouracil-oxaliplatin (mFOLFOX6) chemotherapy, followed by a clinical trial combination of ropidoxuridine-capecitabine-radiotherapy, prior to definitive surgery. The patient began daily intensity modulated pelvic radiotherapy with concurrent twice-daily oral ropidoxuridine and twice-daily oral capecitabine to be given over 6 weeks. After 14 days of ropidoxuridine-capecitabine-radiotherapy, the patient developed sigmoid typhlitis requiring a 10-day hospitalization and 14-day disruption of treatment. The patient died 27 days after the start of ropidoxuridine-capecitabine-radiotherapy. This adverse event was listed as a definite attribution to the ropidoxuridine-capecitabine treatment; pharmacokinetic and pharmacodynamic data showed low ropidoxuridine metabolite DNA incorporation and high capecitabine metabolite concentration. The accelerated titration phase I clinical trial has been subsequently closed to accrual (NCT04406857).. We believe this case report demonstrates the decision-making process for terminating a phase I accelerated titration designed clinical trial. The report also presents the rare complication of sigmoid typhlitis as a treatment-attributed adverse event. In this case, a ropidoxuridine-capecitabine combination was used as an investigational radiosensitizing treatment now with a narrower future clinical development pathway.

Topics: Adenocarcinoma; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Female; Fluorouracil; Humans; Leucovorin; Neoadjuvant Therapy; Neoplasm Staging; Rectal Neoplasms; Typhlitis

Few studies have focused on the impact of single-organ pulmonary metastases on progression-free survival and overall survival in patients with metastatic colorectal cancer. Recognizing differences in prognosis and chemotherapeutic efficacy based on metastasized organs may help in optimizing treatment strategies. The exploratory study was conducted to evaluate the comparative clinical outcomes and prognoses of patients with metastatic colorectal cancer presenting with single-organ pulmonary metastases and treated with folinic acid, 5-fluorouracil, irinotecan, and vascular endothelial growth factor inhibitors as second-line chemotherapy.. This retrospective study included 289 patients with metastatic colorectal cancer treated with second-line folinic acid, 5-fluorouracil, irinotecan, and vascular endothelial growth factor inhibitors. The response rate, disease control rate, progression-free survival, and overall survival were assessed in the participants.. Among the 289 patients enrolled, 26 (9.0%) had single-organ pulmonary metastasis with left-sided primary locations, lower levels of tumor markers at the initiation point of chemotherapy, a significantly higher disease control rate (96.2% vs. 76.7%, P = .02), and a longer progression-free survival (median 29.6 months vs. 6.1 months, P < .001) and overall survival (median 41.1 months vs. 18.7 months, P < .001) than patients with other forms of metastatic colorectal cancer. Multivariate analysis showed that single-organ pulmonary metastasis was an independent predictor of longer progression-free survival (hazard ratio 0.35, P = .00075) and overall survival (hazard ratio 0.2, P = .006).. Single-organ pulmonary metastasis was a strong predictor of progression-free survival and overall survival in patients with metastatic colorectal cancer treated with folinic acid, 5-fluorouracil, irinotecan, and vascular endothelial growth factor inhibitors as second-line chemotherapy; this provides preliminary evidence for medical guidelines and clinical decision-making on novel therapeutic strategies for these patients.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Humans; Irinotecan; Leucovorin; Lung Neoplasms; Neoplasm Metastasis; Prognosis; Rectal Neoplasms; Retrospective Studies; Vascular Endothelial Growth Factor A

BRAF V600E mutant-metastatic colorectal cancer (mCRC) is characterized by its short survival time. Treatment approaches vary depending on whether or not the metastases are initially resectable. The benefit of metastasectomy remains unclear, and the optimal first-line treatment is controversial. This study aimed to describe the prognosis of BRAF V600E mutant-mCRC, analyze the recurrence pattern in resectable patients, and explore the optimal first-line treatment for unresectable patients.. Patients diagnosed with BRAF V600E mutant-mCRC between February 2014 and January 2022 in five hospitals were enrolled. Date on clinical and pathological characteristics, treatment features, and survival outcomes were collected.. Of the 220 included patients, 64 initially resectable patients had a significantly longer overall survival (OS) (37.07 vs. 20.20 months, P < 0.001) than initially unresectable patients. Of 156 unresectable patients, 54 received doublet (FOLFOX, XELOX or FOLFIRI) or triplet (FOLFOXIRI) chemotherapies (Chemo), 55 received Chemo plus Bevacizumab (Chemo+Bev), and 33 received vemurafenib plus cetuximab and irinotecan (VIC). The VIC regimen had a better progression-free survival (PFS) (12.70 months) than the Chemo (6.70 months, P < 0.001) and Chemo+Bev (8.8 months, P = 0.044) regimens. Patients treated with VIC had the best overall response rate (60.16%, P < 0.001), disease control rate (93.94%, P < 0.001) and conversional resection rate (24.24%, P = 0.003).. Metastasectomy is beneficial to the survival of patients with BRAF V600E mutant-mCRC. For initially unresectable patients, VIC as first-line therapy is associated with a better prognosis and efficacy than doublet and triplet chemotherapy with or without bevacizumab.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Cetuximab; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Humans; Irinotecan; Leucovorin; Mutation; Proto-Oncogene Proteins B-raf; Rectal Neoplasms; Vemurafenib

To assess the cost-effectiveness of cetuximab in combination with chemotherapy fluorouracil, oxaliplatin, and leucovorin (FOLFOX) or fluorouracil, irinotecan and leucovorin (FOLFIRI) compared to standard chemotherapy alone as a first-line treatment for metastatic colorectal cancer (mCRC) with positive KRAS wild type patients in Indonesia.. A cost-utility analysis applying Markov model was constructed, with a societal perspective. Clinical evidence was derived from published clinical trials. Direct medical costs were gathered from hospital billings. Meanwhile, direct non-medical costs, indirect costs, and utility data were collected by directly interviewing patients. We applied 3% discount rate for both costs and outcomes. Probabilistic sensitivity analysis was performed to explore the model's uncertainty. Additionally, using payer perspective, budget impact analysis was estimated to project the financial impact of treatment coverage.. There was no significant difference in life years gained (LYG) between cetuximab plus FOLFOX/FOLFIRI and chemotherapy alone. The incremental QALY was only one month, and the incremental cost-effectiveness ratio (ICER) was approximately IDR 3 billion/QALY for cetuximab plus chemotherapy. Using 1-3 GDP per capita (IDR 215 million or USD 14,350) as the current threshold, the cetuximab plus chemotherapy was not cost-effective. The budget impact analysis resulted that if cetuximab plus chemotherapy remain included in the benefits package under the Indonesian national health insurance (NHI) system, the payer would need more than IDR 1 trillion for five years.. The combination of cetuximab and chemotherapy for mCRC is unlikely cost-effective and has a substantial financial impact on the system.

Topics: Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cetuximab; Colonic Neoplasms; Colorectal Neoplasms; Cost-Benefit Analysis; Fluorouracil; Humans; Indonesia; Leucovorin; Oxaliplatin; Rectal Neoplasms

Colorectal cancer (CRC) mainly affects older patients. The pivotal VELOUR phase III trial of aflibercept plus FOLFIRI in metastatic CRC (mCRC) included only 5.9% of patients aged ≥75 years. Herein, we report a preplanned analysis from QoLiTrap, a large prospective observational study evaluating the impact of age on quality of life (QoL), effectiveness, and safety of aflibercept plus FOLFIRI in daily clinical practice in Europe.. Enrolled patients had progressive mCRC, had failed a prior oxaliplatin-based regimen, and had received aflibercept (4 mg/kg) plus FOLFIRI every two weeks until disease progression, death, unacceptable toxicity, or physician/patient decision. Analyses were performed by age classes (<60, 60-64, 65-69, 70-74, and ≥ 75 years). The primary endpoint was the percentage of patients whose global health status (GHS) of the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) was maintained (i.e., no worsening from baseline by at least 5% over a 12-week treatment). Secondary endpoints included tumor objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety.. Overall, 1277 patients (<60 years, n = 327; 60-64 years, n = 231; 65-69 years, n = 227; 70-74 years, n = 259; and ≥ 75 years, n = 233) were treated, of whom 872 were evaluable for QoL. GHS was maintained in 36.5%, 41.6%, 38.9%, 41.8%, and 44.8% of patients aged <60, 60-64, 65-69, 70-74, and ≥ 75 years, respectively. Age did not influence PFS (median 7.8 months), OS (median 14.4 months), or ORR (20.8%). Number of cycles, dose delays for any cause, and dose reductions for adverse events (AEs) were comparable between age classes. Grade ≥ 3 AEs occurred in 47.7%, 51.9%, 51.5%, 55.2%, and 55.8% of patients aged <60, 60-64, 65-69, 70-74, and ≥ 75 years, respectively. The main grade ≥ 3 AEs were hypertension (11.2%) and diarrhea (9%) in patients aged ≥75 years.. The results suggest that aflibercept plus FOLFIRI maintains QoL and retains its activity, including a high objective tumor response, regardless of age and treatment line. In fit older patients, the safety profile seems manageable, with no new safety signals.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Prospective Studies; Quality of Life; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Rectal Neoplasms

To assess the toxicity patterns and effectiveness of doublet chemotherapy when administered at reduced doses of 20% (FOLFOX or FOLFIRI) in combination with anti-EGFR antibodies (cetuximab or panitumumab) in old, vulnerable patients with metastatic colorectal cancer (mCRC).. We performed a retrospective observational study of RAS and BRAF wild-type, vulnerable patients aged ≥70 years with previously untreated mCRC. The primary endpoint was safety, and secondary endpoints were overall response rate (ORR), progression-free survival (PFS), and overall survival (OS).. One hundred and eighteen patients were collected from 14 selected Italian centres. The median age was 75 (range, 70-85). Geriatric screening by G8 tool gave a score ≤ 14 in all patients. In total, 75 and 43 patients received FOLFOX or FOLFIRI, respectively, in combination with panitumumab (53%) or cetuximab (47%). The overall incidence of grade (G) 3-4 neutropenia was 11.8%, and for skin rash 11%. The most frequent adverse events were G1-2 skin rash (49.1%), G1-2 diarrhea (21.1%) and G1-2 nausea (17.7%). The ORR was 57.3%. Stable disease was observed in 29.1% of patients, with a disease control rate of 86.4%. With a median follow-up of 18 months, the median PFS was 10.0 months (95% confidence interval [CI]: 8.5-11.4), while the median OS was 18.0 months (95% CI: 16.0-19.9). No statistically significant difference was observed between the regimens in terms of ORR, PFS (p = 0.908), and OS (p = 0.832).. This study shows that with an appropriate design, including reduced doses, vulnerable older patients best tolerate chemotherapy when combined with anti-EGFR antibodies.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cetuximab; Colonic Neoplasms; Colorectal Neoplasms; Exanthema; Fluorouracil; Humans; Leucovorin; Panitumumab; Rectal Neoplasms

Some patients with cancer may present with progressive or persistent disease at a limited number of sites following a period of treatment response. We evaluated the safety and effectiveness of metastasis-directed radiotherapy (MRT) for oligoprogressive or oligopersistent disease in patients receiving systemic treatment for metastatic colorectal cancer (mCRC).. Patients with mCRC who received 5-fluorouracil, leucovorin, and oxaliplatin; 5-fluorouracil, leucovorin, and irinotecan; and/or capecitabine chemotherapy between 2011 and 2020 at a single institution were identified. Then, those who underwent MRT for five or fewer lesion sites while receiving systemic treatment for other metastases were categorized. The primary endpoint was time to change to systemic therapy. Secondary endpoints included MRT-related toxicity, overall survival, and local control.. Among 4157 patients included, 91 (2%) received MRT to limited lesion sites (55 oligoprogressive and 36 oligopersistent) during systemic treatment following a period of treatment response. The median time to change to next-line systemic therapy was 5 months in the overall cohort (measured from the current chemotherapy session) and 9.5 (range, 6.0-40.6) months in the MRT group (measured from the MRT session). No severe toxicity or systemic treatment interruption was observed following MRT. The 1-year local control and overall survival rates were 69% and 99%, respectively.. In patients with oligoprogressive or oligopersistent mCRC, MRT may be performed safely in conjunction with systemic treatment to maximize the benefit of systemic therapy and to prolong the time to change to systemic therapy. Further prospective studies should confirm these findings.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Neoplasm Metastasis; Prospective Studies; Rectal Neoplasms

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Fluorouracil; Humans; Irinotecan; Leucovorin; Neoadjuvant Therapy; Oxaliplatin; Pancreatic Neoplasms; Rectal Neoplasms

In this follow-up of the R-NAC-01 study, we assessed the long-term oncological benefit of four courses of modified leucovorin, 5-fluorouracil (FU), and oxaliplatin (mFOLFOX6) chemotherapy before rectal surgery.. In this prospective, multicenter study (UMIN 000012559) involving 11 hospitals in Japan, patients with lower rectal cancer underwent four cycles of mFOLFOX6 chemotherapy and subsequent surgery within four to six weeks. The 3-year recurrence-free survival and local recurrence rates were then reported.. Of 41 patients (36 males, 5 females; mean age: 60.8 years old) who received 4 courses of chemotherapy, 40 underwent total mesorectal excision, and 1 underwent total pelvic exenteration. R0 resection was achieved in 40 patients, but none showed a pathological complete response. Twenty-nine patients received adjuvant chemotherapy for an average of 4 months. The 3 year recurrence-free survival and local recurrence rates in patients undergoing curable resection were 72.8% and 8.5%, respectively. cStage III patients with adjuvant chemotherapy had a significantly higher 3 year recurrence-free survival than those without adjuvant chemotherapy (76.6 vs. 40.0%, log-rank p = 0.03).. Four courses of mFOLFOX6 chemotherapy before surgery may be a promising treatment strategy for locally advanced rectal cancer. Adjuvant chemotherapy might be needed for cStage III patients, even after four courses of neoadjuvant mFOLFOX6.

Topics: Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Organoplatinum Compounds; Prospective Studies; Rectal Neoplasms

To evaluate the efficacy and safety of apatinib combined with FOLFIRI in the first-line treatment of advanced metastatic colorectal cancer (mCRC) and explore potential factors of efficacy.. Twenty mCRC patients treated at Affiliated Cancer Hospital of Shanxi Medical University from March 2017 to March 2019 were included according to the enrolment criteria. They provided informed consent and were treated with apatinib combined with FOLFIRI according to the scheduled regimen until disease progression or unacceptable toxicity occurred. The primary endpoint was OS. The secondary endpoints included PFS, ORR, DCRand safety. OS and PFS were calculated using Kaplan-Meier curves. Univariate and multivariate Cox regression analyses were used to evaluate independent prognostic factors of OS and PFS. R was used to determine cut-off values for biochemical indicators. Forest maps were drawn for Cox univariate results and the relationships between NLR and ECOG, which were significant in univariate analysis, and OS were represented by Kaplan-Meier curves.. The median OS and PFS were 16.135 months (95% CI: 9.211-22.929) and 6 months (95% CI: 5.425-6.525). Multivariate Cox analysis showed that NLR and CEA were independent prognostic factors. The most common grade 3-4 adverse events were hypertension, diarrhoea, increased alkaline phosphatase, decreased leukocytes and decreased neutrophils.. Apatinib combined with FOLFIRI for the first-line treatment of advanced unresectable mCRC showed good efficacy and safety. The baseline NLR was predictive of efficacy, and a low baseline NLR (HR: 0.2895, P = 0.0084) was associated with improved OS.Clinical Research Registration Number: ChiCTR1800015308.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Pyridines; Rectal Neoplasms

Little is known about the interaction of comorbidities and age on survival outcomes in colorectal cancer (mCRC), nor how comorbidities impact treatment tolerance.. We utilized a cohort of 1345 mCRC patients enrolled in CALGB/SWOG 80405, a multicenter phase III trial of fluorouracil/leucovorin + oxaliplatin (FOLFOX) or irinotecan (FOLFIRI) plus bevacizumab, cetuximab or both. Endpoints were overall survival (OS), progression-free survival (PFS), and grade ≥ 3 toxicities assessed using NCI CTCAE v.3.0. Participants completed a questionnaire, including a modified Charlson Comorbidity Index. Adjusted Cox and logistic regression models tested associations of comorbidities and age on the endpoints.. In CALGB/SWOG 80405, 1095 (81%) subjects were < 70 years and >70 250 (19%). Presence of ≥1 comorbidity was not significantly associated with either OS (HR 1.10, 95% CI 0.96-1.25) or PFS (HR 1.03, 95% CI 0.91-1.16). Compared to subjects <70 with no comorbidities, OS was non-significantly inferior for ≥70 with no comorbidities (HR 1.21, 95% CI 0.98-1.49) and significantly inferior for ≥70 with at least one comorbidity (HR 1.51, 95% CI 1.22-1.86). There were no significant associations or interactions between age or comorbidity with PFS. Comorbidities were not associated with treatment-related toxicities. Age ≥ 70 was associated with greater risk of grade ≥ 3 toxicities (OR 2.15, 95% CI 1.50-3.09, p < 0.001).. Among participants in a clinical trial of combination chemotherapy for mCRC, presence of older age with comorbidities was associated with worse OS but not PFS. The association of age with toxicity suggests additional factors of care should be measured in clinical trials.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colonic Neoplasms; Colorectal Neoplasms; Comorbidity; Fluorouracil; Humans; Leucovorin; Rectal Neoplasms; Treatment Outcome

To compare the efficacy and safety of folinic acid, fluorouracil and irinotecan (FOLFIRI) plus bevacizumab or aflibercept in metastatic colorectal cancer (mCRC) patients pretreated with oxaliplatin-based chemotherapy.. We analysed the treatment outcomes of patients receiving FOLFIRI in combination with bevacizumab or aflibercept as second-line treatment for mCRC between October 2017 and March 2020. This analysis included 67 patients receiving FOLFIRI plus aflibercept and 83 receiving FOLFIRI plus bevacizumab.. The overall response rate (ORR) was 13.6% (95% confidence interval 4.85-22.34) in the FOLFIRI-aflibercept group and 14.7% (95% confidence interval 6.68-22.71) in the FOLFIRI-bevacizumab group. This difference in ORR was not statistically significant. The median progression-free survival was 8.6 months in the FOLFIRI-bevacizumab group and 8.5 months in the FOLFIRI-aflibercept group (P = 0.752). Patients in the FOLFIRI-bevacizumab group showed a median overall survival of 12.4 months, whereas patients in the FOLFIRI-aflibercept group had a median overall survival of 13.7 months (P = 0.276). There were no significant differences in survival between the two treatment groups. The adverse events were also largely similar between the two groups. However, hypertension of grade 3 or more was more frequent in the FOLFIRI-aflibercept group.. FOLFIRI plus bevacizumab and FOLFIRI plus aflibercept had similar anti-tumour activities and toxicity profiles when used as second-line therapy in mCRC patients. Based on these data, both aflibercept and bevacizumab are suitable anti-angiogenic agents when used in combination with FOLFIRI for mCRC.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Humans; Irinotecan; Leucovorin; Neoplasm Metastasis; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Rectal Neoplasms

A 69-year-old female underwent laparoscopic ileal partial resection for ileal adenocarcinoma. Pathological diagnosis was moderately differentiated tubular adenocarcinoma (UICC 8th; T4N0M0 StageIIB). The patient received adjuvant chemotherapy with modified 5-fluorouracil/leucovorin/oxaliplatin. Fourteen months after surgery, computed tomography revealed a mass in the upper rectum. Colonoscopy detected a submucosal protruding mass and a biopsy specimen showed moderately differentiated tubular adenocarcinoma. Robotic low anterior resection was performed. The tumor was located in the upper rectum and there was no macroscopic invasion or peritoneal dissemination. Pathologically, the tumor was moderately differentiated tubular adenocarcinoma located within the rectal wall with little evidence of a carcinoma component in the mucosal lining. Immunohistochemistry showed the same pattern as the previous ileal adenocarcinoma: negativity for cytokeratin 7 and positivity for cytokeratin 20 and caudal-type homeobox 2. In combination with the rectum showing no abnormalities in colonoscopy performed 15 mo previously, the mass was considered hematogenous metastasis from small bowel adenocarcinoma.

Topics: Adenocarcinoma; Aged; Duodenal Neoplasms; Female; Fluorouracil; Humans; Keratin-20; Keratin-7; Leucovorin; Oxaliplatin; Rectal Neoplasms; Robotic Surgical Procedures

The VELOUR study showed the benefit of FOLFIRI-Aflibercept (FA) versus FOLFIRI in patients with metastatic colorectal cancer (mCRC) in second-line treatment. However, only 36% of the included patients were ≥65 years. Thus, we seek to evaluate the efficacy and safety of FA in the elderly population in the context of routine practice.. We conducted an observational, retrospective, multicenter, observational study of patients ≥70 years with mCRC treated with FA after progression to oxaliplatin chemotherapy in routine clinical practice in 9 hospitals of the GITuD group.. Of 388 patients treated with FA between June 2013 and November 2018, 75 patients ≥70 years were included. The median number of cycles was 10 and the objective response (ORR) and disease control rates (DCR) were 33.8% and 72.0%, respectively. With a median follow-up of 27.1 months, median Progression-free survival (PFS) was 6.6 months and median Overall Survival (OS) was 15.1 months. One third fewer metastasectomies were performed in the ≥75 years' subgroup (24 vs. 52%, p = 0.024) and more initial FOLFIRI dose reductions (68 vs. 36%, p = 0.014). ORR (23.8% vs. 38.3%), DCR (42.8% vs. 85.1%), and PFS (4 vs. 7.8 months; p = 0.017) were significantly less, without difference in OS (9.9 vs. 17.1 months; p = 0.129). The presence of prior hypertension (HT) (PFS 7.9 vs. 5.7 months, p = 0.049) and HT ≥ grade 3 during treatment (PFS 7.6 vs. 6.6 months, p = 0.024) were associated with longer PFS. The most frequent grade 3/4 adverse events were: asthenia (21.3%), neutropenia (14.7%), and diarrhea (14.7%). 57.3% required FOLFIRI dose reduction; 34.7% of aflibercept, including discontinuation (5.3% and 18.7%, respectively).. FA combination is effective in patients ≥70 years. The occurrence of HT is predictive of efficacy. Close monitoring of toxicity and initial dose adjustment is recommended.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Oxaliplatin; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Rectal Neoplasms; Retrospective Studies

Recent data suggest that BRAFV600E-mutated metastatic colorectal cancer (mCRC) patients with right-sided tumours and ECOG-PS = 0 may achieve benefit from the triplet regimen differently than those with left-sided tumours and ECOG-PS > 0.. The predictive impact of primary sidedness and ECOG-PS was evaluated in a large real-life dataset of 296 BRAFV600E-mutated mCRC patients treated with upfront triplet or doublet ± bevacizumab. Biological differences between right- and left-sided BRAFV600E-mutated CRCs were further investigated in an independent cohort of 1162 samples.. A significant interaction effect between primary sidedness and treatment intensity was reported in terms of both PFS (p = 0.010) and OS (p = 0.003), with a beneficial effect of the triplet in the right-sided group and a possible detrimental effect in the left-sided. No interaction effect was observed between ECOG-PS and chemo-backbone. In the MSS/pMMR population, a consistent trend for a side-related subgroup effect was observed when FOLFOXIRI ± bevacizumab was compared to oxaliplatin-based doublets±bevacizumab (p = 0.097 and 0.16 for PFS and OS, respectively). Among MSS/pMMR tumours, the BM1 subtype was more prevalent in the right-sided group (p = 0.0019, q = 0.0139). No significant differences were observed according to sidedness in the MSI-H/dMMR population.. Real-life data support the use of FOLFOXIRI ± bevacizumab only in BRAFV600E-mutated mCRC patients with right-sided tumours.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Organoplatinum Compounds; Rectal Neoplasms

Colorectal cancer is one of the most commonly diagnosed malignancies globally and nearly half of these patients develop metastatic colorectal cancer (mCRC). The current standard treatment for mCRC includes 5-fluorouracil-based chemotherapy with or without bevacizumab. Nevertheless, a predictive biomarker of efficacy for bevacizumab has not yet been firmly established. This retrospective study aimed to investigate the correlation between tumor calcification and prognosis in mCRC patients who received bevacizumab plus chemotherapy as the first-line treatment. The authors found that tumor calcification was independently associated with improved survival in mCRC patients treated with bevacizumab plus chemotherapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Rectal Neoplasms; Retrospective Studies

The activation of stimulator of interferon genes (STING) was reported to enhance cetuximab-mediated natural killer cell activation and dendritic cell maturation. Polymorphisms in genes in the cyclic GMP-AMP synthase (cGAS)-STING pathway may affect innate immune response. Therefore, we hypothesised that genetic variants in the cGAS-STING pathway may predict the efficacy of cetuximab-based treatment in patients with metastatic colorectal cancer.. Genomic DNA from blood samples of patients enrolled in FIRE-3 (cetuximab arm, n = 129; bevacizumab arm, n = 107) and TRIBE (bevacizumab arm, n = 215) was genotyped using the OncoArray-500K bead chip panel. Seven selected single nucleotide polymorphisms in 3 genes (cGAS, STING and interferon B1 (IFNB1)) were analysed for the association with overall survival and progression-free survival.. In the cetuximab cohort, patients with STING rs1131769 any T allele showed significantly shorter overall survival (36.3 versus 56.1 months) than carriers of C/C in both univariate [hazard ratio (HR) = 2.08; 95% confidence interval (CI): 1.06-4.07; P = 0.03] and multivariate (HR = 2.98; 95% CI: 1.35-6.6; P = 0.0085) analyses; patients carrying IFNB1 rs1051922 G/A and A/A genotype showed a significantly shorter progression-free survival than carriers of G/G allele in both univariate (G/A versus G/G, 10.2 versus 14.1 months, HR = 1.84; 95% CI 1.23-2.76; A/A versus G/G, 10.7 versus 14.1 months, HR = 2.19; 95% CI 0.97-4.96; P = 0.0077) and multivariate analyses (G/A versus G/G, HR = 2; 95% CI 1.22-3.3; A/A versus G/G, HR = 2.19, 95% CI 0.92-5.26, P = 0.02). These associations were not observed in the bevacizumab arm of FIRE-3 or TRIBE.. These results suggest for the first time that germline polymorphisms in STING and IFNB1 genes may predict the outcomes of cetuximab-based treatment in patients with metastatic colorectal cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Cetuximab; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Humans; Interferons; Leucovorin; Membrane Proteins; Nucleotidyltransferases; Rectal Neoplasms

Five-fluorouracil, folinic acid, oxaliplatin and irinotecan (FOLFOXIRI) regimen is used as the first-line treatment for metastatic colorectal cancer (mCRC). The use of capecitabine, an oral fluoropyrimidine pro-drug, is feasible and safe; hence, it provides an interesting alternative to 5-fluorouracil in the abovementioned regimen. This study aimed to evaluate the efficacy and safety of capecitabine, oxaliplatin, and irinotecan (XELOXIRI) regimen use with or without targeted drugs in Chinese patients with mCRC.. We conducted a retrospective, longitudinal cohort study of patients with mCRC who received XELOXIRI regimen with or without targeted drugs (bevacizumab or cetuximab) every 2 weeks between January 2017 and November 2019 at the National Cancer Center/Cancer Hospital, the Chinese Academy of Medical Sciences, and Peking Union Medical College. Treatment efficacy was assessed by investigators by evaluating the objective response rate (ORR) and disease control rate (DCR). Overall survival (OS) was assessed using Cox proportional hazards models. The adverse events were also analyzed.. Sixty-one consecutive patients were examined and followed up for survival. As of November 8, 2021, the median follow-up time was 35.4 months. Disease progression and death occurred in 50 (82%) and 38 (62%) patients, respectively. The median treatment duration of XELOXIRI with or without bevacizumab or cetuximab was 10 cycles (range, 1-12 cycles). The median OS and PFS were 32.2 months (95%CI [24.8-39.6]) and 9.3 months (95% CI [8.1-10.5]), respectively. The ORR of 48 patients with measurable lesions was 70.8%, and the DCR was 89.6%. RAS/BRAF wild-type (HR 0.39; 95% CI [0.16-0.96], p = 0.04) and metastatic organs > 2 (HR 3.25; 95% CI [1.34-7.87], p = 0.009) were independent prognostic factors for OS. The incidence of any grade of adverse events (AEs) was 96.7% (59/61). Grade ≥ 3 AEs included neutropenia (19.7%), leukopenia (9.8%), diarrhea (3.3%), vomiting (3.3%), febrile neutropenia (1.6%), and thrombocytopenia (1.6%). No treatment-related death occurred.. The use of the XELOXIRI regimen with or without a targeted drug was effective, with a manageable toxicity profile in Chinese patients with mCRC.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Capecitabine; Cetuximab; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Humans; Irinotecan; Leucovorin; Longitudinal Studies; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms; Retrospective Studies

In this retrospective study, the authors examined baseline characteristics of and treatment duration and real-world overall survival (rwOS) in 1096 and 684 patients with metastatic colorectal cancer receiving cetuximab as second-line (2L) and third-line (3L) treatment, respectively. The most common cetuximab-based regimens were cetuximab + folinic acid, fluorouracil and irinotecan (2L: 44%; 3L: 32%) and cetuximab + irinotecan (2L: 28%; 3L: 35%). Median treatment duration and rwOS were 3.7 and 14.4 months, respectively, in patients receiving treatment in the 2L cohort. In the 3L cohort, median treatment duration was 3.3 months and rwOS was 12.0 months. This large real-world study provides evidence of rwOS in patients with metastatic colorectal cancer receiving cetuximab-based regimens as 2L or 3L treatment.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cetuximab; Colonic Neoplasms; Colorectal Neoplasms; Fluorouracil; Humans; Irinotecan; Leucovorin; Rectal Neoplasms; Retrospective Studies

Although the current standard of care for patients with lower rectal cancer in Japan includes total mesorectal resection with lateral lymph node dissection, postoperative local and distant recurrence rates are high. Multidisciplinary treatment is important to improve the prognosis. A man in his 30s was diagnosed with lower rectal cancer due to bloody stool and referred to our department. He was diagnosed as cT3N3M0, cStage Ⅲc with right obturator lymph node metastasis. Four courses of neoadjuvant chemotherapy(NAC)with FOLFOXIRI plus cetuximab were performed. Because Grade 3 neutropenia was observed in the first cycle(CTCAE v5.0), pegfilgrastim was administered in the second and subsequent cycles, and NAC was completed without dose reduction. The patient underwent laparoscopy-assisted intersphincteric rectal resection and D3+rtLD2 dissection. Histopathological resection margins were negative, and the resection was R0. Lymph node metastasis was found only in No. 263d-rt, and the pathological diagnosis was ypT3N3M0, pStage Ⅲc. Histological evaluation of response to treatment was Grade 2. The postoperative course was good and the patient was discharged on postoperative day 15. The patient received 8 courses of adjuvant chemotherapy with mFOLFOX6 from the 7th postoperative week and is alive and recurrence-free 6 months after surgery.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cetuximab; Fluorouracil; Humans; Leucovorin; Male; Neoadjuvant Therapy; Organoplatinum Compounds; Rectal Neoplasms

An 80-year-old man underwent laparoscopic rectal high anterior resection with perineal dissemination for the management of RS rectal cancer. Following the diagnosis of RS rectal cancer with muc, pT4a, N3(14/15), M1c, P1, pStage Ⅳc, RAS/BRAF: wild type, treatment was initiated with mFOLFOX6 plus panitumumab(Pmab). Laboratory examination on admission revealed mild renal dysfunction(Cr 1.45 mg/dL). The patient became confused on day 3 of chemotherapy(JCS Ⅲ-200). Furthermore, laboratory findings revealed a serum ammonia level of 338μg/dL. He was diagnosed with 5-FU- induced hyperammonemic encephalopathy. Discontinuation of high-dose 5-FU and branched-chain amino acid solutions improved his mental status and decreased serum ammonia levels. We switched his chemotherapy regime to CPT-11 plus Pmab, but it was discontinued after 1 course on his request.

Topics: Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Brain Diseases; Fluorouracil; Humans; Leucovorin; Male; Panitumumab; Rectal Neoplasms

A 75-year-old man was diagnosed with advanced rectal cancer infiltrating the bladder and a single metastatic liver tumor. The patient first underwent colostomy followed by 8 cycles of chemotherapy, using a regimen of cetuximab, calcium levofolinate hydrate, fluorouracil and oxaliplatin(Cmab plus mFOLFOX6). This treatment resulted in a partial response(PR). Five months after the first operation, laparoscopic partial hepatectomy(S4), low anterior resection and ileostomy by laparotomy were performed. The pathological findings were T4b, N1b, M1a, H1, ypStage Ⅳa and all surgical margins were negative, so R0 resection was performed for preservation of bladder function. The patient received adjuvant chemotherapy and has survived without recurrence for 10 months after the second operation. The preoperative chemotherapy permitted combined resection of the bladder and urostomy. This is important because a double stoma commonly reduces quality of life. Thus, Cmab plus mFOLFOX6 may be useful as preoperative chemotherapy to preserve bladder function and quality of life.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Neoadjuvant Therapy; Quality of Life; Rectal Neoplasms; Urinary Bladder

A woman in her 30s visited our hospital complaining primarily of melena. Colonoscopy revealed the presence of a type 1 tumor in 2 cm from anal verge. Contrast-enhanced CT showed an unresectable massive liver metastasis in the left lobe of the liver and another metastasis in the right lobe. The patient received front-line chemotherapy with Leucovorin, fluorouracil, oxaliplatin, and irinotecan(FOLFOXIRI)plus bevacizumab(BEV). A year later, a marked reduction of liver metastases and primary lesions was confirmed by CT scan imaging. A multidisciplinary team recommended resection of the liver metastases followed by laparoscopic intersphincteric resection for primary lesions. However, after 1 year, a recurrence was diagnosed in the liver; hence, FOLFOXIRI plus BEV was reintroduced for volume reduction. The patient underwent a repeat hepatectomy since enough volume reduction was confirmed. One year later, she experienced a re-relapse of the metastasis in the liver. Currently, she is still undergoing chemotherapy following 7 years since the first visit. Long-term survival can be expected following surgical treatment during chemotherapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colorectal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Neoplasm Recurrence, Local; Organoplatinum Compounds; Rectal Neoplasms

Portal vein thrombosis (PVT) while using an angiogenesis inhibitor is relatively rare. A 70-year-old Asian man was diagnosed with PVT two months after initiating 5-fluorouracil/leucovorin, irinotecan, and bevacizumab therapy for rectal cancer with liver metastases. Because the metastases were small and shrinking, we suspected that the thrombosis might have been caused by bevacizumab-containing chemotherapy. We stopped bevacizumab and started apixaban, a direct oral anticoagulant (DOAC). Eight months later, the complete dissolution of the thrombus and recanalization of the portal vein were attained. Our case suggests that PVT can occur during bevacizumab-containing chemotherapy, and DOAC therapy might be beneficial for treating PVT in patients with cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Male; Portal Vein; Pyrazoles; Pyridones; Rectal Neoplasms

Neoadjuvant chemotherapy to treat locally advanced rectal cancer is an effective therapeutic strategy for the prevention of local recurrence and distant organ metastasis after surgery.. To assess the prognostic significance of histopathological tumor response in rectal cancer patients undergoing neoadjuvant chemotherapy.. This study included patients with operable rectal cancer who received neoadjuvant chemotherapy using the FOLFOX regimen (5-fluorouracil, l-leucovorin, and oxaliplatin) in a hospital between February 2012 and November 2017. The main outcome measure was disease-free survival with respect to histopathological response to neoadjuvant chemotherapy in resected specimens.. The median follow-up was 32 months. Of 48 patients treated with neoadjuvant FOLFOX, 24 (50%) were classified as responders, which included two patients with pathological complete response and 22 patients with partial response. The remaining 24 patients (50%) were classified as nonresponders. Responders had a significantly better 3-year disease-free survival than nonresponders (86% vs. 62%, p = .02).. Patients whose surgical specimens show a pathological complete response or partial response have good oncologic outcomes.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials, Phase II as Topic; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Oxaliplatin; Prognosis; Prospective Studies; Rectal Neoplasms; Retrospective Studies; Survival Rate

Administration of chemotherapeutic regimens such as FOLFOX or CAPEOX with chemoradiation in the neoadjuvant setting, termed total neoadjuvant treatment (TNT), was introduced in recent years. By increasing the complete pathologic and clinical responses, patients with locally advanced rectal cancer may have better oncologic outcomes and potentially abstain from undergoing a proctectomy.. All patients who underwent TNT at a single National Accreditation Program for Rectal Cancer accredited referral center were included. A retrospective analysis was performed using a computerized Institutional Review Board-approved database. Patient demographics, diagnostic workup, treatment regimens, and surgical and pathological reports were reviewed. Complete pathological response was the primary outcome. Univariable and multivariable logistic regression analyses were performed to identify potential factors predisposing to complete pathological response.. Thirty patients met the inclusion criteria, 14(46.6%) of whom had complete pathologic response. There was no difference in baseline demographic characteristics between patients who achieved complete pathological response and those who did not. Pathology revealed a 92% intact mesorectum rate in the complete pathologic response group and a mean of 24 harvested lymph nodes in the entire study cohort. Both univariable and multivariable logistic regression analyses failed to demonstrate statistically significant factors predicting complete pathologic response, magnetic resonance imaging (MRI) tumor size, and posttreatment MRI lymph node positivity.. TNT is safe and efficient for patients with locally advanced rectal cancer. It increases complete pathological and clinical response rates and may more widely evolve to be the treatment of choice in this group of patients in the near future.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Female; Fluorouracil; Humans; Leucovorin; Logistic Models; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Rectal Neoplasms; Retrospective Studies; Treatment Outcome

Elevated pretreatment carcinoembryonic antigen (CEA) levels are related to poor prognosis in patients with locally advanced rectal cancer (LARC) treated with neo-CRT followed by TME. In patients with normal pretreatment CEA levels, the prognostic significance of carbohydrate antigen 199 (CA199) is controversial.. The aim of this study was to explore the prognostic value of pretreatment serum CA199 in patients with LARC who had normal pretreatment CEA levels treated with neo-CRT followed by curative surgery.. A retrospective study of 456 patients with LARC treated with neo-CRT followed by TME between January 2006 and May 2017 was performed. We employed the maximal χ2 method to determine the CA199 threshold of 9.1 U/mL based on the difference in survival and divided patients into 2 groups. Group 1: patients with pretreatment s-CEA < 5 ng/mL and CA199 ≥ 9.1 U/mL. Group 2: patients with pretreatment s-CEA < 5 ng/mL and CA199 < 9.1 U/mL. Overall survival (OS) across CA199 was assessed using Cox proportional hazard regression models (PS:CEA ≥ 5 ng/mL was seen as elevated).. Multivariate analyses demonstrated that the following factors were significantly related to OS in patients with LARC with normal pretreatment CEA levels: ypT (odds ratio [OR] 1.863, p = 0.030), ypN (OR 1.622, p = 0.026), and pretreatment CA199 levels (OR 1.886, p = 0.048).. Pretreatment CA199 is an independent factor for OS in patients with LARC with normal pretreatment CEA levels, which may reach the clinic to guide individualized decision-making.

Topics: Adenocarcinoma; Aged; Antigens, Tumor-Associated, Carbohydrate; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Capecitabine; Carcinoembryonic Antigen; Chemoradiotherapy, Adjuvant; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaliplatin; Proctectomy; Prognosis; Rectal Neoplasms; Retrospective Studies

We present a case of locally advanced rectal cancer(LARC)treated by robot assisted intersphincteric resection(ISR)and lateral lymph node dissection(LLND)after neoadjuvant chemotherapy(NAC). The patient was a 69-year-old female with the diagnosis of adenocarcinoma of the rectum Rb. The clinical stage diagnosis was cT3N0M0, cStage Ⅱ. NAC with FOLFOXIRI(5-fluorouracil/oxaliplatin/leucovorin/irinotecan)plus bevacizumab(BEV)was inisiated as NAC. Tumor volume reduction of primary lesion was evaluated by CT scan and colonoscopy after 6 courses of FOLFOXIRI plus BEV including omit of BEV on last course and were judged as partial response(PR)and no distant metastasis. With maintenance of tolerability for surgery even after NAC, robot assisted ISR and LLND were safely performed with curative resection. The histopathological treatment effect of post NAC was diagnosed as Grade 1b and the final pathological stage was ypT3pN0cM0, ypStage ⅡA. We experienced a case of LARC was performed FOLFOXIRI plus BEV as NAC followed by robotic ISR and LLND with anal preservation.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Leucovorin; Neoadjuvant Therapy; Rectal Neoplasms; Rectum; Robotics

We herein report a woman who was suffering from type 1 diabetes and hearing impairment and whose mother had mitochondrial disease. Abdominal ultrasound identified a hepatic tumour, and a further examination led to the diagnosis of rectal cancer with synchronous multiple liver metastases. A genetic test led to the diagnosis of mitochondrial disease with a mitochondrial gene 3243A>G mutation. After neoadjuvant chemotherapy, we performed hepatectomy and low anterior resection in one stage. Hepatic vascular exclusion was not performed in order to prevent damage to hepatocytes due to liver ischaemia, and Ringer's lactate solution was not used to prevent lactic acidosis. The postoperative course was uneventful. Only one other case involving hepatectomy being performed in a patient with mitochondrial disease has been reported. Considering the extreme rarity of such cases and the importance of perioperative management, we report this case here.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Diabetes Mellitus, Type 2; Female; Fluorouracil; Hepatectomy; Humans; Leucovorin; Liver Neoplasms; Mitochondrial Diseases; Organoplatinum Compounds; Pedigree; Rectal Neoplasms

We analyzed the safety and feasibility of preoperative short-course radiotherapy (SCRT) followed by consolidation chemotherapy for patients with locally advanced rectal cancer (LARC).. From April 2018 to May 2019, 19 patients with LARC were treated with SCRT followed by three cycles of consolidation chemotherapy with leucovorin, fluorouracil, and oxaliplatin (FOLFOX6) before surgery. Adjuvant chemotherapy relied on oxaliplatin. Tumor response, patient compliance, and toxicities were analyzed.. The median age was 60 years (range 44-71), and 16 of the patients were male. The median tumor height was 5 cm (range 0-9) from anal verge. All patients received a total dose of 25 Gy in five fractions. The number of cycles of FOLFOX6 before surgery was three in 17, four in one, five in one. Five patients required dose reductions in consolidation chemotherapy. The median interval between initiation of SCRT and surgery was 10.6 weeks (range 8.6-16.4). A pathologic complete response was seen in two patients (11%). Grade III toxicities to the preoperative treatment were seen in five patients (26%): diarrhea in two, a decreased white blood cell count in one, and anemia in two. Postoperative complications arising within 30 days developed in five patients (26%). During the median follow-up period of 20.4 months, there was no tumor recurrence.. Preoperative SCRT followed by oxaliplatin-based consolidation chemotherapy showed acceptable toxicity and feasibility in patients with LARC. Prospective randomized trials are warranted to verify the efficacy and safety of this treatment strategy compared with conventional long-course concurrent chemoradiotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Consolidation Chemotherapy; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Oxaliplatin; Prospective Studies; Rectal Neoplasms

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Carcinoembryonic Antigen; Chemoradiotherapy; Fluorouracil; Humans; Induction Chemotherapy; Leucovorin; Magnetic Resonance Imaging; Male; Neoadjuvant Therapy; Neoplasm Invasiveness; Neoplasm Staging; Neoplasm, Residual; Organ Sparing Treatments; Organoplatinum Compounds; Proctectomy; Rectal Neoplasms

Sexual dysfunctions seriously affect the quality of life of patients. The aim of this study was to identify the risk factors for sexual dysfunction after rectal cancer surgery.. A total of 948 consecutive patients undergoing rectal cancer radical resection were included between January 2012 and August 2019. The sexual functions were evaluated by the 5-item version of the International Index of Erectile Function (IIEF-5) in men and Index of Female Sexual Function (IFSF) in women at 12 months postoperatively.. Postoperative sexual dysfunction was observed in 228 patients with rectal cancer (24.05%), which included 150 cases in male patients (25.0%) and 78 cases in female patients (22.5%). A multivariate logistic regression analysis results showed that age ≥45 years old (OR = 1.72, p = 0.001), tumor below the peritoneal reflection (OR = 1.64, p = 0.005), receiving preoperative radiotherapy (OR = 4.12, p < 0.001) and undergoing abdominoperineal resection (APR), intersphincteric resection (ISR) and Hartmann surgery (OR = 2.43, p < 0.001) were the independent risk factors of sexual dysfunction for patients with rectal cancer.. Age ≥45 years old, tumors below the peritoneal reflection, receiving preoperative radiotherapy, and undergoing APR, ISR and Hartmann surgery were the independent risk factors of sexual dysfunction. Patients should be informed about the sexual dysfunctions in the pre-operative consultations. More attention should be paid to intraoperative pelvic autonomic nerve preservation on rectal cancer patients with these risk factors for clinic surgeons.

Topics: Adenocarcinoma; Adult; Age Factors; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemotherapy, Adjuvant; Digestive System Surgical Procedures; Female; Fluorouracil; Humans; Leucovorin; Logistic Models; Male; Middle Aged; Multivariate Analysis; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaliplatin; Postoperative Complications; Proctectomy; Prospective Studies; Radiotherapy; Rectal Neoplasms; Risk Factors; Sexual Dysfunction, Physiological

FOLFOX is a standard chemotherapy regimen used to treat colorectal cancer. Adverse events associated with FOLFOX treatment include peripheral neuropathy and myelosuppression. This report discusses the case of a 64-year-old man with rectal cancer who developed hyperammonemia and impaired consciousness following initiation of mFOLFOX6 as a postoperative adjuvant therapy.. This case study reports on the clinical disease progression of the aforementioned patient.. Although impaired consciousness is a rare adverse reaction of FOLFOX, it has a major psychological impact on the patient and his/her family. Hyperammonemia should therefore be considered a potential cause of impaired consciousness during FOLFOX therapy and should be appropriately diagnosed and treated.

Topics: Antineoplastic Combined Chemotherapy Protocols; Consciousness; Female; Fluorouracil; Humans; Hyperammonemia; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Rectal Neoplasms

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Fluorouracil; Humans; Irinotecan; Leucovorin; Neoadjuvant Therapy; Oxaliplatin; Pancreatic Neoplasms; Rectal Neoplasms

A prognostic benefit of additive chemotherapy in patients following resection of metachronous colorectal liver metastases (CRLM) remains controversial. Therefore, the goal of this retrospective study was to investigate the impact of perioperative chemotherapy on disease-free survival (DFS) and overall survival (OS) of patients after curative resection of metachronous CRLM.. In a retrospective single-centre study, patients after curative resection of metachronous CRLM were included and analysed for DFS and OS with regard to the administration of additive chemotherapy. The Kaplan-Meier method was applied to compare DFS and OS while Cox regression models were used to identify independent prognostic variables.. Thirty-four of 75 patients were treated with additive 5-FU based chemotherapy. OS was significantly prolonged in this patient subgroup (62 vs 57 months; p = 0.032). Additive chemotherapy significantly improved 10-year survival rates (42% vs 0%, p = 0.023), but not 5-year survival (58% vs 42%, p = 0.24). Multivariate analysis identified additive chemotherapy (p = 0.016, HR 0.44, 95% CI 0.23-0.86), more than five CRLM (p = 0.026, HR 2.46, 95% CI 1.16-10.32) and disease recurrence (0.009, HR 2.70, 95% CI 1.29-5.65) as independent risk factors for OS.. Additive chemotherapy significantly prolonged OS and 10-year survival in patients after curative resection of metachronous CRLM. Randomized clinical trials are needed in the future to identify optimal chemotherapy regimens for those patients.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Capecitabine; Chemotherapy, Adjuvant; Colonic Neoplasms; Disease-Free Survival; Female; Fluorouracil; Hepatectomy; Humans; Kaplan-Meier Estimate; Leucovorin; Liver Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Prognosis; Proportional Hazards Models; Rectal Neoplasms; Retrospective Studies; Risk Factors; Survival Rate; Time Factors

The addition of induction chemotherapy (ICT) to neoadjuvant chemoradiotherapy (CRT) has the potential to improve outcomes in patients with locally advanced rectal cancer (LARC). However, patient selection is essential to prevent overtreatment. This study compared the complete response (CR) rate after treatment with and without ICT of LARC patients with prognostically poor characteristics.. All LARC patients who were treated with neoadjuvant CRT, whether or not preceded by ICT, and who underwent surgery or were considered for a wait-and-see strategy between January 2016 and March 2020 in the Catharina Hospital Eindhoven, were retrospectively selected. LARC was defined as any T4 tumour, or a T2/T3 tumour with extramural venous invasion and/or tumour deposits and/or N2 lymph node status, and/or mesorectal fascia involvement (T3 tumours only). Case-control matching was performed based on the aforementioned characteristics.. Of 242 patients, 178 (74%) received CRT (CRT-group) and 64 patients (26%) received ICT followed by CRT (ICT-group). In the ICT-group, 3 patients (5%) did not receive the minimum of three cycles. In addition, in this selected cohort, compliance with radiotherapy was 100% in the ICT-group and 97% in the CRT-group. The CR rate was 30% in the ICT-group and 15% in the CRT-group (p = 0.011). After case-control matching, the CR rate was 28% and 9%, respectively (p = 0.013).. Treatment including ICT seemed well tolerated and resulted in a high CR rate. Hence, this treatment strategy may facilitate organ preservation and improve survival in LARC patients with prognostically poor characteristics.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Capecitabine; Case-Control Studies; Dose Fractionation, Radiation; Fascia; Female; Fluorouracil; Humans; Induction Chemotherapy; Leucovorin; Lymphatic Metastasis; Magnetic Resonance Imaging; Male; Neoadjuvant Therapy; Neoplasm Invasiveness; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Prognosis; Rectal Neoplasms; Response Evaluation Criteria in Solid Tumors; Retrospective Studies; Treatment Outcome; Tumor Burden; Watchful Waiting

A 49-year-old male carcinoma rectum patient was treated with neoadjuvant FOLFOX (folinic acid, fluorouracil (5-FU) and oxaliplatin) chemotherapy, chemoradiotherapy with capecitabine, surgery and adjuvant FOLFOX. On follow-up, the patient developed a metabolically active liver lesion mimicking metastasis. Liver biopsy and histopathology showed sinusoidal dilatation with non-caseating granulomas. Follow-up fluorodeoxyglucose positron-emission tomography CT scan demonstrated increase in size of the lesion with metabolic activity suspicious of metastasis. The patient underwent segmental liver resection and histopathology showed non-necrotising granuloma with no evidence of malignancy. It is crucial to consider potential side effects of chemotherapeutic agents and have an unbiased approach when evaluating new liver lesions during post treatment follow-up of colorectal cancer. A multidisciplinary tumour board approach comprising of gastroenterologists, medical oncologists, pathologists, radiologists and surgeons is suggested in the management of such patients. The patient is currently doing well and on regular follow-up.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemical and Drug Induced Liver Injury; Diagnosis, Differential; Fluorouracil; Granuloma; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Rectal Neoplasms

Despite improvements in the multimodality treatment for patients with locally recurrent rectal cancer (LRRC), oncological outcomes remain poor. This study evaluated the effect of induction chemotherapy and subsequent chemo(re)irradiation on the pathologic response and the rate of resections with clear margins (R0 resection) in relation to long-term oncological outcomes.. All consecutive patients with LRRC treated in the Catharina Hospital Eindhoven who underwent a resection after treatment with induction chemotherapy and subsequent chemo(re)irradiation between January 2010 and December 2018 were retrospectively reviewed. Induction chemotherapy consisted of CAPOX/FOLFOX. Endpoints were pathologic response, resection margin and overall survival (OS), disease free survival (DFS), local recurrence free survival (LRFS), and metastasis free survival (MFS).. A pathologic complete response was observed in 22 patients (17%), a "good" response (Mandard 2-3) in 74 patients (56%), and a "poor" response (Mandard 4-5) in 36 patients (27%). An R0 resection was obtained in 83 patients (63%). The degree of pathologic response was linearly correlated with the R0 resection rate (p = 0.026). In patients without synchronous metastases, pathologic response was an independent predictor for LRFS, MFS, and DFS (p = 0.004, p = 0.003, and p = 0.024, respectively), whereas R0 resection was an independent predictor for LRFS and OS (p = 0.020 and p = 0.028, respectively).. Induction chemotherapy in addition to neoadjuvant chemo(re)irradiation is a promising treatment strategy for patients with LRRC with high pathologic response rates that translate into improved oncological outcomes, especially when an R0 resection has been achieved.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Combined Modality Therapy; Female; Fluorouracil; Humans; Induction Chemotherapy; Leucovorin; Male; Margins of Excision; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Organoplatinum Compounds; Oxaliplatin; Proctectomy; Rectal Neoplasms; Reoperation; Retrospective Studies; Survival Analysis; Treatment Outcome

A 65-year-old male was diagnosed with rectal cancer invading the urinary bladder, swollen para-aorticlymph nodes, and multiple liver metastases in abdominal CT. After 8 courses of mFOLFOX6 plus panitumumab, the rectal cancer, para-aortic lymph nodes metastasis, and liver metastases decreased significantly in size. Rectal cancer and liver metastases were considered resectable, hence low anterior resection of the rectum was performed. Intraoperative frozen section analysis showed negative metastaticinvolvement of the para-aorticlymph nodes and surgical margins of the urinary bladder; therefore, the urinary bladder was completely preserved. Partial resection of the liver was performed 2 months later. In conclusion, the patient showed good surgical and quality of life results. Thus, the bladder-sparing strategy with preoperative chemotherapy could be considered for appropriately selected rectal cancer patients with urinary bladder involvement.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Leucovorin; Male; Neoadjuvant Therapy; Quality of Life; Rectal Neoplasms; Urinary Bladder

A 69-year-old man with dyschezia was diagnosed with locally advanced colorectal cancer invading the urinary bladder and pelvis. We performed ileostomy to avoid passage disturbance because curative resection was difficult. The patient received 2 courses of modified FOLFOXIRI plus bevacizumab. The size of the primary tumor and lymph nodes decreased after chemotherapy. High anterior resection with D3 lymph node dissection was performed. Histopathological analysis revealed that the tumor stage was pT3, N0, M0, StageⅡ. The patient has been receiving adjuvant chemotherapy with oral UFT/UZEL for 6months. No recurrence has been observed for the past 4 months.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Fluorouracil; Humans; Leucovorin; Male; Neoplasm Recurrence, Local; Organoplatinum Compounds; Rectal Neoplasms

Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Fluorouracil; Humans; Leucovorin; Organoplatinum Compounds; Rectal Neoplasms; Retreatment

Treatment options for locally advanced rectal cancer have continued to consist largely of chemotherapy, chemoradiation, and/or surgical resection. For patients who are unable to undergo these therapeutic modalities or who do not to experience a response to them, treatment options are limited. We report 3 cases of mismatch repair-deficient (dMMR) locally advanced adenocarcinoma of the rectum that showed significant response with neoadjuvant immunotherapy-based systemic treatment. The first patient was not eligible for standard therapy because of a history of radiotherapy to the prostate with concurrent comorbidities and therefore received single-agent pembrolizumab. The second patient did not respond to total neoadjuvant chemoradiation and subsequently received combined nivolumab and ipilimumab. The third patient had a known family history of Lynch syndrome and presented with locally advanced rectal cancer and a baseline carcinoembryonic antigen level of 1,566 ng/mL. She was treated using neoadjuvant pembrolizumab and FOLFOX (folinic acid, fluorouracil, oxaliplatin). In this small series, we suggest that single-agent and combined-modality neoadjuvant immunotherapy/chemotherapy appear to be safe and effective treatment options for patients with (dMMR) locally advanced rectal cancer. Our findings encourage further studies to investigate the role of neoadjuvant immunotherapy as a viable treatment strategy in this population.

Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Chemoradiotherapy; Colorectal Neoplasms; Female; Fluorouracil; Humans; Immunotherapy; Ipilimumab; Leucovorin; Male; Neoadjuvant Therapy; Neoplastic Syndromes, Hereditary; Nivolumab; Organoplatinum Compounds; Rectal Neoplasms

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Brain Diseases; Female; Fluorouracil; Humans; Leucovorin; Medical Illustration; Organoplatinum Compounds; Rectal Neoplasms

A 65-year-old man underwent colonoscopy to evaluate rectal bleeding and was found to have a low rectal mass. Biopsy revealed moderately differentiated microsatellite stable adenocarcinoma. The tumor was palpable at the fingertip in the anterior rectum with the inferior border 5 cm from the anal verge by rigid proctoscopy. CEA was 0.8 ng/mL. CT imaging of the chest, abdomen, and pelvis showed no evidence of distant metastases. MRI confirmed a 5-cm mass with one 8-mm mesorectal lymph node metastasis and no extramural venous invasion. The tumor penetrated the mesorectal fat to a depth of 4 mm, and the circumferential margin was estimated to be 1 mm from the tumor (). He was presented at the multidisciplinary tumor board conference and interviewed and examined at the multidisciplinary clinic. He was dismayed at the prospect of his surgical options, a low anterior resection versus abdominoperineal resection, and wished to keep the options for organ preservation available. Standard long-course chemoradiation was initiated, with resolution of his bleeding after 2 weeks. He then completed 6 cycles of folinic acid, fluorouracil, and oxaliplatin (FOLFOX) chemotherapy (consolidation total neoadjuvant therapy (TNT)). The tumor was no longer palpable on office examination. A complete clinical response (cCR) was confirmed by flexible sigmoidoscopy () and MRI (). He was entered into the nonoperative management program with intense surveillance scheduling and has no evidence of recurrent disease almost 2 years after completion of TNT.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Colectomy; Fluorouracil; Humans; Leucovorin; Lymph Nodes; Magnetic Resonance Imaging; Male; Mesentery; Neoadjuvant Therapy; Neoplasm Invasiveness; Neoplasm Staging; Organ Sparing Treatments; Organoplatinum Compounds; Proctectomy; Rectal Neoplasms; Remission Induction; Watchful Waiting

The need to remove palliative primary tumors in the incurable Stage Ⅳ colorectal cancer patients remains debatable. Here, we describe the case of a 62-year-old man diagnosed with rectal cancer(cT3N2bM1b, cStage Ⅳb)with both primary tumor and metastatic lesions that were unresectable. Systemic chemotherapy was administered with 5-fluorouracil, Leucovorin, and oxaliplatin(FOLFOX)or FOLFOX with bevacizumab(BEV). After 12 months of treatment, CT scan revealed that both the primary tumor and metastases had shrunk significantly, leading to the conclusion that the primary tumor was resectable. Subsequently, laparoscopic abdominoperineal resection was performed. The patient was discharged 21 days postoperatively, and chemotherapy(FOLFOX plus BEV)was reintroduced 24 days after discharge. The patient was alive 25 months after the first consultation. Palliative primary tumor resection involves risks of operative complications and tumor progression owing to the absence of chemotherapy; however, some recent evidence has shown that primary tumor resection was associated with better prognosis and could be a good option on an individual patient basis. Further studies are required to establish the optimal strategy for patients with Stage Ⅳ colorectal cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colorectal Neoplasms; Fluorouracil; Humans; Laparoscopy; Leucovorin; Liver Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Proctectomy; Rectal Neoplasms

Polymorphic variants in IL-17A gene were differentially associated with colorectal cancer (CRC) susceptibility but their link with response and toxicity to CRC treatment have not yet been evaluated. We investigated association between seven IL-17A variants with the response and toxicity to CRC treatment in 294 patients with CRC. IL-17A genotyping was done by real-time PCR. MAF of rs3748067 was significantly higher in CRC cases resistant to FOLFOX treatment (R+) than non resistant (R-). Significantly higher rs3804513 MAF was noted in R+ versus R- colon cancer (CC). Higher rs2275913 and rs10484879, and reduced rs3804513 MAF were seen in rectal cancer (RC) tolerant to FOLFOX (T+) compared to (T-) patients. Strong association of rs3819025, rs3804513, and rs7747909 was found with tolerance to RC treatment. rs3748067 was associated with FOLFOX tolerance in CC but not RC. Significant higher frequency of AGGCAGG and GAGCAGG haplotypes was seen among R + CC, thus assigning non-favorable nature to these haplotypes. Higher and lower frequencies of GAGTAAG and AGGCTGA haplotypes, respectively, were observed in T + RC, thereby assigning FOLFOX-tolerant and non-tolerant nature to these haplotypes. The obtained results suggest that IL-17A variants and haplotypes may be a target for future management of CRC treatment.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Cross-Sectional Studies; Drug Resistance, Neoplasm; Female; Fluorouracil; Genotyping Techniques; Humans; Interleukin-17; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Polymorphism, Single Nucleotide; Rectal Neoplasms; Retrospective Studies; Treatment Outcome

A 72-year-old man was admitted to the hospital with fatigue. Colonoscopy revealed a 50 × 50 mm rectal tumor with bleeding. Based on close inspection, he was diagnosed with unresectable advanced rectal cancer with multiple liver metastases. Chemotherapy was administered as 10 cycles of bevacizumab + mFOLFOX6 and 7 cycles of bevacizumab + FOLFIRI. Nine months later, he presented with hematochezia and progression of anemia. It was difficult to stop the bleeding via endoscopy. He underwent radiation therapy (39 Gy in 13 fractions), and hemostasis was confirmed. Then, further chemotherapy was performed with 3 cycles of bevacizumab + FOLFIRI and 2 cycles of TAS102. However 14 months after the initial visit, he presented with right hypochondralgia and abdominal fullness due to the progression of multiple liver metastases. Palliative low-dose whole-liver radiation therapy (WLRT) (30 Gy in 10 fractions) was performed. He developed Grade 2 nausea, but his right hypochondralgia reduced, liver dysfunction improved, and he successfully completed radiotherapy. At approximately the same time his anemia progressed, and colonoscopy revealed recurrent bleeding from the tumor. Re-irradiation (15 Gy in 5 fractions) of the rectal tumor was carried out and a blood transfusion was performed for the bleeding. He was discharged after confirmation the anemia had not progressed. Few reports have been published on the use of both palliative re-irradiation to stop bleeding from rectal cancer and palliative low-dose WLRT. Based on our experience with this case, we believe that palliative radiotherapy can be useful in treating patients with a poor prognosis.

Topics: Abdominal Pain; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Disease Progression; Fluorouracil; Gastrointestinal Hemorrhage; Hemostasis; Humans; Leucovorin; Liver Neoplasms; Male; Organoplatinum Compounds; Palliative Care; Radiotherapy; Radiotherapy Dosage; Rectal Neoplasms; Treatment Outcome

Aflibercept plus 5-fluorouracil/levofolinate/irinotecan (FOLFIRI) is a second-line treatment for metastatic colorectal cancer. This ancillary exploratory analysis of data in Japanese people was aimed at exploring the relationship between a set of potential prognostic biomarkers and efficacy endpoints following aflibercept plus FOLFIRI therapy. Sixty-two patients with metastatic colorectal cancer received aflibercept (4 mg/kg) plus FOLFIRI every 2 weeks. Seventy-eight potential protein biomarkers were chosen for analysis based on their roles in angiogenesis, tumor progression, and tumor-stroma interaction. Plasma levels of biomarkers at baseline and at pre-dose 3 (day 1 of treatment cycle 3) were measured in all patients by ELISA. Relationships between these levels and efficacy endpoints were assessed. Ten potential biomarkers had a ±30% change from baseline to pre-dose 3 (adjusted P < .001), with the greatest changes occurring in placental growth factor (median: +4716%) and vascular endothelial growth factor receptor 1 (+2171%). Baseline levels of eight potential biomarkers correlated with overall survival in a univariate Cox regression analysis: extracellular newly identified receptor for advanced glycation end-products binding protein, insulin-like growth factor-binding protein 1, interleukin-8, kallikrein 5, pulmonary surfactant-associated protein D, tissue inhibitor of metalloproteinases 1, tenascin-C, and tumor necrosis factor receptor 2. None correlated with progression-free survival or maximum tumor shrinkage. Pre-dose 3 levels did not correlate with any efficacy endpoints. Preliminary data show that these eight biomarkers could be associated with overall survival. ClinicalTrials.gov identifier: NCT01882868.

Topics: Antineoplastic Combined Chemotherapy Protocols; Asian People; Biomarkers, Tumor; Camptothecin; Colonic Neoplasms; Fluorouracil; Humans; Insulin-Like Growth Factor Binding Protein 1; Interleukin-8; Japan; Kallikreins; Leucovorin; Placenta Growth Factor; Prognosis; Progression-Free Survival; Prospective Studies; Pulmonary Surfactant-Associated Protein D; Receptor for Advanced Glycation End Products; Receptors, Tumor Necrosis Factor, Type II; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Rectal Neoplasms; Regression Analysis; Tenascin; Tissue Inhibitor of Metalloproteinase-1; Vascular Endothelial Growth Factor Receptor-1

A 65-year-old woman was diagnosed with simultaneous hepatic metastasis of rectal cancer with portal venous tumor thrombi(Vp3)that developed in the bifurcation of the portal vein. Four days from the first visit, abdominal dynamic contrastenhanced CT image on the portal venous phase shows that the tumor thrombi progressed in the main trunk of the portal vein (Vp4). We decided that it was a condition of oncologic emergency and initiated FOLFOXIRI plus BV therapy. After 12 courses, tumor shrinkage and regression of the portal venous tumor thrombi were achieved, but conversion surgery was impossible because the collateral circulation of the hepatic portal region remained. The treatment target was changed to the extension of the survival period. The initiation and reinitiation of FOLFOXIRI plus BV therapy and maintenance of 5-FU/l-LV plus BV therapy contributed to disease control in 24 months and survival period of 36months.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Female; Fluorouracil; Hepatectomy; Humans; Leucovorin; Liver Neoplasms; Organoplatinum Compounds; Portal Vein; Rectal Neoplasms; Venous Thrombosis

There is a lack of large studies focusing on the prognostic significance of lateral lymph node (LLN) metastasis following LLN dissection (LLND) in rectal cancer. The aim of this study was to evaluate the prognostic impact of LLN metastases on survival of patients with advanced low rectal cancer.. Consecutive patients with locally advanced, but not metastatic, extraperitoneal rectal cancer treated with neoadjuvant (chemo)radiotherapy plus total mesorectal excision between 2004 and 2015 were included in the study. LLND was performed when pretreatment imaging documented enlarged LLNs (7 mm or greater in size). Localization of nodal metastases and long-term outcomes were analysed. Kaplan-Meier analysis was used to compare the survival of patients with ypN0 disease with that of patients with mesorectal ypN+/LLN- status and patients with positive LLNs. The Cox proportional hazards model was used to evaluate predictors of disease-free survival (DFS) and local recurrence.. A total of 613 patients were included in the study; LLND was performed in 212 patients (34·6 per cent) and 57 (9·3 per cent) had LLN metastasis. Patients with LLN metastasis had improved DFS and local recurrence cumulative incidence rates compared with patients with mesorectal ypN2+/LLN- disease (DFS:. LLN metastasis is not an independent predictor of local recurrence or survival. Survival of patients presenting with LLN metastasis after (chemo)radiotherapy was intermediate between that of patients with ypN0 status and those with mesorectal ypN2 positivity.. No existen en la literatura grandes estudios dirigidos a investigar la importancia pronóstica de las metástasis en los ganglios linfáticos laterales (. Se realizó una LLND en 212 (34,6%) pacientes, y 57 (9,3%) pacientes presentaban metástasis en los LLN. Los pacientes con metástasis en los LLN presentaron mejores curvas de incidencia acumulada de recidiva local y de supervivencia libre de enfermedad en comparación con los pacientes con ganglios mesorrectales ypN2 positivos/LLN negativos (respectivamente,. Las metástasis en los LLN no es un factor predictivo independiente de recidiva local o supervivencia. Los pacientes que presentaron metástasis en los LLN después de (quimio)radioterapia mostraron características de supervivencia intermedias entre ypN0 y pacientes con ganglios mesorrectales ypN2 positivos.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Disease-Free Survival; Female; Fluorouracil; Humans; Incidence; Kaplan-Meier Estimate; Leucovorin; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasm, Residual; Organoplatinum Compounds; Proctectomy; Prognosis; Rectal Neoplasms; Rectum; Retrospective Studies

Vulvar metastasis of colorectal cancer (CRC) and acquired resistance to cetuximab is a very rare phenomenon. To our knowledge, few cases have been reported in the English literatures.. A 55-year-old woman was diagnosed as adenocarcinoma of the rectum and the primary tumor was detected to be Kirsten-RAS (KRAS) wild type.. The patient was diagnosed with rectal adenocarcinoma by colonoscopy. Positron emission tomography/computed tomography (PET-CT) revealed multiple lymph node and bone metastases.. The patient received a first-line course of palliative chemotherapy with FOLFOX combined with cetuximab.. After an initial response, acquired resistance to cetuximab occurred and vulvar metastasis was established by a second biopsy. Further molecular analysis showed that the KRAS mutation was detected in plasma samples and tumor tissues.. Vulvar metastasis from CRC is relatively rare and indicates a poor prognosis. Routine physical examinations of cutaneous and subcutaneous may facilitate early detection of metastases and timely intervention of medical technology. Moreover, combining serial tumor biopsy, liquid biopsy, and radiologic imaging could help to define mechanisms of drug resistance and to guide selection of therapeutic strategies.

Topics: Adenocarcinoma; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Cetuximab; Drug Resistance, Neoplasm; Fatal Outcome; Female; Fluorouracil; Humans; Leucovorin; Middle Aged; Mutation; Organoplatinum Compounds; Proto-Oncogene Proteins p21(ras); Rectal Neoplasms; Vulvar Neoplasms

We report 2 cases of advanced colorectal cancer achieving complete response by FOLFOXIRI plus bevacizumab. Case 1 was a 65-year-old male diagnosed with descending colon cancer with multiple liver metastases. Six courses of FOLFOXIRI plus bevacizumab were administered after laparoscopic-assisted left hemicolectomy. Ten partial hepatectomies and 1 radiofrequency ablation were performed as the liver metastases resolved. A pathological complete response was confirmed. Adjuvant chemotherapy was not administered, and recurrence-free survival was 21 months after hepatectomy. Case 2 was a 77-yearold male diagnosed with rectal cancer invading the pelvic wall and sacral foramen with bilateral lateral lymph node metastasis. Additionally, there was a cancer embolism in the right internal iliac vein. Six courses of FOLFOXIRI plus bevacizumab were administered, and the cancer tissue was absent on subsequent CT and MRI. The cancer was scarred by colonoscopy, and the biopsy showed no malignant cells. Six courses of FOLFIRI plus panitumumab were administered as second-line chemotherapy, and the patient survived without any recurrence after 12 months from initiation of chemotherapy.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colonic Neoplasms; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Neoplasm Recurrence, Local; Organoplatinum Compounds; Rectal Neoplasms

With the advancement ofchemotherapy against colorectal cancer, clinical complete responses(cCR)are more frequently observed. We report a case oflocally advanced rectal cancer with maintained long-term cCR after chemotherapy alone. Detailed examinations ofa man in his 60s revealed that he had poorly controlled diabetes mellitus, with elevated serum CEA and CA19-9 levels. Colonoscopy revealed rectal cancer(Rba). Besides the prostate invasion observed in the CT scan, intestinal obstruction was caused by a tumor that required surgical removal. However, the tumor was unresectable due to prostate and pelvic wall metastases; therefore, only sigmoid colostomy was performed. After 6 courses of mFOLFOX6, the tumor shrunk, and prostate invasion reduced as confirmed by the CT scan. Chemotherapy was switched to sLV/5FU2 due to the occurrence of peripheral neuropathy. No tumor was found after 20 courses of treatment, and cCR was achieved after 58 courses ofcontinuous and consecutive treatment. Throughout the treatment, radical resection was proposed to the patient; however, the surgery was not performed because of his lifestyle, ie, heavy smoking, which resulted in poor blood sugar control. The patient appears to be tumor free for 7 years after the initiation of chemotherapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Colostomy; Fluorouracil; Humans; Leucovorin; Male; Rectal Neoplasms

Neoadjuvant chemoradiation therapy is part of the standard treatment of locally advanced rectal cancer (LARC). Although various options for modifying preoperative radiotherapy protocols have been researched and proposed, there is still no consensus as to the most appropriate dose regimen of neoadjuvant therapy for this disease.. To evaluate the effects of relatively low-dose radiation regimens on tumor regression and clinical outcomes in rectal cancer patients treated with neoadjuvant CRT followed by mesorectal excision.. We retrospectively analyzed patients with LARC who underwent neoadjuvant concurrent chemoradiation (CCRT) in our hospital from June 2010 to December 2015. A total of 259 consecutive patients were enrolled, receiving 42 to 44 Gy (RLD, n = 31), 46 Gy (SD1, n = 69), or 50 Gy (SD2, n = 159) of CRT, combined with either capecitabine/oxaliplatin or capecitabine only or mFOLFOX6, followed by total mesorectal excision. A 1:4 propensity score matching was employed, and all patients in the RLD group were matched with 124 patients in the SD2 group. Rates of pCR, 3-year local/regional recurrence (LRR), overall survival (OS), and disease-free survival (DFS) in the RLD group were all not significantly different (0.313 for pCR; 0.884 for LRR; and 0.762 for OS; 0.101 for DFS) from those in SD1 and SD2 groups. The RLD group showed a lower incidence of grade 3 to 4 hematologic toxicity than SD2 group (0.019). A propensity score analysis demonstrated no significant differences in the pCR rates and 3-year outcomes between the RLD and SD2 group.. Relatively low-dose regimen (≤44 Gy) of neoadjuvant CRT combined with standard concurrent chemotherapy appears to be both safe and effective in Chinese patients with LARC. Further testing by prospective randomized trials is needed.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Disease-Free Survival; Dose-Response Relationship, Radiation; Feasibility Studies; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Organoplatinum Compounds; Proctectomy; Propensity Score; Radiation Injuries; Rectal Neoplasms; Rectum; Retrospective Studies

This study aimed to investigate clinicopathological responses and oncological outcome in patients receiving short- or long-course chemoradiotherapy (CRT) and to assess the predictive factor for recurrence in each treatment.. A total of 118 rectal cancer patients receiving preoperative CRT were enrolled. Clinicopathological responses and oncological outcome in patients receiving short- or long-course CRT were investigated.. Despite there being no significant differences in the prognosis of disease-free survival (DFS) based on TNM stage classification in patients receiving long-course CRT, patients with advanced stage demonstrated poor DFS after short-course CRT. The presence of lymph node metastasis was a predictor of poor DFS in short-course CRT, whereas poor pathological response was a predictor of recurrence in long-course CRT.. Distinct predictors of recurrence depending on the CRT course might be needed to discriminate candidates from rectal cancer patients receiving preoperative CRT who might benefit from more intensive adjuvant therapy after surgery.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Chemotherapy, Adjuvant; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Rectal Neoplasms; Retrospective Studies; Survival Rate; Tegafur; Uracil

The role of adjuvant chemotherapy after preoperative chemoradiation therapy (CRT) and curative surgery in rectal cancer has yet to be definitely determined. We performed a retrospective and multicenter study to evaluate whether adjuvant chemotherapy (AC) could reduce recurrence and improve survival in locally advanced rectal cancer.. We analyzed data from 8 tertiary institutions for 1442 patients with rectal cancer who underwent preoperative CRT and total mesorectal excision. Patients were classified into 2 groups: the AC group (patients who received chemotherapy after surgery) and the observation group (those who did not receive chemotherapy after surgery). Propensity-score matching was used to assess the exact role of AC. The AC group was then subdivided to investigate the impact of adding oxaliplatin to 5-fluorouracil (5-FU). Group 1 was treated with 5-FU/folinic acid or capecitabine without oxaliplatin, and group 2 received 5-FU/folinic acid or capecitabine with oxaliplatin.. The 3-year relapse-free survival rates in the AC and observation groups were 85.9% and 84.3%, respectively (P = .532). The 3-year overall survival rates in the AC and observation groups were 94.9% and 89.9%, respectively (P = .123). The rates of locoregional recurrence (2.2% vs 3.2%, P = .294) and distant metastasis (12.4% vs 12.9%, P = .927) at 3 years were not significantly different between the two groups. The 3-year relapse-free survival rates of group 1 and group 2 were 71.5% and 74.8%, respectively (P = .426). The 3-year overall survival rates of group 1 and group 2 were 89.9% and 96.5%, respectively (P = .102).. This multicenter study found insufficient evidence to support the use of 5-FU-based AC after preoperative CRT and curative surgery in rectal cancer.

Topics: Aged; Capecitabine; Chemoradiotherapy; Chemotherapy, Adjuvant; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Oxaliplatin; Propensity Score; Rectal Neoplasms; Recurrence; Retrospective Studies; Treatment Outcome

Preoperative radio(chemo)therapy in rectal cancer may irreversibly damage pelvic bone marrow (PBM) and impair the tolerance of subsequent chemotherapy. The aim of the study was to assess the relationship between the irradiated volume of PBM and the toxicity of subsequent 5-fluorouracil, oxaliplatin, leucovorin (FOLFOX-4) in rectal cancer. We included consecutive rectal cancer patients who received FOLFOX-4 postoperatively or due to cancer relapse. The PBM was divided into iliac (IM), lumbosacral (LSM), and lower pelvic (LPM) marrow. We assessed mean dose, and percentage of volume receiving 10%-90% (V10%-V90%) of the prescribed dose for PBM, IM, LSM, and LPM. Generalized linear model for repeated measures (GLM) was used to test an influence of dose-volumes distribution on toxicities grade 2 or higher (TOX2) and grade 3 or higher (TOX3). The two-sided t-test was used to evaluate the difference in mean dose, mean V20%, and mean V40% between patients who experienced TOX2 or TOX3 and those who did not. 39 patients met eligibility criteria. Because of the low occurrence of TOX3 (n=3), related analyses were abandoned. We found no influence of dose-volume distribution on TOX2 in GLM and no significant differences in mean dose, mean V20%, and mean V40% for PBM, IBM, LSM, and LPM between patients who experienced TOX2 and those who did not. To conclude, no relationship between doses received by PBM in preoperative radio(chemo)therapy in rectal cancer and hematological tolerance of subsequent FOLFOX-4 chemotherapy was found.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Chemoradiotherapy; Fluorouracil; Humans; Leucovorin; Neoplasm Recurrence, Local; Organoplatinum Compounds; Pelvic Bones; Rectal Neoplasms

Pathologic complete response (pCR) is associated with better prognosis and guides management for patients with advanced rectal cancer. Response rates vary between series for unclear reasons. We examine whether the thoroughness of pathologic assessment explains differences in pCR rates.. We retrospectively reviewed pathology reports from patients with stage II/III rectal cancer who underwent chemoradiation and resection in a prospective, multicenter trial. We utilized a novel measure for the thoroughness of pathologic assessment by dividing residual tumor size by the number of cassettes evaluated (tumor size to cassette ratio, TSCR), and evaluated whether TSCR is associated with pCR. We validated our findings using a separate cohort.. From the trial cohort, 71 of 247 (29%) patients achieved pCR. The pCR rate ranged from 0 to 45% and mean TSCR ranged 0.29 to 0.87 across 12 institutions. Within each institution, a lower TSCR was associated with pCR, demonstrating a higher degree of thoroughness used for tumors that achieved pCR. Moreover, across all samples, low TSCR was independently associated with pCR on multivariable analysis. This finding was corroborated in a separate cohort of 201 tumors evaluated by five pathologists; each pathologist had a lower mean TSCR for pCR calls compared with non-pCR calls. However, the mean TSCR for an institution was not associated with its overall pCR rate.. Pathologists assess rectal cancers that have responded significantly to neoadjuvant therapy more thoroughly. Thoroughness does not appear to explain differences in pCR rates between institutions. Our results suggest pCR is not a sampling artifact.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Cohort Studies; Fluorouracil; Humans; Leucovorin; Mesentery; Multivariate Analysis; Neoadjuvant Therapy; Neoplasm Staging; Neoplasm, Residual; Organoplatinum Compounds; Pathologists; Practice Patterns, Physicians'; Proctectomy; Prognosis; Prospective Studies; Rectal Neoplasms; Retrospective Studies; Tumor Burden

To evaluate the pattern of tumor relapse of pathological complete response (pCR) patients with locally advanced rectal cancer (LARC) following neoadjuvant chemoradiotherapy (nCRT) and total mesorectal excision (TME), and to identify predictive factors of distant metastasis in pCR patients after nCRT.. This was a retrospective analysis of 118 LARC patients who achieved a pCR following nCRT and TME from 2008 to 2015. Clinicopathological and therapeutic parameters were evaluated as possible predictors of distant metastasis-free survival (DMFS), and COX regression analysis was performed.. After a median follow-up of 57 months, the 5-year overall and disease-free survival rates were 94.7% and 88.1%, respectively. Overall, 6 patients (5.1%) died, no local recurrence occurred, 13 patients (11%) developed distant metastases, including lung (n = 5), liver (n = 2), bone (n = 3), lung and brain (n = 1), peritoneal (n = 1), and spleen (n = 1) metastasis. On univariate analysis, tumor distance from the anal verge (HR = 0.706, P = 0.039), acellular mucin pools (HR = 6.687, P = 0.002), and MUC1 expression (HR = 8.280, P < 0.001) were independently associated with DMFS. COX regression demonstrated that MUC1 expression (HR = 3.812, P = 0.041) remained to be an independent predictor of DMFS in pCR patients.. Distant metastasis still remained a major concern in pCR patients following nCRT and TME. Tumor distance from the anal verge, acellular mucin pools, and MUC1 expression were associated with distant metastasis in patients with pCR. MUC1 staining remained to be an independent risk factor for DMFS. Such information could facilitate treatment decision in these patients, such as adjuvant chemotherapy and follow-up.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Brain Neoplasms; Capecitabine; Chemoradiotherapy; Chemotherapy, Adjuvant; Disease-Free Survival; Female; Fluorouracil; Humans; Incidence; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Mesentery; Middle Aged; Mucin-1; Mucins; Neoadjuvant Therapy; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms; Proctectomy; Proportional Hazards Models; Rectal Neoplasms; Remission Induction; Retrospective Studies; Splenic Neoplasms

With advances in systemic therapies, the role of primary tumor resection may be of increased importance in patients with metastatic rectal cancer. The role of combining pelvic radiotherapy with surgical resection in the metastatic setting is unknown. We utilized the National Cancer Database to examine outcomes in patients with metastatic rectal adenocarcinoma with primary tumor resection with and without pelvic radiotherapy.. We queried the National Cancer Database from 2004 to 2014 for patients with stage IV rectal adenocarcinoma receiving chemotherapy. We identified 4051 patients in that group that had primary tumor resection. Patients were then stratified by receipt of pelvic radiotherapy (yes = 1882; no = 2169) Univariable and multivariable analyses identified characteristics predictive of overall survival. Propensity-adjusted Cox proportional hazard ratios for survival were used to account for indication bias.. The median patient age was 63 years (range, 18-90 years) with a median follow-up of 32.3 months (range, 3.02-151.29 months). There were proportionately more patients with T3/T4 disease or N1 disease in the surgery plus radiotherapy arm. The median survival was 46.3 months versus 35.3 months in favor of addition of radiotherapy (P < .001). The 2- and 5-year overall survival was 68.4% and 24.8% for surgical resection alone compared with 77.2% and 39.6% for surgery + radiotherapy. On propensity-adjusted multivariable analysis, radiotherapy was associated with a statistically significant reduction in risk of death (hazard ratio, 0.722; 95% confidence interval, 0.0665-0.784).. This analysis indicates that in patients with metastatic rectal adenocarcinoma receiving chemotherapy, pelvic radiotherapy in addition to primary tumor resection may be of significant benefit.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Databases, Factual; Datasets as Topic; Female; Fluorouracil; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Proctectomy; Proportional Hazards Models; Rectal Neoplasms; Rectum; Time Factors; Treatment Outcome; Young Adult

We report a case of locally advanced rectal cancer presenting with perforation that was successfully resected after preoperative chemotherapy. A 66-year-old woman visited our emergency room complaining of lower abdominal pain. Abdominal CT showed a rectal tumor with fluid collection and free air in the pelvis. The patient was diagnosed with panperitonitis secondary to cancerous perforation and underwent sigmoid colostomy. A biopsy specimen of the rectal tumor showed well-differentiated tubular adenocarcinoma and wild-type RAS. After 8 courses of mFOLFOX6 plus panitumumab, the tumor shrank remarkably, and radical surgery(low anterior resection with D3 lymph node dissection)was performed. Microscopic examination of the resected specimen showed that almost half of the tumor cells were replaced by histiocytes and necrotic tissue. Preoperative chemotherapy with panitumumab may be an effective treatment for RAS wild-type locally advanced colon cancer, even if the primary tumor develops perforation.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Leucovorin; Organoplatinum Compounds; Panitumumab; Rectal Neoplasms

Topics: Cetuximab; Fluorouracil; Humans; Leucovorin; Oxaliplatin; Rectal Neoplasms

Initial treatment with either neoadjuvant chemoradiation (CRT) or induction FOLFOX (5-Fluorouracil, leucovorin, and oxaliplatin) chemotherapy followed by CRT is considered standard treatment for locally advanced rectal cancer. We compared patient-reported outcomes (PRO) during CRT in patients who had received induction chemotherapy versus those who did not.. We reviewed records of patients with locally advanced rectal cancer who were treated with CRT between September 2009 and October 2014, and who had completed ≥ 4 PRO assessments during treatment. Clinician- and patient-reported toxicities were collected each week during treatment. We fit binomial generalized linear models to maximum toxicity scores across all patients' visits.. Of 123 patients with ≥ 4 PRO assessments, 87 (71%) patients reported a clinically meaningful PRO score of 3 or higher for diarrhea, and 91 (74%) patients reported a PRO score of ≥ 3 for urgency, during 1 or more weeks of treatment, corresponding to 'very frequent' or worse. Of 116 patients who had also completed ≥ 4 clinician-reported assessments for descriptive analysis, clinically significant diarrhea (Common Terminology Criteria for Adverse Events grade ≥ 2) was reported in 9% of patients, and grade 2 proctitis and cystitis were reported in 20% and 4%, respectively. Eighty-four (68%) patients had undergone induction chemotherapy prior to CRT. Patients who received induction chemotherapy had 68% lower odds of experiencing significant urgency (odds ratio [OR], 0.32; 95% confidence interval [CI], 0.11-0.95; P = .04), 76% lower odds of bleeding (OR, 0.24; 95% CI, 0.1-0.62; P < .01), and 75% lower odds of tenesmus (OR, 0.25; 95% CI, 0.11-0.6; P < .01) versus those treated with upfront CRT.. Based on PROs, a high proportion of patients experienced clinically significant symptoms during pelvic CRT, with diarrhea and urgency being most commonly reported. This appears to be under-reported on clinician-reported assessments. Delivery of induction chemotherapy was associated with lower odds of experiencing urgency, bleeding, and tenesmus on PROs during subsequent CRT, with no significant impact on diarrhea and rectal pain.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Diarrhea; Female; Fluorouracil; Hemorrhage; Humans; Induction Chemotherapy; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Patient Reported Outcome Measures; Proctectomy; Radiotherapy, Intensity-Modulated; Rectal Neoplasms; Rectum; Retrospective Studies; Urination Disorders; Young Adult

A 60-year-old woman underwent intersphincteric resection for lower rectal cancer in 2016. The pathological stage was pT3N1M0, stage Ⅲa and the cancer was curatively resected. Local recurrence was detected 6 months after the surgery. The patient received chemotherapy of 4 courses of FOLFOXIRI plus bevacizumab(Bev). A Grade 4 adverse event(febrile neutropenia) occurred but the treatment was continued after a dose reduction to 80%. The size of the tumor decreased significantly after chemotherapy and posterior pelvic exenteration with sacral resection was performed. Pathological analysis revealed a positive radial margin but there were no remarkable complications after surgery and no obvious recurrence during the 9 months after the operation. Therefore, we concluded that FOLFOXIRI plus Bev chemotherapy is a manageable and useful treatment for locally recurrent rectal cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Female; Fluorouracil; Humans; Leucovorin; Middle Aged; Neoplasm Recurrence, Local; Organoplatinum Compounds; Rectal Neoplasms

Recent studies have shown a marked increase of AT-rich interactive domain 3A (ARID3A) in colon cancer tissue compared to normal colon mucosa. However, the role of ARID3A has not yet been determined in rectal cancer. We, therefore, investigated the clinical relevance of ARID3A expression in patients with residual rectal cancer after neoadjuvant chemoradiotherapy (NACRT).. One hundred thirty-four patients who underwent surgical resection for residual rectal cancer after NACRT were analyzed. ARID3A expression was evaluated using immunohistochemistry on whole-tissue sections. KRAS exon 2 (codons 12 and 13) and BRAF V600E mutation status were determined using polymerase chain reaction.. ARID3A positivity was found in 91 cases (64.5%), and it correlated with absence of perineural invasion (p=0.031), longer disease-free survival (DFS) (p=0.048) and cancer-specific survival (CSS) (p=0.006). However, ARID3A positivity was not correlated with KRAS (p=0.231) or BRAF mutation status (p=0.577). In multivariate analysis, ARID3A positivity was independently associated with a favorable CSS (p=0.035), but not DFS (p=0.051).. ARID3A positivity can predict favorable prognosis in patients with residual rectal cancer after NACRT.

Topics: Adult; Aged; Aged, 80 and over; Chemoradiotherapy, Adjuvant; Disease-Free Survival; DNA-Binding Proteins; Female; Fluorouracil; Gene Expression Regulation, Neoplastic; Humans; Leucovorin; Male; Middle Aged; Mutation; Neoadjuvant Therapy; Neoplasm, Residual; Prognosis; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras); Rectal Neoplasms; Retrospective Studies; Transcription Factors; Treatment Outcome; Up-Regulation

The patient was a 65-year-old man. His complaints included bloody stools and pain on urination. A detailed examination suggested vesical wall invasion, leading to a diagnosis of rectosigmoid cancer(cT4b, N+, M0). For R0 surgery, total cystectomy was considered necessary. To maintain vesical function, tumor-reducing chemotherapy was selected. After colostomy for the sigmoid colon, 4 courses of mFOLFOX6 plus bevacizumab therapy were administered. There was a marked reduction in the tumor size; therefore, 3 courses of mFOLFOX6 plus panitumumab therapy were administered as preoperative chemotherapy before resection. Partial response(PR)was achieved, and there was no urinary bladder infiltration. Therefore, surgery was performed. There was no tumor invasion to any other organ. High anterior rectal resection was performed. The pathological diagnosis also confirmed the efficacy of chemotherapy. We report about a patient in whom extended surgery could be avoided by administering chemotherapy for advanced rectosigmoid cancer with urinary bladder invasion.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Leucovorin; Male; Neoadjuvant Therapy; Neoplasm Invasiveness; Organoplatinum Compounds; Rectal Neoplasms; Sigmoid Neoplasms; Urinary Bladder

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Capecitabine; Carcinoembryonic Antigen; Chemoradiotherapy; Female; Fluorouracil; Follow-Up Studies; GPI-Linked Proteins; Humans; Leucovorin; Lymphocytes; Male; Middle Aged; Neoadjuvant Therapy; Neutrophils; Oxaliplatin; Prognosis; Rectal Neoplasms; Retrospective Studies; ROC Curve; Survival Rate; Young Adult

Treatment of locally advanced rectal (LARC) cancer involves chemoradiation, surgery, and chemotherapy. The concept of total neoadjuvant therapy (TNT), in which chemoradiation and chemotherapy are administered prior to surgery, has been developed to optimize delivery of effective systemic therapy aimed at micrometastases.. To compare the traditional approach of preoperative chemoradiation (chemoRT) followed by postoperative adjuvant chemotherapy with the more recent TNT approach for LARC.. A retrospective cohort analysis using Memorial Sloan Kettering Cancer Center (MSK) records from 2009 to 2015 was carried out. A total of 811 patients who presented with LARC (T3/4 or node-positive) were identified.. Of the 811 patients, 320 received chemoRT with planned adjuvant chemotherapy and 308 received TNT (induction fluorouracil- and oxaliplatin-based chemotherapy followed by chemoRT).. Treatment and outcome data for the 2 cohorts were compared. Dosing and completion of prescribed chemotherapy were assessed on the subset of patients who received all therapy at MSK.. Of the 628 patients overall, 373 (59%) were men and 255 (41%) were women, with a mean (SD) age of 56.7 (12.9) years. Of the 308 patients in the TNT cohort, 181 (49%) were men and 127 (49%) were women. Of the 320 patients in the chemoRT with planned adjuvant chemotherapy cohort, 192 (60%) were men and 128 (40%) were women. Patients in the TNT cohort received greater percentages of the planned oxaliplatin and fluorouracil prescribed dose than those in the chemoRT with planned adjuvant chemotherapy cohort. The complete response (CR) rate, including both pathologic CR (pCR) in those who underwent surgery and sustained clinical CR (cCR) for at least 12 months posttreatment in those who did not undergo surgery, was 36% in the TNT cohort compared with 21% in the chemoRT with planned adjuvant chemotherapy cohort.. Our findings provide additional support for the National Comprehensive Cancer Network (NCCN) guidelines that categorize TNT as a viable treatment strategy for rectal cancer. Our data suggest that TNT facilitates delivery of planned systemic therapy. Long-term follow-up will determine if this finding translates into improved survival. In addition, given its high CR rate, TNT may facilitate nonoperative treatment strategies aimed at organ preservation.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemoradiotherapy; Chemotherapy, Adjuvant; Combined Modality Therapy; Dose Fractionation, Radiation; Female; Fluorouracil; Humans; Ileostomy; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Invasiveness; Neoplasm Micrometastasis; Organoplatinum Compounds; Oxaliplatin; Postoperative Care; Preoperative Care; Proctectomy; Radiotherapy, Conformal; Radiotherapy, Intensity-Modulated; Rectal Neoplasms; Remission Induction; Retrospective Studies

Comorbidity has a detrimental effect on cancer survival, however, it is difficult to disentangle its direct effect from its influence on treatment choice. In this study we assessed the effect of comorbidity on survival in patients who received standard treatment for resected stage II and III colorectal cancer (CRC).. In total, 230 CRC patients, 68 rectal (29.6%) and 162 colon cancer (70.4%) treated with surgical resection and neoadjuvant/adjuvant chemotherapy from December 2002 to December 2009 at Humanitas Cancer Center were retrospectively reviewed. The key independent variable was the Charlson Comorbidity Index (CCI) score, measured as a continuous variable. The differences between groups for categorical data were tested using the χ. Median follow-up was 113 (range, 8.2-145.0) months. Median age was 63 (range, 37-78) years. In univariate analysis CCI score was significantly associated with poorer disease-free survival (hazard ratio [HR], 1.65; 95% confidence interval [CI], 1.52-1.80; P < .001), and overall survival (OS; HR, 1.55; 95% CI, 1.41-1.71; P < .001). Factors associated with poorer outcome also included (stage III vs. stage II, P < .029) and age (age >70 vs. ≤70 years, P < .001). After adjusting for these factors, a significant negative prognostic role of CCI score was still observed (adjusted HR for OS, 1.59; 95% CI, 1.43-1.76; P < .001).. Among CRC patients who underwent surgical resection and chemotherapy, a higher CCI score was associated with poorer outcome and might predict long-term survival.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemoradiotherapy; Chemotherapy, Adjuvant; Colon; Colonic Neoplasms; Comorbidity; Deoxycytidine; Disease-Free Survival; Female; Fluorouracil; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Oxaloacetates; Progression-Free Survival; Rectal Neoplasms; Rectum; Retrospective Studies

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Clinical Trials, Phase III as Topic; Colonic Neoplasms; Disease-Free Survival; Drug Administration Schedule; Equivalence Trials as Topic; Fluorouracil; Humans; Leucovorin; Neoplasm Staging; Organoplatinum Compounds; Rectal Neoplasms; Treatment Outcome

The NCCN Guidelines for Rectal Cancer are now more closely aligned with those for colon cancer. A new MRI-based definition of the rectum has been included and the use of MRI in staging has been elevated in importance. There is a new emphasis on neoadjuvant therapy, especially the concurrent use of chemotherapy and radiotherapy. One of the biggest changes is more acceptance of an observational approach-"watch and wait, nonoperative management"-for select patients experiencing a complete clinical response with no evidence of residual disease after neoadjuvant therapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Disease-Free Survival; Fluorouracil; Humans; Leucovorin; Medical Oncology; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Practice Guidelines as Topic; Proctectomy; Rectal Neoplasms; Rectum; Societies, Medical; United States; Watchful Waiting

Studies have suggested that the use of neoadjuvant chemoradiation results in a lower lymph nodes yield in rectal cancer patients.. To evaluate factors associated with less than 12 lymph nodes harvested on patients with rectal cancer treated with preoperative chemoradiotherapy followed by total mesorectal excision.. This was a cohort/retrospective single cancer center study. Low and mid locally advanced rectal cancer or T2N0 under risk of sphincter resection underwent chemoradiotherapy followed by total mesorectal excision with curative intent. Chemotherapy consisted of 5-FU and leucovorin IV. Total dose of pelvic radiation was 5040 Gys. All patients were staged and restaged by digital rectal examination, proctoscopy, colonoscopy, CT of abdomen and chest, and MRI of the pelvis. Patients were stratified in two groups: ≥12 and < 12 L N retrieved. The possible factors affecting number of LN were analyzed.. 95 patients met the inclusion criteria. Mean LN harvest was 23.2 (3-67). 81 patients (85%) had ≥12 L N. Gender, age, tumor size, tumor stage, tumor location, length of specimen, presence of LN involvement, type of surgery, and surgical access showed no association with number of LN retrieved. Only pathological complete response showed a statistically significant association with <12 L N on univariate (p = 0.004) and multivariate analyses (p = 0.002).. Data were collected retrospectively. The number of patients disparity between the two groups.. Complete pathologic response is associated with <12 L N harvested. Thus, the number of lymph nodes should not be used as a surrogate for oncologic adequacy of resection in patients with pathologic complete response.

Topics: Adult; Aged; Antineoplastic Agents; Biopsy; Chemoradiotherapy; Female; Humans; Leucovorin; Lymph Nodes; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Pelvis; Proctocolectomy, Restorative; Rectal Neoplasms; Rectum; Retrospective Studies; Treatment Outcome

A 50s man receiving dialysis for chronic kidney disease due to IgA nephropathy underwent laparoscopic reversal via Hartmann 's procedure for rectal cancer and multiple liver metastases, followed by chemotherapy for the liver metastases. Following a single course of mFOLFOX therapy, bevacizumab was administered for 8 courses, resulting in tumor shrinkage and a decrease in tumor marker levels. The initial doses were 60mg/m2 oxaliplatin and 280(bolus injection)and 1,680mg/m2 (continuous infusion)of 5-FU. Subsequently, these doses were adjusted to be administered every 3 weeks. No serious adverse events other than neutropenia(Grade3 ), anorexia(Grade1 ), and hiccups(Grade1)were noted.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Fluorouracil; Glomerulonephritis, IGA; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Rectal Neoplasms; Renal Dialysis

A 50-year old male patient chose to have elective surgery for obstructive rectal cancer. Before undergoing surgery, he had a self-expandable metallic stent (SEMS) placed to relieve a colonic obstruction. He was discharged from our hospital after the elective surgery without surgical complications. In our outpatient clinic, he was prescribed UFT/LV for adjuvant chemotherapy. Eight months after surgery, he came back to the hospital complaining of abdominal distension, abdominal pain and constipation. A diagnosis of local recurrence of rectal cancer, peritoneal metastasis and metastatic liver cancer was confirmed. He was admitted to have the bowel obstruction relieved by having a SEMS placed. The procedure was successful in relieving the bowel obstruction and the patient began FOLFIRI plus bevacizumab as chemotherapy. Through this case, we were able to see that SEMS placement can circumvent emergency surgery and prevent the formation of a stoma by relieving a colonic obstruction. A SEMS placement can also lead to positive benefits such as faster treatment and therapy for palliative cases.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Fluorouracil; Humans; Intestinal Obstruction; Leucovorin; Male; Middle Aged; Rectal Neoplasms; Recurrence; Self Expandable Metallic Stents; Sigmoid Neoplasms

Therapy-related myelodysplasticsyndrome(t-MDS)has been reported to occur after treatment with cytotoxic agents and radiation. Here, we report a case of t-MDS following oxaliplatin(L-OHP)exposure, which was successfully treated with azacitidine(AZA). A 71-year-old man was referred to our department because of pancytopenia. He had been diagnosed with rectal cancer(cT4aNXM0, stage II B-III C, RAS gene status wild-type)3 years ago and had received 8 courses of capecitabine(CAP)and L-OHP(XELOX regimen), followed by 48 courses of CAP and bevacizumab. Before referral, recurrence of rectal cancer was detected using CT after the last course of chemotherapy. A bone marrow examination revealed multilineage dysplasia and 9.0%myeloblasts. Cytogenetic analysis disclosed a chromosome 7 abnormality. The diagnosis of t- MDS was made and treatment with AZA was initiated. Subsequently, temporary but significant hematological improvements were observed, which enabled the patient to receive additional palliative radiation therapy against the locally relapsed rectal cancer. AZA might be useful in t-MDS because of its efficacy and low toxicity.

Topics: Aged; Antimetabolites, Antineoplastic; Azacitidine; Combined Modality Therapy; Fatal Outcome; Humans; Leucovorin; Male; Myelodysplastic Syndromes; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms

Topics: Anal Canal; Antineoplastic Combined Chemotherapy Protocols; Arterioles; Collagen; Dilatation, Pathologic; Dose-Response Relationship, Radiation; Edema; Endothelium, Vascular; Fibroblasts; Fluorouracil; Humans; Leucovorin; Lymphatic Vessels; Muscle, Smooth; Myofibrils; Organoplatinum Compounds; Perineum; Radiotherapy, Adjuvant; Rectal Neoplasms; Rectum; Tunica Media

A 56-year-old woman was diagnosed with rectal cancer and liver metastases(Stage IV), and underwent low anterior resection and laparoscopic partial hepatectomy. The patient received adjuvant chemotherapy(mFOLFOX6 for 24 weeks), but developed multiple lung metastases 11 months later. Before undergoing a pulmonary resection, the patient presented with acute small bowel obstruction. Abdominal computed tomography showed small bowel stenosis due to a tumor, and we suspected peritoneal metastases from the rectal tumor. We performed partial resection of the small intestine, and histopathological examination revealed a primary small bowel tumor. The patient was discharged to her home without complications, and later underwent pulmonary resections for bilateral lung metastases. We usually suspect that small bowel obstruction is due to peritoneal metastases in patients with advanced colorectal tumors, but must consider the rare possibility of a separate primary small bowel tumor, especially in patients with a solitary lesion. We report a rare primary small bowel tumor after FOLFOX treatment in a patient with Stage IV rectal cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Intestinal Neoplasms; Intestine, Small; Leucovorin; Liver Neoplasms; Lung Neoplasms; Middle Aged; Neoplasms, Multiple Primary; Organoplatinum Compounds; Rectal Neoplasms

Systemic inflammatory response, as measured by C-reactive protein (CRP), is associated with prognosis in various types of human malignancies. However, to the best of our knowledge, the clinical significance of CRP in patients with locally advanced rectal cancer that undergo preoperative chemoradiation has not been investigated in detail. This retrospective study validates CRP as a potential predictive marker for survival outcomes in rectal cancer patients.. In this study, we enrolled 125 patients that received total mesorectal excision after preoperative chemoradiation for rectal cancer between January 2003 and December 2010. We investigated the association between preoperative CRP and clinicopathological characteristics and assessed the prognostic value of CRP.. The median follow-up was 41 months. Elevated CRP showed significant correlation with high histological grade (P = 0.009) and cancer recurrence (P = 0.027). The 5-year disease-free survival and cancer-specific survival were significantly lower in the elevated CRP group (P = 0.001). Moreover, CRP was the strongest predictive factor for cancer-specific survival in multivariate analysis (P = 0.001). In the subgroup analysis, elevated CRP was a significant prognostic factor in patients with node-positive disease (P = 0.025) and was associated with poorer tumor regression (TRG4-5; P = 0.011).. The results of our study suggest that preoperative CRP level shows prognostic significance in rectal cancer patients that have undergone chemoradiation. Therefore, preoperative CRP may help clinicians to identify patients that need additional therapy to reduce systemic failure.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Body Mass Index; C-Reactive Protein; Capecitabine; Chemoradiotherapy, Adjuvant; Digestive System Surgical Procedures; Disease-Free Survival; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Grading; Neoplasm Staging; Preoperative Period; Radiotherapy Dosage; Rectal Neoplasms; Survival Rate

In order to reduce the frequency and the severity of oxaliplatin-related sensory-neuropathy and preserve antitumor efficacy, we performed alternating 4 mFOLFOX6 and 4 FOLFIRI cycles, in combination with bevacizumab, in patients with metastatic colorectal cancer. The response rate of alternating mFOLFOX6 and FOLFIRI regimens(FIREFOX)plus bevacizumab was 100%. However, during neoadjuvant chemotherapy for colon cancer, we cannot use bevacizumab due to the concern of adverse events, such as bleeding and perforation. Therefore, we used cetuximab in 8 courses of FIREFOX. As a result, the volumes of the rectum cancers and liver metastases decreased. Thereafter, we used bevacizumab in another 8 courses of FIREFOX. A 77- year-old woman suffered from II type rectum cancer, which was localized 7 cm from the anal verge, with multiple liver metastases. We performed 8 courses of FIREFOX plus cetuximab. After observing a decrease in tumor burden, we performed another 8 courses FIREFOX plus bevacizumab. As a result, CEA and CA19-9 decreased to the normal range, and the size of the rectum cancer and liver metastases decreased. She underwent laparoscopic lower anterior and liver resections in the highvolume center. She presently remains alive with no sighs of recurrence, 18 months after resection.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Cetuximab; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Organoplatinum Compounds; Rectal Neoplasms; Treatment Outcome

Patients with locally advanced rectal cancer (LARC) achieving a pathological complete response (pCR) to neoadjuvant treatment usually have a good prognosis, but only accounted for less than 20%.. We report a case of a 25-year-old male with LARC treated with neoadjuvant FOLFOX chemotherapy, and experienced a pCR. The next-generation sequencing analysis revealed the presence of breast cancer gene 2 (BRCA2) somatic mutation and an increased somatic mutational load without microsatellite instability (MSI). To our knowledge, this is the first report of BRCA2 mutant LARC that demonstrated significant benefit from FOLFOX neoadjuvant treatment.. This case indicated an association of BRCA2 mutation with high mutation loads and an excellent response of oxaliplatin-based chemotherapy regimen for LARC. Our findings encourage further studies to analyze BRCA mutations in patients with LARC, especially for those patients unable or unwilling to receive radiotherapy.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; BRCA2 Protein; Fluorouracil; Humans; Leucovorin; Magnetic Resonance Imaging; Male; Mutation; Neoadjuvant Therapy; Organoplatinum Compounds; Rectal Neoplasms; Sequence Analysis, DNA; Treatment Outcome

A 78-year-old man was admitted with diarrhea. Colonoscopy and computed tomography(CT)revealed rectal cancer with multiple liver metastases. Low anterior resection was performed for local control. After the operation, 5 courses of mFOLFOX6 plus bevacizumab chemotherapy were administered as first-line systemic therapy, but CT showed progressive disease with liver metastases. After the first-line systemic therapy, 2 courses of FOLFIRI plus bevacizumab chemotherapy were performed as second-line systemic therapy, but CT also revealed progressive disease with liver metastases. We retrospectively performed comprehensive genomic sequencing with a 415-gene panel and found that the patient had a hypermutation subtype. Interestingly, the panel also revealed that he had mismatch-repair(MMR)deficiency with MSH2 mutation, which is reported as a possible cause of resistance to 5-fluorouracil in colorectal cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Mutation; MutS Homolog 2 Protein; Organoplatinum Compounds; Rectal Neoplasms; Retrospective Studies

Primary cutaneous mucormycosis is an opportunistic fungal infection caused by the order Mucorales, most frequently by the Rhizopus species. Both systemic factors, such as diabetes mellitus or malignancies and local factors disrupting the skin barrier are implicated in development of this entity. The initial manifestation is a red-to-black papule rapidly progressing to a necrotic and painful ulcer. Diagnosis is obtained by identification of fungal forms in a skin biopsy, typically showing branching and non-septate hyphae. The clinical course is highly variable and depends mostly on the fungal invasion of deep tissues. However, an early diagnosis is essential for implementation of prompt and optimal treatment, based upon antifungal therapy and aggressive surgical debridement.

Topics: Adrenal Cortex Hormones; Aged; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Cetuximab; Cross Infection; Debridement; Dermatomycoses; Equipment Contamination; Fluorouracil; Humans; Immunocompromised Host; Leg Ulcer; Leucovorin; Male; Mucormycosis; Organoplatinum Compounds; Rectal Neoplasms; Urinary Catheterization

Preoperative chemoradiotherapy (CRT) using 5-fluorouracil (5-FU)-based chemotherapy is the standard of care for rectal cancer. The effect of additional chemotherapy during the period between the completion of radiotherapy and surgery remains unclear. Predictive factors for CRT may differ between combination chemotherapy with S-1 and with tegafur-uracil/leucovorin (UFT/LV).. The subjects were 54 patients with locally advanced rectal cancer who received preoperative CRT with S-1 or UFT/LV. The pathological tumor response was assessed according to the tumor regression grade (TRG). The expression levels of 18 CRT-related genes were determined using RT-PCR assay.. A pathological response (TRG 1-2) was observed in 23 patients (42.6%). In a multivariate logistic regression analysis for pathological response, the overall expression levels of four genes, HIF1A, MTHFD1, GGH and TYMS, were significant, and the accuracy rate of the predictive model was 83.3%. The effects of the gene expression levels of GGH on the response differed significantly according to the treatment regimen. The total pathological response rate of both high-GGH patients in the S-1 group and low-GGH patients in the UFT/LV group was 58.3%.. Additional treatment with 5-FU-based chemotherapy during the interval between radiotherapy and surgery is not beneficial in patients who have received 5-FU-based CRT. The expression levels of four genes, HIF1A, MTHFD1, GGH and TYMS, in tumor tissues can predict the response to preoperative CRT including either S-1 or UFT/LV. In particular, the gene expression level of GGH in tumor tissues may be a useful biomarker for the appropriate use of S-1 and UFT/LV in CRT.

Topics: Adenocarcinoma; Adult; Aged; Antidotes; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Chemoradiotherapy; Combined Modality Therapy; Drug Combinations; Female; Fluorouracil; gamma-Glutamyl Hydrolase; Gene Expression Regulation, Neoplastic; Humans; Leucovorin; Male; Middle Aged; Oxonic Acid; Rectal Neoplasms; Reproducibility of Results; Tegafur; Treatment Outcome

The patient was a 66-year-old woman with a history of right breast cancer 20 years prior. Her chief complaint was hematochezia, and she was diagnosed as having rectal cancer. She underwent laparoscopic high anterior resection. We made a diagnosis of moderately differentiated adenocarcinoma, type 2, 25×20 mm, pMP, pN0, Stage I, KRAS being wild-type. Multiple liver metastases were detected 6 months after the surgery. Tumor contacted with grison. The tumor was not completely resected as evidenced by the small liver remnant volume. Conversion therapy was administered, and the patient received 6 courses of FOLFIRI plus cetuximab therapy. Alopecia and grade 1 eruption were observed as adverse effects of the chemotherapy. The tumor size was reduced, and we resected the tumor by performing right lobectomy and partial hepatectomy. At 1 year 3 months after surgery, no recurrence was observed.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cetuximab; Colectomy; Combined Modality Therapy; Female; Fluorouracil; Hepatectomy; Humans; Leucovorin; Liver Neoplasms; Rectal Neoplasms; Treatment Outcome

We report a case of locally advanced rectal cancer, treated effectively with chemotherapy consisting of mFOLFOX6 combined with radiotherapy. A 63-year-old man was admitted to our hospital in March 2012 for diarrhea and anal and perineal pain. Advanced rectal cancer with invasion ofthe right perineum was diagnosed based on computer tomography(CT) findings. Surgery was performed; however, the rectal cancer was unresectable. A sigmoid colostomy was performed, and a central venous port was implanted. In April 2012, the patient was treated with chemotherapy using 3 courses ofmFOLFOX6 and concurrent radiotherapy. Radiotherapy at 2 Gy/day was administered 25 times(total dose, 50 Gy). After chemoradiotherapy, the patient underwent 3 courses ofmFOLFOX6 as an additional therapy. By June 2012, CT showed resolution ofthe tumor in the right perineum and a marked decrease in the size ofthe primary rectal cancer. Because the patient refused surgery, we started treatment with combination chemotherapy using oral S-1 and intravenous CPT-11 in August 2012. After 18 courses, the treatment was changed to oral administration ofS -1 alone, which was continued for 1 year. The patient remained well without recurrence for 54 months since the original diagnosis. Therefore, chemoradiotherapy with mFOLFOX6 is a possible option for the management of advanced rectal cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemoradiotherapy; Drug Combinations; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxonic Acid; Rectal Neoplasms; Tegafur; Treatment Outcome

Platinum resistance enhances DNA damage repair through nucleotide excision repair mechanisms involving the excision repair cross-complementing group 1 (ERCC1), X-ray cross-complementing group 1 (XRCC1), and excision repair cross-complementing group 2 (ERCC2). We evaluated the correlation between the expression of these three DNA repair genes and clinical outcomes in patients with rectal cancer receiving FOLFOX-based preoperative chemoradiotherapy (CRT).. Using immunohistochemistry, we examined the expression of ERCC1, ERCC2, and XRCC1 in pre-CRT cancer tissues from 86 patients with rectal cancer who had undergone curative resection and preoperative CRT with FOLFOX-4 to identify potential predictors of clinical outcomes.. Following CRT, 57 and 29 patients were classified as responders (pathological tumor regression grade TRG 0 and TRG 1) and poor responders (TRG 2 and TRG 3), respectively. The multivariate analysis revealed that ERCC1 overexpression was correlated with a poor CRT response [p < 0.0001; odds ratio (OR), 9.397; 95% confidence interval (CI) 2.721-32.457]. Furthermore, a poor response to CRT (pathological TRG of 2-3) (p = 0.18; OR 5.685; 95% CI 1.349-23.954) and abnormal pre-CRT serum carcinoembryonic antigen levels (>5 ng/mL) (p = 0.03; OR 6.288; 95% CI 1.198-33.006) were independent predictors of postoperative relapse. By contrast, ERCC2 and XRCC1 expression did not play predictive roles in the analyzed patients.. ERCC1 overexpression is associated with a poor preoperative CRT response in patients with rectal cancer receiving FOLFOX-based preoperative CRT. ERCC1 is a potential biomarker for identifying patients who can benefit from customized treatment programs.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; DNA-Binding Proteins; Endonucleases; Female; Fluorouracil; Humans; Immunohistochemistry; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Rectal Neoplasms; Treatment Outcome; X-ray Repair Cross Complementing Protein 1; Xeroderma Pigmentosum Group D Protein

We present a case of bilateral lymph node metastases of rectal cancer treated with chemotherapy and surgery. The patient was a 65-year-old man with upper rectal cancer. Laparoscopic low anterior resection(LAR)was performed. Pathological findings were tub2>por>muc, pT3, ly2, v3, pN2, pM0. Six months after surgery, the CEA level was elevated. CT and PET-CT confirmed bilateral metastasis to the lymph nodes. Five courses of FOLFOX4 plus bevacizumab were administered, and then, we performed laparoscopic bilateral lymph node dissection. Pathological assessments confirmed scarring and fibrosis, that is, a pathological complete response(pCR)was achieved. Two years and 6 months after surgery, no recurrence was detected. After chemotherapy or chemoradiotherapy, we should perform surgery to prevent local recurrence, especially to the lateral lymph nodes.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Combined Modality Therapy; Fluorouracil; Humans; Laparoscopy; Leucovorin; Lymphatic Metastasis; Male; Organoplatinum Compounds; Rectal Neoplasms; Recurrence

A 74-year-old male had undergone laparoscopic abdominoperineal resection for lower rectal cancer in July 2009. The pathological diagnosis was T2, N0, M0, pStage I (TNM 7th). Because of pathological venous invasion, adjuvant chemotherapy with Tegafur-uracil(UFT)plus Leucovorin for a year was performed. A CT examination revealed slowly growing peripheral right internal iliaclymph node. PET-CT demonstrated a 20mm right lateral lymph node(LLN)metastasis without other distant metastases. On diagnosis of solitary LLN metastasis of rectal cancer, the patient underwent surgical lymph node resection in September 2014. The pathological diagnosis was lymph node metastasis from rectal cancer. Subsequently, the patient received mFOLFOX6 adjuvant chemotherapy for 6 months. The patient remains alive without any recurrence 31 months after the second surgical treatment. lt is important to consider that LLN metastasis of Stage I rectal cancer might still occur a long time after the curative operation.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Humans; Leucovorin; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Rectal Neoplasms; Tegafur

A-58-year-old man was admitted to other hospital with complaints of anal pain and bloody stools, diagnosed as rectal cancer with invasion to prostate, and performed sigmoid colostomy. After taking 6 courses of mFOLFOX6 as preoperative chemotherapy, he introduced our hospital for the purpose of operation. Preoperative evaluation of chemotherapy was PR, but infiltration of the prostate remained. Therefore, laparoscopic abdomino-perineal resection of rectum, prostatectomy and urethral reconstruction by urethral-bladder anastomosis were performed. Postoperative course was good and he was discharged on 10 days after surgery. Currently 2 years after surgery, he has no dysurea and relapse free survival. This procedure was considered to be a very useful technique in that a good operative field and reliable resection can be obtained.

Topics: Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Laparoscopy; Leucovorin; Male; Middle Aged; Neoplasm Invasiveness; Organoplatinum Compounds; Prognosis; Prostate; Prostatectomy; Rectal Neoplasms

We experienced 2 cases in which ramucirumab plus FOLFIRI as second-line treatment was beneficial. Case 1 was a 67-yearold man, underwent panitumumab plus mFOLFOX6 as first-line treatment for unresectable rectal cancer with ureteral invasion and multiple liver metastases, but the disease became worse at 9.3 months. We changed to ramucirumab plus FOLFIRI as second-line treatment. After 2 courses, a grade 3 febrile neutropenia was observed, but treatment was beneficial and continued administration for 9 months or more. Case 2 was a 73-year-old man who underwent panitumumab plus mFOLFOX6 as first-line treatment after cytoreductive surgery of the primary lesion for sigmoid colon cancer with intestinal obstruction and liver metastasis, but the disease became worse at 4.7 months. Upon entering ramucirumab plus FOLFIRI therapy, the metastatic lesions shrinked remarkably. Adverse events of grade 3 or higher were not observed and finally continued administration for 7.9 months. It was suggested that ramucirumab plus FOLFIRI combination therapy for metastatic colorectal cancer could be an effective as second-line treatment.

Topics: Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Disease Progression; Drug Resistance, Neoplasm; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Ramucirumab; Rectal Neoplasms; Sigmoid Neoplasms

Following preoperative chemoradiation and surgery, many patients with stage II to III rectal cancer are unable to tolerate full-dose adjuvant chemotherapy. BrUOG R-224 was designed to assess the impact of COmplete Neoadjuvant Treatment for REctal cancer (CONTRE), primary chemotherapy followed by chemoradiation and surgery, on treatment delivery, toxicities, and pathologic response at surgery.. Patients with clinical stage II to III (T3 to T4 and/or N1 to N2) rectal cancer received 8 cycles of modified FOLFOX6 followed by capecitabine 825 mg/m bid concurrent with 50.4 Gy intensity-modulated radiation therapy. Surgery was performed 6 to 10 weeks after chemoradiation.. Thirty-nine patients were enrolled between August 2010 and June 2013. Median age was 61 years (30 to 79 y); 7 patients (18%) were clinical stage II and 32 (82%) stage III. Thirty-six patients (92%) received all 8 cycles of mFOLFOX6, of whom 35 completed subsequent chemoradiation; thus 89% of patients received CONTRE as planned. No unexpected toxicities were reported. All patients had resolution of bleeding and improvement of obstructive symptoms, with no complications requiring surgical intervention. Pathologic complete response (ypT0N0) was demonstrated in 13 patients (33%; 95% CI, 18.24%-47.76%).. CONTRE seems to be a well-tolerated alternative to the current standard treatment sequence. Evaluating its impact on long-term outcomes would require a large randomized trial, but using pathologic response as an endpoint, it could serve as a platform for assessing the addition of novel agents to preoperative treatment in stage II to III rectal cancer.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemoradiotherapy; Chemotherapy, Adjuvant; Digestive System Surgical Procedures; Drug Administration Schedule; Female; Fluorouracil; Humans; Induction Chemotherapy; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Radiotherapy, Intensity-Modulated; Rectal Neoplasms; Treatment Outcome

Patients with locally advanced rectal cancer (LARC) receiving neoadjuvant chemoradiation (nCRT) can have a complete pathologic response (pCR), and are given postoperative adjuvant chemotherapy (ACT).. A prospectively maintained outcomes database was queried for patients who had pCR to nCRT for LARC from 2000 to 2012. Local recurrence and survival were analyzed according to whether patients received ACT.. We identified 139 patients and excluded 9 due to lack of follow-up. Mean age was 58.9 ± 11.8 years. 83 patients (63.8%) did not receive ACT (Group A) and 47 (36.2%) did (Group B). Mean follow-up was 5.7 ± 3 and 5.6 ± 3.5 years for Groups A and B respectively (p = 0.51). Groups were comparable in age, gender, tumor differentiation, and clinical staging. There were no differences in oncological outcomes.. Avoiding routine use of ACT in patients with a pCR may be considered. Further justification of this approach warrants prospective randomized studies.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Chemotherapy, Adjuvant; Disease-Free Survival; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Metastasis; Neoplasm Recurrence, Local; Prospective Studies; Rectal Neoplasms

Topics: Fluorouracil; Humans; Leucovorin; Neoadjuvant Therapy; Prostatic Neoplasms; Rectal Neoplasms

Topics: Fluorouracil; Humans; Leucovorin; Neoadjuvant Therapy; Rectal Neoplasms; Research Design

Topics: Fluorouracil; Humans; Leucovorin; Neoadjuvant Therapy; Rectal Neoplasms; Rectum

Nonoperative management for patients with rectal cancer who have achieved a clinical complete response after chemoradiotherapy is becoming increasingly important in recent years. However, the definition of and modality used for patients with clinical complete response differ greatly between institutions, and the role of endoscopic assessment as a nonoperative approach has not been fully investigated.. This study aimed to investigate the ability of endoscopic assessments to predict pathological regression of rectal cancer after chemoradiotherapy and the applicability of these assessments for the watchful waiting approach.. This was a retrospective comparative study.. This study was conducted at a single referral hospital.. A total of 198 patients with rectal cancer underwent preoperative endoscopic assessments after chemoradiotherapy. Of them, 186 patients underwent radical surgery with lymph node dissection.. The histopathological findings of resected tissues were compared with the preoperative endoscopic findings. Twelve patients refused radical surgery and chose watchful waiting; their outcomes were compared with the outcomes of patients who underwent radical surgery.. The endoscopic criteria correlated well with tumor regression grading. The sensitivity and specificity for a pathological complete response were 65.0% to 87.1% and 39.1% to 78.3%. However, endoscopic assessment could not fully discriminate pathological complete responses, and the outcomes of patients who underwent watchful waiting were considerably poorer than the patients who underwent radical surgery. Eventually, 41.7% of the patients who underwent watchful waiting experienced uncontrollable local failure, and many of these occurrences were observed more than 3 years after chemoradiotherapy.. The number of the patients treated with the watchful waiting strategy was limited, and the selection was not randomized.. Although endoscopic assessment after chemoradiotherapy correlated with pathological response, it is unsuitable for surveillance of patients treated via a nonoperative approach. Incorporation of a "watchful waiting" strategy without establishing proper surveillance protocols and salvage strategies might result in poor local control.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoembryonic Antigen; Chemoradiotherapy; Colonoscopy; Digestive System Surgical Procedures; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Logistic Models; Lymph Node Excision; Male; Middle Aged; Multivariate Analysis; Neoadjuvant Therapy; Neoplasm Staging; Odds Ratio; Pyridines; Rectal Neoplasms; Rectum; Remission Induction; Retrospective Studies; Tegafur; Treatment Outcome; Watchful Waiting

In this era of oxaliplatin-based adjuvant therapy, the optimal sequence in which chemoradiotherapy should be administered for pathological stage N2 rectal cancer is unknown. The aim of this study was to investigate this sequence.. In the primary adjuvant concurrent chemoradiotherapy (A-CRT) group (n = 71), postoperative concurrent chemoradiotherapy was administered before adjuvant chemotherapy. In the primary adjuvant chemotherapy (A-CT) group (n = 43), postoperative concurrent chemoradiotherapy was administered during or after adjuvant chemotherapy. Postoperative radiotherapy comprised 45-50.4 Gy in 25-28 fractions. Concurrent chemotherapy comprised two cycles of oral capecitabine (1,600 mg/m. Between June 2005 and December 2013, data for 114 qualified rectal cancer patients were analyzed. The percentages of patients in whom treatment failed in the A-CRT and A-CT groups were 33.8% and 16.3%, respectively (p = 0.042). More patients had distant metastases in the A-CRT group than in the A-CT group (32.4% vs. 14.3%, p = 0.028). Multivariate analysis indicated that the sequence in which chemoradiotherapy was administered (A-CT vs. A-CRT) was an independent prognostic factor for both estimated disease-free survival [hazard ratio (HR) 0.345, 95% confidence interval (CI) 0.137-0.868, p = 0.024] and estimated distant metastasis-free survival (HR 0.366, 95% CI 0.143-0.938, p = 0.036).. In pathological stage N2 rectal cancer patients, administering adjuvant chemotherapy before chemoradiotherapy led to a lower rate of treatment failure, especially with respect to distant metastasis. Adjuvant chemotherapy prescribed as early as possible might benefit this cohort of patients in this era of oxaliplatin-based adjuvant therapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemoradiotherapy, Adjuvant; Chemotherapy, Adjuvant; Disease-Free Survival; Dose Fractionation, Radiation; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms; Treatment Outcome; Young Adult

Optimal initial management of rectal carcinoma with synchronous metastases (RCSM) is controversial - both for patients being treated with curative and palliative intent. This study aims to evaluate the use of an upfront treatment strategy combining FOLFOX chemotherapy with split-course pelvic chemoradiation (FOLFOX + CRT) for patients with RCSM.. An analysis of all patients who commenced treatment with FOLFOX + CRT at our institutions between January 2009 and June 2014 was performed. The regimen consisted of a total of 12 weeks of treatment with split-course pelvic chemoradiation (50.4Gy with concurrent oxaliplatin and 5-FU) alternating with FOLFOX chemotherapy. Restaging imaging was performed following treatment, with subsequent management as per local standard of care.. 78 patients (15 with resectable liver-only metastases) were identified. 77 (99%) completed at least 45Gy of radiation and 87% completed ≥75% of planned dose intensity of both oxaliplatin and 5FU. Two (2.6%) patients died within 30 days of treatment. Rates of radiological complete or partial response for local and metastatic disease were 90% and 66%, respectively. 24% patients had radiological disease progression of metastatic disease. Median overall survival for patients with unresectable metastatic disease at baseline was 23 months (95%CI: 19-28). 12 patients underwent radical surgery to both the rectum and liver and had an estimated 3-year overall survival rate of 62% (95%CI: 37-100). For those patients who did not proceed to rectal surgery, only 7% required palliative re-irradiation or surgery at a later date and all >20months from initial treatment.. In patients with unresectable metastatic disease, FOLFOX + CRT provides durable pelvic control for the majority without the need for additional local treatment. For patients with an advanced primary tumor and synchronous resectable liver-only metastases, FOLFOX + CRT can be considered a feasible and tolerable upfront treatment option.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoplasms, Multiple Primary; Organoplatinum Compounds; Oxaliplatin; Prognosis; Rectal Neoplasms; Retrospective Studies; Survival Rate

The aim of this study was to investigate metabolic and textural parameters from pretreatment [(18)F]FDG PET/CT scans for the prediction of neoadjuvant radiation chemotherapy response and 3-year disease-free survival (DFS) in patients with locally advanced rectal cancer (LARC).. We performed a retrospective review of 74 patients diagnosed with LARC who were initially examined with [(18)F]FDG PET/CT, and who underwent neoadjuvant radiation chemotherapy followed by complete resection. The standardized uptake value (mean, peak, and maximum), metabolic volume (MV), and total lesion glycolysis of rectal cancer lesions were calculated using the isocontour method with various thresholds. Using three-dimensional textural analysis, about 50 textural features were calculated for PET images. Response to neoadjuvant radiation chemotherapy, as assessed by histological tumour regression grading (TRG) after surgery and 3-year DFS, was evaluated using univariate/multivariate binary logistic regression and univariate/multivariate Cox regression analyses.. MVs calculated using the thresholds mean standardized uptake value of the liver + two standard deviations (SDs), and mean standard uptake of the liver + three SDs were significantly associated with TRG. Textural parameters from histogram-based and co-occurrence analysis were significantly associated with TRG. However, multivariate analysis revealed that none of these parameters had any significance. On the other hand, MV calculated using various thresholds was significantly associated with 3-year DFS, and MV calculated using a higher threshold tended to be more strongly associated with 3-year DFS. In addition, textural parameters including kurtosis of the absolute gradient (GrKurtosis) were significantly associated with 3-year DFS. Multivariate analysis revealed that GrKurtosis could be a prognostic factor for 3-year DFS.. Metabolic and textural parameters from initial [(18)F]FDG PET/CT scans could be indexes to assess tumour heterogeneity for the prediction of neoadjuvant radiation chemotherapy response and recurrence in LARC.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Capecitabine; Chemoradiotherapy; Disease-Free Survival; Female; Fluorodeoxyglucose F18; Fluorouracil; Humans; Imaging, Three-Dimensional; Leucovorin; Male; Middle Aged; Multimodal Imaging; Neoadjuvant Therapy; Positron-Emission Tomography; Prognosis; Proportional Hazards Models; Radiopharmaceuticals; Rectal Neoplasms; Retrospective Studies; Tomography, X-Ray Computed; Treatment Outcome

Preoperative chemoradiotherapy (CRT) is widely used in the treatment of locally advanced rectal cancer (LARC). Pathological response to CRT has been shown to be a potential prognostic predictor in rectal cancer patients. The aim of this study was to determine the prognostic significance of pathological response to preoperative CRT in LARC patients.. Thirty-two patients with LARC were retrospectively analyzed to determine the relationships of pathological response and clinicopathological characteristics to survival outcomes. Patients received CRT with tegafur/uracil and leucovorin. Radiotherapy was administered in fractions of 1.8 Gy/day and 5 days per week. The total dose of radiation delivered was 45 Gy.. All patients underwent total mesorectal excision with lymph node dissections after CRT, and resected specimens were examined pathologically. Four patients showed pathological complete response, 14 showed good response, and 14 showed poor response. Pathological complete or good response was associated with longer survival (P = 0.041). Clinicopathological factors excluding gender were not correlated with outcome. No factor was associated with recurrence.. Pathological response to preoperative CRT may be a useful prognostic predictor in patients with LARC.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Dose Fractionation, Radiation; Female; Humans; Leucovorin; Lymph Node Excision; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Predictive Value of Tests; Preoperative Care; Prognosis; Rectal Neoplasms; Remission Induction; Retrospective Studies; Survival Rate; Tegafur

Neoadjuvant concurrent chemoradiotherapy combined with total mesorectal excision is the main treatment for patients with locally advanced rectal cancer (LARC). However, because distant metastasis remains the major challenge in the management of LARC, we proposed an additional one cycle of chemotherapy before surgery to improve systemic control.. One hundred sixty-eight patients with clinical stage II and III rectal cancer were enrolled at Kyungpook National University Medical Center (Daegu, Korea) between January 2011 and December 2013 and were considered the study group. In addition, 160 patients were retrospectively reviewed as the historical control group. All the patients underwent total mesorectal excision at 8 weeks after completing the radiotherapy and receiving a total of six cycles of 5-fluorouracil plus leucovorin.. Overall, 155 (96.9%) of the 168 patients completed their planned six cycles of study treatment. Dose modification at any cycle was observed in 18 patients (10.7%). The grade 3 to 4 treatment-related toxicity rate was 27.3%, and the most common grade 3 to 4 hematologic adverse event was neutropenia. With a median follow-up duration of 38 months, the estimated 3-year disease-free survival and OS rates were 79.5 and 86.9%, respectively.. Adding one cycle of chemotherapy during the resting period between chemoradiotherapy and surgery was found to be feasible in patients with LARC in terms of the chemotherapy-related adverse events and postoperative complications. These results warrant further investigation in future prospective randomized trials.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Case-Control Studies; Chemoradiotherapy, Adjuvant; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Pilot Projects; Prognosis; Rectal Neoplasms; Retrospective Studies; Survival Rate

A 71-year-old male patient began FOLFOX6 plus panitumumab treatment for unresectable recurrent rectal cancer. He developed thrombocytopenia after 2 courses of treatment and therefore a platelet transfusion was performed. The day after transfusion, the patient developed jaundice and hematuria. His lactate dehydrogenase levels had increased and a peripheral blood smear review revealed the presence of schistocytes. Anti-ADAMTS13 antibodies were present, and there was a reduction in ADAMTS13 activity. The patient was diagnosed with thrombotic thrombocytopenic purpura and treated with a plasma exchange. The day after the plasma exchange, his clinical condition rapidly worsened and he died. Thrombocytopenia due to chemotherapy often appears as myelosuppression. If conditions such as jaundice, indirect bilirubinemia, or hematuria appear during the course of chemotherapy, this condition must be considered as a differential diagnosis.

Topics: ADAM Proteins; ADAMTS13 Protein; Aged; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Fatal Outcome; Fluorouracil; Humans; Leucovorin; Male; Organoplatinum Compounds; Panitumumab; Plasma Exchange; Purpura, Thrombotic Thrombocytopenic; Rectal Neoplasms; Recurrence

To quantify ensuing bone marrow (BM) suppression during postoperative chemotherapy resulting from preoperative chemoradiation (CRT) therapy for rectal cancer.. We retrospectively evaluated 35 patients treated with preoperative CRT followed by postoperative 5-Fluorouracil and oxaliplatin (OxF) chemotherapy for locally advanced rectal cancer. The pelvic bone marrow (PBM) was divided into ilium (IBM), lower pelvis (LPBM), and lumbosacrum (LSBM). Dose volume histograms (DVH) measured the mean doses and percentage of BM volume receiving between 5-40 Gy (i.e.: PBM-V5, LPBM-V5). The Wilcoxon signed rank tests evaluated the differences in absolute hematologic nadirs during neoadjuvant vs. adjuvant treatment. Logistic regressions evaluated the association between dosimetric parameters and ≥ grade 3 hematologic toxicity (HT3) and hematologic event (HE) defined as ≥ grade 2 HT and a dose reduction in OxF. Receiver Operator Characteristic (ROC) curves were constructed to determine optimal threshold values leading to HT3.. During OxF chemotherapy, 40.0% (n=14) and 48% (n=17) of rectal cancer patients experienced HT3 and HE, respectively. On multivariable logistic regression, increasing pelvic mean dose (PMD) and lower pelvis mean dose (LPMD) along with increasing PBM-V (25-40), LPBM-V25, and LPBM-V40 were significantly associated with HT3 and/or HE during postoperative chemotherapy. Exceeding ≥36.6 Gy to the PMD and ≥32.6 Gy to the LPMD strongly correlated with causing HT3 during postoperative chemotherapy.. Neoadjuvant RT for rectal cancer has lasting effects on the pelvic BM, which are demonstrable during adjuvant OxF. Sparing of the BM during preoperative CRT can aid in reducing significant hematologic adverse events and aid in tolerance of postoperative chemotherapy.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Bone Marrow Diseases; Capecitabine; Chemoradiotherapy; Female; Fluorouracil; Humans; Ilium; Leucovorin; Leukopenia; Logistic Models; Lumbar Vertebrae; Male; Middle Aged; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Pelvic Bones; Preoperative Care; Rectal Neoplasms; Retrospective Studies; ROC Curve; Sacrum; Statistics, Nonparametric; Thrombocytopenia

The effect of individual dose adjustment of 5-fluorouracil (5-FU) based on pharmacokinetic monitoring on the outcome of FOLFOX for metastatic colorectal cancer was analyzed retrospectively.. Twenty patients with metastatic colorectal cancer underwent FOLFOX chemotherapy from January 2005 to December 2013 at the Niitsu Medical Center Hospital. The sample group included 11 patients in whom 5-FU doses were adjusted individually based on pharmacokinetic monitoring according to an algorithm to maintain the area under the curve (AUC) in the range of 20-25 mg·h/L (Group A) and 9 patients in whom 5-FU doses were adjusted conventionally based on body surface area (Group B).. The objective response rate was 63% and 33% in Group A and Group B, respectively (p=0.174). The median overall survival was 34 months and 14 months in Group A and Group B, respectively (p=0.036). There were 4 cases of Grade 3 toxicity (2 in Group A, 2 in Group B; p=0.636) and no cases of Grade 4 toxicity or treatment-related death.. Pharmacokinetically guided dose adjustment of 5-FU may improve the outcome of FOLFOX for metastatic colorectal cancer.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Rectal Neoplasms; Recurrence; Retrospective Studies

This study was aimed to assess the feasibility and short-term outcomes of adjuvant systemic chemotherapy with either S-1/oxaliplatin (SOX) or mFOLFOX6 (FOLFOX)after curative resection of distant metastases from colorectal cancer. We retrospectively examined 16 patients who underwent R0 resection of colorectal metastases, including the liver (n=6), lung (n=5), lymph node (n=3), and peritoneum (n=2), followed by chemotherapy with SOX (n=7) or FOLFOX (n=9) until disease progression. The mean recurrence-free survival was 13.2 months in the SOX group and 16.9 months in the FOLFOX group. The mean overall survival was 17.9 and 22.9 months, respectively. The number of given courses were 6.5 and 11.0, respectively. Although sensory neuropathy was observed in 38% of the patients, relative dose intensity was higher than 80%. Adjuvant chemotherapy with SOX or FOLFOX was feasible and effective. Further randomized prospective trials are warranted to confirm these results.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colonic Neoplasms; Drug Combinations; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Rectal Neoplasms; Recurrence; Retrospective Studies; Tegafur

A 63-year-old man visited our hospital with pain on micturition and was found to have a large rectal tumor with urinary bladder invasion on enhanced abdominal computed tomography (CT). The tumor appeared to be unresectable at presentation; thus, sigmoid colostomy was performed and chemotherapy was initiated. The tumor was found to be EGFR-positive and contained a wild-type KRAS. The mFOLFOX6 plus cetuximab (c-mab) regimen was initiated. The follow-up CT scan showed good tumor shrinkage after 4 courses of chemotherapy; 4 additional courses were administered. The tumor eventually regressed by more than 60% and was judged to be resectable. High anterior resection of the rectum with partial resection of the bladder was performed. Abdominal wall metastasis was detected 8 months after surgery, and additional resection was performed. The patient remained well with no other recurrence 8 months after the high anterior resection. Although chemoradiotherapy is the standard preoperative treatment of locally advanced rectal cancer, systemic therapy is effective in certain cases such as substantial tumor invasion of adjacent organs or metastasis. Here, we present a case of rectal cancer that became curatively resectable after preoperative chemotherapy with mFOLFOX6 plus c-mab.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cetuximab; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Invasiveness; Organoplatinum Compounds; Rectal Neoplasms; Treatment Outcome

Good oncologic outcomes, demonstrated by a complete pathologic response after preoperative chemoradiotherapy (PCRT), have led to local excision (LE) in selected patients with rectal cancer. We evaluated the oncologic safety of LE compared with total mesorectal excision (TME) in patients with ypT0-T1 rectal cancer.A retrospective review of 304 patients who underwent PCRT, followed by LE or TME, for ypT0-T1 rectal cancer was performed. Propensity scores were computed and used to match groups (LE:TME = 1:1), and analysis of disease-free survival (DFS) and overall survival (OS) was made by comparing patients who underwent LE or TME. Prognostic factors of relapse were analyzed for all patients.Tumor categories were ypT0 in 25 (61.9%) cases, ypTis in 6 (14.3%) cases, and ypT1 in 11 (26.2%) cases for the LE group, and ypT0 in 28 (66.7%) cases, ypTis in 4 (9.5%) cases, and ypT1 in 10 (23.8%) cases for the matched TME patients. There was no significant difference between the matched LE and TME groups in relapse (4.8% and 7.14%, respectively; P = 0.646), 5-year DFS (95.2% vs 91.6%; P = 0.33) and 5-year OS (96.6% vs 88.0%; P = 0.238). In the multivariate Cox regression analysis, tumor distance from the anal verge (hazard ratio [HR] = 0.78; 95% confidence interval (CI) = 0.616-0.992) and the tumor grade (HR = 4.29; 95% CI = 1.430-12.886) were significantly associated with the recurrence risk.LE results in oncologic outcomes that are comparable to those achieved by TME in selected patients with ypT0-T1 rectal cancer after PCRT.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemoradiotherapy, Adjuvant; Digestive System Surgical Procedures; Disease-Free Survival; Dose Fractionation, Radiation; Female; Fluorouracil; Humans; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Grading; Neoplasm Recurrence, Local; Neoplasm Staging; Propensity Score; Rectal Neoplasms; Retrospective Studies; Survival Rate

We report a case of advanced colon cancer that was effectively treated with mFOLFOX6 plus panitumumab combination chemotherapy. The patient was a 54-year-old man who had type 2 colon cancer of the rectum. An abdominal CT scan demonstrated rectal cancer with bulky lymph node metastasis and 1 hepatic node (rectal cancer SI [bladder retroperitoneum], N2M0H1P0, cStage IV). He was treated with mFOLFOX6 plus panitumumab as neoadjuvant chemotherapy. After 4 courses of chemotherapy, CT revealed that the primary lesion and regional metastatic lymph nodes had reduced in size (rectal cancer A, N1H1P0M0, cStage IV). Anterior rectal resection with D3 nodal dissection and left lateral segmentectomy of the liver was performed. The histological diagnosis was tubular adenocarcinoma (tub2-1), int, INF a, pMP, ly0, v0, pDM0, pPM0, R0. He was treated with 4 courses of mFOLFOX6 after surgery. The patient has been in good health without a recurrence for 2 years and 5 months after surgery. This case suggests that induction chemotherapy with mFOLFOX6 plus panitumumab is a potentially effective regimen for advanced colon cancer.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Induction Chemotherapy; Leucovorin; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Panitumumab; Rectal Neoplasms

To investigate the association of CD133 expression in rectal cancer tissues with neoadjuvant chemoradiotherapy (nCRT) and tumor regression grading (TRG) after nCRT.. Radical resected rectal cancer specimens and clinicopathological data of 105 patients, including 60 men and 45 women with median age of 59 years, diagnosed as locally advanced rectal cancer in Peking Union Medical College Hospital from January 2008 to December 2014 were collected retrospectively. Thirty-nine and 66 cases were histologically classified as good-moderate and poor differentiation respectively. Sixty-eight and 37 cases were clinically graded as stage I(-II( and III(-IIII( in preoperative assessment respectively. NCRT was administered in 61 cases before surgery (nCRT group). The nCRT consisted of preoperative pelvic radiotherapy using 50 Gy (2 Gy once, for 25 sessions) with FOLFOX regimen (5-fluorouracil plus oxaliplatin) for 2-3 cycles or XELOX regimen (capecitabine plus oxaliplatin) for 2 cycles. Patients underwent surgery after 6 courses of nCRT, and then received the same previous chemotherapy regimen. In nCRT group, biopsy specimens before nCRT were obtained in 45 cases. Forty-four cases received surgery alone without nCRT (surgery alone group). CD133 expression was tested by immunohistochemical Envision two-step methods. The histological TRG evaluation was performed in the nCRT group. TRG score 0-2 was defined as insensitivity to nCRT, whereas TRG score 3-4 was defined as sensitivity. CD133 expression in rectal cancer samples before and after nCRT was compared. Association of CD133 expression with TRG after nCRT was examined.. No significant differences of baseline parameters were found between nCRT group and surgery alone group (all P>0.05). The positive rate of CD133 in nCRT group was 70.4%(43/61,) which was significantly higher than that in surgery alone group (47.7%, 21/44)(χ(2)=5.566, P=0.018) and that in biopsy samples before nCRT group (44.4%, 20/45)(χ(2)=7.287, P=0.007). Twenty-two cases (36.1%, 22/61) in nCRT group had TRG score of 3-4 . Among these 22 cases, 11 cases were negative CD133, and constituted 61.1% (11/18) of all CD133-low expression cases in nCRT group, whereas the other 11 cases were positive CD133, and constituted 25.6%(11/43) of all CD133-high expression cases in nCRT group (χ(2)=6.974, P=0.008).. The CD133 expression up-regulates markedly in rectal cancer after nCRT and nCRT may have potential positive modulation on CD133 expression. CD133-positive cancer reveals lower response to nCRT, suggesting CD133 may be a potential target for improving efficacy of nCRT in rectal cancer.

Topics: AC133 Antigen; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemoradiotherapy; Deoxycytidine; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Oxaloacetates; Rectal Neoplasms

A 51-year-old man underwent abdominoperineal resection for advanced rectal cancer at a hospital. He attended our outpatient clinic 58 months later with pain in the external genitalia, and was diagnosed with local pelvic recurrence and metastasis to the para-aortic lymph node and both adrenal glands. He received a total of 30 Gy of radiation for analgesia; subsequently, chemotherapy(mFOLFOX6 plus bevacizumab)was initiated. However, extreme left buttock and left femoral pain developed after the 6 courses of chemotherapy. Abdominal CT revealed Fournier's gangrene caused by small intestinal perforation. Emergency drainage under spinal anesthesia was immediately performed. Two additional drainage procedures were required thereafter and an ileostomy was constructed. The patient was discharged 100 days after the initial drainage. This is an extremely rare example of a bevacizumab-related small intestinal perforation that developed into Fournier's gan- grene.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Chemoradiotherapy; Drainage; Fatal Outcome; Fluorouracil; Fournier Gangrene; Humans; Intestinal Perforation; Intestine, Small; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Rectal Neoplasms

To evaluate the treatment outcomes of patients with locally advanced rectal cancer treated with preoperative concurrent chemoradiotherapy (CCRT) or combined chemotherapy together with radiotherapy (CMTRT) without surgery.. A total of 84 patients with locally advanced rectal adenocarcinoma (stage II or III) between January 1st, 2003 and December 31st, 2013 were enrolled, 48 treated with preoperative CCRT (Gr.I) and 36 with combined chemotherapy and radiotherapy (CMTRT) without surgery (Gr.II). The chemotherapeutic agents used concurrent with radiotherapy were either 5fluorouracil short infusion plus leucovorin and/or capecitabine or 5fluorouracil infusion alone. All patients received pelvic irradiation.. There were 5 patients (10.4%) with a complete pathological response. The 3 yearoverall survival rates were 83.2% in Gr.I and 24.8 % in Gr.II (p<0.01). The respective 5 yearoverall survival rates were 70.3% and 0% (p<0.01). The 5 yearoverall survival rates in Gr.I for patients who received surgery within 56 days after complete CCRT as compared to more than 56 days were 69.5% and 65.1% (p=0.91). Preoperative CCRT used for 12 of 30 patients in Gr.I (40%) with lower rectal cancer demonstrated that in preoperative CCRT a sphincter sparing procedure can be performed.. The results of treatment with preoperative CCRT for locally advanced rectal cancer showed comparable rates of overall survival and sphincter sparing procedures as compared to previous studies.

Topics: Adenocarcinoma; Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemoradiotherapy; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Preoperative Period; Radiotherapy Dosage; Rectal Neoplasms; Survival Rate; Treatment Outcome; Young Adult

A 68-year-old man was diagnosed with rectal cancer on colonoscopy and liver metastasis of rectal cancer on abdominal computed tomography(CT). He underwent resection of the primary lesion, and the final diagnosis was A, N1, H1, P0, M0, fStage IV. After resection of the primary lesion, he received chemotherapy with mFOLFOX6 plus cetuximab. After 6 courses of the treatment, CT revealed partial response of the liver metastasis. Then, he underwent resection of the liver metastasis. The pathological finding revealed that the resected specimen had no cancer cells. After resection of the liver metastasis, he received 6 courses of chemotherapy with the same regimen, and relapse-free survival continues until the time of this writing.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cetuximab; Combined Modality Therapy; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Organoplatinum Compounds; Rectal Neoplasms

After local excision of early rectal cancer, revision radical resection is recommended for patients with high-risk pathologic stage T1 (pT1) or pT2 cancer, but the revision procedure has high morbidity rates. We evaluated the efficacy of adjuvant concurrent chemoradiotherapy (CCRT) for reducing recurrence after local excision in these patients.. Eighty-three patients with high-risk pT1 or pT2 rectal cancer underwent postoperative adjuvant CCRT after local excision. We defined high-risk features as pT1 having tumor size ≤3 cm, and/or resection margin (RM) ≤3 mm, and/or lymphovascular invasion (LVI), and/or non-full thickness excision such as endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD), or unknown records regarding those features, or pT2 cancer. Radiotherapy was administered with a median dose of 50.4 Gy in 1.8 Gy fraction size over 5-7 weeks. Concurrent 5-fluorouracil and leucovorin were administered for 4 days in the first and fifth weeks of radiotherapy.. The median interval between local excision and radiotherapy was 34 (range, 11-104) days. Fifteen patients (18.1 %) had stage pT2 tumors, 22 (26.5 %) had RM of ≥3 mm, and 21 (25.3 %) had tumors of ≥3 cm in size. Thirteen patients (15.7 %) had LVI. Transanal excision was performed in 58 patients (69.9 %) and 25 patients (30.1 %) underwent EMR or ESD. The median follow-up was 61 months. The 5-year overall survival (OS), locoregional relapse-free survival (LRFS), and disease-free survival (DFS) rates for all patients were 94.9, 91.0, and 89.8 %, respectively. Multivariate analysis did not identify any significant factors for OS or LRFS, but the only significant factor affecting DFS was the pT stage (p = 0.027).. In patients with high-risk pT1 rectal cancer, adjuvant CCRT after local excision could be an effective alternative treatment instead of revision radical resection. However, patients with pT2 stage showed inferior DFS compared to pT1.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Disease-Free Survival; Endoscopy; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Postoperative Period; Prognosis; Rectal Neoplasms; Risk; Surgical Oncology; Treatment Outcome

To validate that a two-week short-course pre-operative radiotherapy regimen is feasible, safe, and effective for the management of elderly patients with locally advanced rectal cancer (LARC), we retrospectively analyzed 99 radiotherapy-naive patients ≥70 years of age with LARC. Patients received pelvic radiation therapy (3D-CRT 30Gy/10f/2w) followed by TME surgery; some patients received adjuvant chemotherapy. The primary endpoint was OS, while the secondary endpoints were DFS, safety and response rate. The median follow-up time was 5.1 years. The 5-year OS and DFS rates were 58.3% and 51.2%, respectively. The completion rate of radiotherapy (RT) was 99.0% (98 of 99). Grade 3 acute adverse events, which resulted from RT, occurred in only 1 patient (1.0%). In addition, no grade 4 acute adverse events induced by RT were observed. All 99 patients (100%) were able to undergo R0 surgical resection, and 68.6% of the patients received sphincter-sparing surgery. The rate of occurrence of clinically relevant post-operative complications was 12.1%. Three patients (3.0%) achieved pathologic complete responses, and forty-three patients (43.4%) achieved pathologic partial responses. The rates of T-downsizing and N-downstaging were 30.3% and 55.7%, respectively. Therefore, we believe that a two-week short-course pre-operative radiotherapy is feasible in elderly patients with resectable LARC.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemotherapy, Adjuvant; Combined Modality Therapy; Deoxycytidine; Dose Fractionation, Radiation; Female; Fluorouracil; Humans; Leucovorin; Male; Neoadjuvant Therapy; Organ Sparing Treatments; Organoplatinum Compounds; Oxaloacetates; Rectal Neoplasms; Retrospective Studies; Survival Analysis; Treatment Outcome

We report 2 cases of metastatic rectal cancer patients who received chemotherapy with FOLFOXIRI plus bevacizumab(Bev). Case 1: A 54-year-old woman diagnosed with advanced rectal cancer with synchronous liver metastasis underwent a laparoscopic low anterior resection. After the operation, she received FOLFOXIRI plus Bev treatment, and experienced Grade 4 adverse events, including dyspnea and ventricular fibrillation(Vf). After chemotherapy, no other metastasis was detected except a liver metastasis, and partial resection of the liver was performed. Histopathological evaluation revealed that the effect of the chemotherapy was Grade 1a. After liver resection, FOLFOXIRI plus Bev was administered, and a recurrence of the rectal cancer was not detected. Case 2: A 44-year-old woman was diagnosed with advanced rectal cancer with synchronous liver metastasis, distant lymph nodes metastasis, and vaginal invasion. First a colostomy was performed and FOLFOXIRI plus Bev treatment was administered. Grade 3 adverse events, including tremor, neuralgia, and anemia occurred, and chemotherapy was stopped for 3 months. Her adverse events were not under control when progression of the disease was detected, and her treatment was changed to another chemotherapy regimen.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Female; Fluorouracil; Hepatectomy; Humans; Leucovorin; Liver Neoplasms; Lymphatic Metastasis; Middle Aged; Organoplatinum Compounds; Rectal Neoplasms; Treatment Outcome

An 82-year-old man underwent anterior resection for rectal cancer in 2006. Local recurrence was diagnosed 5 years and 4 months after the operation. He could not undergo intensive chemotherapy because of his age and health status(a history of tubercular and pancytopenia due to chronic hepatitis C). sLV5FU2 chemotherapy was initiated. The CEA level decreased immediately after chemotherapy, and a complete response was observed on CT. After 18 courses, chemotherapy was discontinued. A complete response was detected for 1 year after the chemotherapy holiday began. For patients who experience difficulty tolerating intensive chemotherapy, good outcomes have been achieved even if relatively light regimens are used. For elderly patients or those with several complications, we suggest selecting a regimen based on the QOL.

Topics: Abdominal Neoplasms; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Leucovorin; Male; Rectal Neoplasms; Recurrence; Treatment Outcome

A 63-year-old man underwent low anterior resection for rectal cancer.A synchronous liver metastasis located in segment 8 was 12 cm in diameter and unresectable due to its proximity to the inferior vena cava(IVC).The postoperative pathological findings revealed a T3(SS), N0, M1(liver)Stage IV tumor, and wild type K-RAS was expressed.We chose FOLFIRI plus cetuximab(Cmab)for first-line chemotherapy.After 6 courses, we changed the molecular target drug from Cmab to bevacizumab( Bmab)because the liver metastasis remained unresectable.The patient had long-term stable disease(SD)for approximately 30 months with the FOLFIRI-based regimen.We then changed the regimen to mFOLFOX6 plus Bmab for second-line, Cmab for third-line, and trifluridine/tipiracil hydrochloride for fourth-line chemotherapy to treat progressive disease(PD).After treatment with these chemotherapies, the patient wished to continue treatment.We restarted FOLFIRI plus Bmab for fifth-line chemotherapy as his general condition was still good.Consequently, his tumor markers levels decreased with stabilization of the disease on CT scans, and he continued therapy for 6 months while maintaining a good quality of life.This case suggested that rechallenge with anti-cancer agents could be effective and improve the prognosis of colorectal cancer patients after using all key drugs.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Cetuximab; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Rectal Neoplasms; Tomography, X-Ray Computed; Treatment Outcome

The prognostic significance of perineural and/or lymphovascular invasion (PLVI) and its relationship with tumor regression grade (TRG) in patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (CRT) and surgery.. A total of 324 patients with LARC were treated with CRT and operated on between January 1992 and June 2007. Tumors were graded using a quantitative 5-grade TRG classification and the presence of PLVI was histologically studied.. At a median follow-up of 79.0 months (range 3-250 months), a total of 80 patients (24.7%) relapsed. The observed 5- and 10-year overall survival (OS) was 83.2 and 74.9 %, respectively. The 5- and 10-year disease-free survival (DFS) was 75.1 and 71.4%, respectively. A significant correlation was found between the TRG and survival (log rank, p < 0.001). The 10-year OS was 32.7% for grade 1, 63.8% for grade 2, 75.0% for grade 3, 90.4% for grade 3+, and 96.0%,for grade 4. The 10-year DFS was 31.8% for grade 1, 58.6% for grade 2, 70.4% for grade 3, 88.4% for grade 3+, and 97.1% for grade 4. In patients with PLVI, the TRG had no impact on survival. When excluding patients with PLVI, the TRG was an independent prognostic factor for OS and DFS.. The presence of PLVI is a more powerful prognostic factor than TRG in LARC patients treated with neoadjuvant CRT followed by surgery. PLVI denotes an aggressive phenotype, suggesting that these patients may benefit from adjuvant systemic therapy.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Chemoradiotherapy; Combined Modality Therapy; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Peripheral Nervous System Neoplasms; Postoperative Period; Prognosis; Rectal Neoplasms; Remission Induction; Survival Rate

Pathological response to chemotherapy without pelvic irradiation is not well defined in rectal cancer. This study aimed to evaluate the objective pathological response to preoperative chemotherapy without pelvic irradiation in middle or low locally advanced rectal cancer (LARC).. Between 2008 and 2013, 22 patients with middle or low LARC (T3/4 and/or N+ and circumferential resection margin < 2 mm) and synchronous metastatic disease or a contraindication to pelvic irradiation underwent rectal resection after preoperative chemotherapy. The pathological response of rectal tumour was analysed according to the Rödel tumour regression grading (TRG) system. Predictive factors of objective pathological response (TRG 2-4) were analysed.. All patients underwent rectal surgery after a median of six cycles of preoperative chemotherapy. Of these, 20 (91%) had sphincter saving surgery and an R0 resection. Twelve (55%) patients had an objective pathological response (TRG 2-4), including one complete response. Poor response (TRG 0-1) to chemotherapy was noted in 10 (45%) patients. In univariate analyses, none of the factors examined was found to be predictive of an objective pathological response to chemotherapy. At a median follow-up of 37.2 months, none of the 22 patients experienced local recurrence. Of the 19 patients with Stage IV rectal cancer, 15 (79%) had liver surgery with curative intent.. Preoperative chemotherapy without pelvic irradiation is associated with objective pathological response and adequate local control in selected patients with LARC. Further prospective controlled studies will address the question of whether it can be used as a valuable alternative to radiochemotherapy in LARC.

Topics: Adult; Anal Canal; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Chemoradiotherapy; Chemotherapy, Adjuvant; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Grading; Neoplasm Staging; Organ Sparing Treatments; Organoplatinum Compounds; Pelvis; Rectal Neoplasms; Rectum; Retrospective Studies

SMAD3, which is accumulated in the nucleus, transcriptionally regulates TGF-β target genes, playing a significant role in mediating the activities of TGF-β. In this study, we assessed the roles of TGF-β1, SMAD3, and phosphorylated SMAD3 expressions in patients with locally advanced rectal cancer following preoperative fluoropyrimidine-based chemoradiotherapy.. Using immunohistochemistry, we examined TGF-β1, SMAD3, and phosphorylated SMAD3 expressions in pre-chemoradiotherapy cancer tissues from 86 locally advanced rectal cancer patients. After chemoradiotherapy, 64 of 86 (74.4 %) locally advanced rectal cancer patients were classified as responders (pathological tumor regression grades of 2-4).. A multivariate analysis showed that phosphorylated SMAD3 overexpression correlated to poor preoperative chemoradiotherapy responses (P = 0.015; OR 7.218; 95 % CI 1.479-35.229). Furthermore, a poor response (pathological tumor regression grades of 0-1) was an independent predictor of postoperative relapse (P = 0.021; OR 5.452; 95 % CI 1.286-23.113). Additionally, patients with phosphorylated SMAD3 overexpression were found to have a worse disease-free survival (P = 0.023).. Our data suggested that analyzing pre-chemoradiotherapy tumors for phosphorylated SMAD3 overexpression would assist physicians in identifying locally advanced rectal cancer patients who may have a poor response risk to preoperative fluoropyrimidine-based chemoradiotherapy.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Disease-Free Survival; Dose Fractionation, Radiation; Female; Fluorouracil; Humans; Immunohistochemistry; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Proteins; Neoplasm Recurrence, Local; Phosphorylation; Rectal Neoplasms; Smad3 Protein; Survival Rate; Transforming Growth Factor beta1

To document the efficacy of intraoperative radiotherapy (IORT) followed by adjuvant chemoradiation in the management of locally advanced rectal cancer.. A total of 148 patients with pT4N0/T1-4N+ rectal adenocarcinoma were enrolled. Seventy-seven patients received total mesorectal excision surgery followed by adjuvant chemoradiation alone, 71 patients received total mesorectal excision surgery followed by IORT (range, 10 to 20 Gy) and adjuvant chemoradiation.. The 5-year local control (LC) and disease-free survival were 79.2% versus 89.7% (P=0.032), 58.5% versus 69.0% (P=0.049) for external-beam radiation (EBRT) and IORT+EBRT groups, respectively. Multivariate analysis revealed that adjuvant IORT has a trend toward improvement of LC (P=0.079); 5 (3%) patients (EBRT n=2; IORT n=3) experienced incomplete intestinal obstruction and 3 patients had chronic diarrhea. There was no clinically relevant neuropathy or sacral osteoradionecrosis. Hydronephrosis occurred in 13 patients (EBRT n=8; IORT+EBRT n=5), 8 of whom had documented concomitant disease recurrence.. For patients with locally advanced rectal cancer, higher radiation dose may contribute to the improvement of both LC and disease-free survival, without significantly increasing the incidence of acute and long-term complications compared with adjuvant chemoradiotherapy alone.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Cisplatin; Disease-Free Survival; Female; Fluorouracil; Humans; Intraoperative Care; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Organoplatinum Compounds; Oxaliplatin; Radiotherapy Dosage; Radiotherapy, Adjuvant; Rectal Neoplasms; Rectum

Preoperative chemoradiotherapy followed by total mesorectal excision (TME) is the standard treatment for stage III lower rectal cancer worldwide. However, in Japan, the standard treatment is TME with lateral pelvic lymph node dissection (LPLD) followed by adjuvant chemotherapy. We examined the safety and efficacy of adjuvant therapy with oxaliplatin, leucovorin, and 5-fluorouracil (modified FOLFOX6) after TME with LPLD.. This retrospective study included 33 patients who received modified FOLFOX6 after TME with LPLD for stage III lower rectal cancer.. The overall completion rate of 12 cycles of adjuvant modified FOLFOX6 was 76%. Grade 3 or 4 neutropenia was observed in eight patients (24%). Sensory neuropathy was observed in 32 patients (97%) with 4 (12%) having a grade 3 event. The disease-free survival (DFS) rate was 45% at 3 years.. Adjuvant modified FOLFOX6 was feasible in patients with stage III lower rectal cancer after TME with LPLD.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Lymph Node Excision; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms; Retrospective Studies

In recent decades, the management of rectal cancer has been significantly improved by optimizing the surgical treatment with the total mesorectal excision and the development of neoadjuvant radiotherapy with or without chemotherapy. In this study, we investigated the impact of changes in practice over a period of 15 years in an expert centre.. A monocentric study was conducted retrospectively on cT3-resectable T4 patients who received chemoradiotherapy for a locally advanced rectal adenocarcinoma between 1993 and 2008. We studied sphincter preservation, pathological complete response (ypT0), survival, and toxicities by different concomitant chemotherapy and treatment period.. Among the 179 patients who had a chemoradiotherapy, 56.4% were received concomitant 5-fluoro-uracil-leucovorin, 28.5% with concomitant capecitabine, and 15.1% with concomitant oxaliplatin and capecitabine. The average dose of radiotherapy was 45 Gy (25×1.8 Gy). Five-year disease-free survival was 74.3% and overall survival 68.8%. The rate of local recurrence and distant metastases were 6.1 and 23.6%. In multivariate analysis, concomitant chemotherapy oxaliplatin and capecitabine improved the pathological complete response rate (ypT0; capecitabine: 6%, 5-fluoro-uracil-leucovorin: 10.3%, capecitabine-oxaliplatin: 22.2%), but not significantly (P=0.12) and with more toxicities, and treatment interruptions. Sphincter preservation rate was not improved significantly during the study period (1993-2004 vs. 2005-2008), but disease-free survival improved from 72.2% up to 87.5% (P=0.03).. Our results are consistent with those published in the literature. Concomitant chemotherapy with 5-fluoro-uracil or capecitabine remains the standard scheme. Upfront chemotherapy, before chemoradiotherapy, should be investigated with regard to the predominance of metastasis.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Anal Canal; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemoradiotherapy, Adjuvant; Deoxycytidine; Disease-Free Survival; Female; Fluorouracil; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Neoplasms, Second Primary; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms; Retrospective Studies; Treatment Outcome

Patients with advanced and incurable colorectal cancer have a very poor prognosis. Curative-intent resection was performed in 70%-90% of cases in reported series of colorectal cancer, sometimes after neoadjuvant chemotherapy and radiotherapy. The remaining 10%-30% of patients are treated with palliative intent, where treatment is aimed at relieving disease-related symptoms and improving quality of life. The provision of palliative care for these patients is complicated and outcomes are often disappointing. Although there are many available options including a variety of surgical and nonsurgical interventions, the best management remains controversial. Transarterial chemoembolization with irinotecan-loaded drug-eluting beads (DEBIRI) is an effective, minimally invasive procedure performed by interventional radiologists that allows intra-arterial drug delivery to stop vascular feeding and exert local cytotoxic effects. We here report on a patient treated with DEBIRI followed by systemic chemotherapy with the FOLFOX regimen for locally advanced, inoperable colorectal cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemoembolization, Therapeutic; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Mesenteric Artery, Inferior; Microspheres; Middle Aged; Organoplatinum Compounds; Rectal Neoplasms; Treatment Outcome; Tumor Burden

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Administration Schedule; Europe; Fluorouracil; Humans; Leucovorin; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Peripheral Nervous System Diseases; Randomized Controlled Trials as Topic; Rectal Neoplasms; Sensory Receptor Cells; Treatment Outcome; United States

The maintenance of full bladder is important to reduce radiation-induced toxicities and maintain the therapeutic consistency in locally advanced rectal cancer patients who underwent radiotherapy (RT). So, the aim of this study was to evaluate the effectiveness of protocol-based full bladder maintenance by assessing bladder volume variation using an ultrasound bladder scanner to maintain bladder volume.. From March 2011 to May 2011, twenty consecutive rectal cancer patients receiving external beam RT participated in this prospective study. Protocol-based full bladder maintenance consisted of education, training and continuous biofeedback by measuring bladder volume. Bladder volume was measured by bladder scan immediately before simulation CT scan and before each treatment three times weekly during the RT period. The relative bladder volume change was calculated. Intra-patient bladder volume variations were quantified using interquartile range (IQR) of relative bladder volume change in each patient. We compared intra-patient bladder volume variations obtained (n=20) with data from our previous study patients (n=20) performing self-controlled maintenance without protocol.. Bladder volumes measured by bladder scan highly correlated with those on simulation CT scan (R=0.87, p<0.001). Patients from this study showed lower median IQR of relative bladder volume change compared to patients of self-controlled maintenance from our previous study, although it was not statistically significant (median 32.56% vs. 42.19%, p=0.058). Upon logistic regression, the IQR of relative bladder volume change was significantly related to protocol-based maintenance [relative risk 1.045, 95% confidence intervals (CI) 1.004-1.087, p=0.033]. Protocol-based maintenance included significantly more patients with an IQR of relative bladder volume change less than 37% than self-controlled maintenance (p=0.025).. Our findings show that bladder volume could be maintained more consistently during RT by protocol-based management using a bladder scan.

Topics: Adult; Aged; Antineoplastic Agents; Female; Fluorouracil; Gamma Rays; Humans; Leucovorin; Logistic Models; Male; Middle Aged; Prospective Studies; Rectal Neoplasms; Tomography, X-Ray Computed; Ultrasonography; Urinary Bladder; Urography

We present the case of a 62-year-old-man with moderately differentiated adenocarcinoma of the rectum. This patient underwent neoadjuvant chemoradiation and surgical resection followed by adjuvant chemotherapy. After completing therapy, this patient had 2 instances of CEA elevation, both of which preceded the discovery of recurrent disease. While on treatment for these recurrences, CA 19-9 increased rapidly to 4,405. This CA 19-9 elevation persisted for approximately 4 months in the absence of clinical, radiographic or additional serologic evidence of progressive disease before returning to baseline. Shortly after this tumor marker normalized, a small area of locally recurrent disease was discovered. This case highlights the utility and pitfalls of colorectal cancer disease monitoring with CEA and CA 19-9. The differential diagnosis of CA 19-9 elevation is discussed in this report.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; CA-19-9 Antigen; Carcinoembryonic Antigen; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Radiosurgery; Rectal Neoplasms

The aim of this study is to evaluate the effect of neoadjuvant chemoradiotherapy in stage IV rectal cancer.. Primary rectal cancer patients with synchronous distant metastases between September 2001 and August 2011 were enrolled. Of 86 patients, 40 patients underwent neoadjuvant chemoradiotherapy (RTX group) and the remaining 46 patients underwent postoperative systemic chemotherapy without radiotherapy (NRTX group). Sharp mesorectal excision according to tumor location was performed. Oncologic outcomes were compared.. The lower tumor location was more common in RTX group than NRTX group (60.0 vs. 28.3%, P = 0.003). Clinical T and N status and American Society of Anesthesiologist (ASA) score were similar in both groups. The incidence of pathologic LN metastases in the NRTX group was 93.5% compared with 70.0% in RTX group (P = 0.007). Pattern of distant metastasis was similar between groups. However, metastatectomy was frequently performed in RTX group than NRTX group (57.5 vs. 30.4%, P = 0.020). There was no statistical difference in local recurrence rate between groups (10.0% in RTX vs. 15.2% in NRTX, P = 0.470). The median PFS was similar in both groups (12.00 months in RTX vs. 12.00 months in NRTX, P = 0.768). The median OS between groups was also not different (24.00 months in RTX vs. 27.00 months in NRT, P = 0.510).. Neoadjuvant chemoradiotherapy may not affect local control and overall survival in locally advanced rectal cancer with distant metastasis.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Capecitabine; Chemoradiotherapy, Adjuvant; Chemotherapy, Adjuvant; Disease-Free Survival; Dose Fractionation, Radiation; Female; Fluorouracil; Humans; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Organoplatinum Compounds; Rectal Neoplasms; Survival Rate; Treatment Outcome

We report a case of radical resection of rectal cancer with multiple liver and lung metastases after preoperative chemotherapy. A 54-year-old woman presented with abdominal pain and loss of body weight due to rectal cancer with multiple liver and lung metastases. Therefore, the patient received 14 courses of bevacizumab+mFOLFOX6, and 7 courses of panitumumab+FOLFIRI. After the chemotherapy, the size of the distant metastases reduced by 62% on computed tomography, according to RECIST. Due to the reduction in size, a conversion surgery was attempted. First, an abdominal operation with laparoscopy was performed, and 2 months later an operation to resect the lung metastases via thoracoscopy was performed. Currently, 3 months after surgery, the patient is alive, without recurrence.

Topics: Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Middle Aged; Organoplatinum Compounds; Panitumumab; Rectal Neoplasms

The study analyzed and compared the long term outcome in locally advanced rectal cancer treated with preoperative and postoperative concurrent chemoradiation (CCRT).. A retrospective review of 105 patients with stage T3-T4 or regional lymph node positive adenocarcinoma of rectum treated with preoperative or postoperative CCRT at Ramathibodi Hospital during 2005 to 2010 was performed. The results of treatment were reported with 5-year overall survival (OS), 5- year locoregional recurrence free survival (LRFS), and toxicity according to preoperative versus postoperative concurrent chemoradiation (CCRT) groups.. Among 105 patients, 34 (32%) were treated with preoperative CCRT and 71 (68%) with postoperative CCRT. At the median follow-up time of 50.5 months (range 2-114 months), five-year OS and LRFS of all patients were 87% and 91.6%, respectively. The study found no difference in 5-year OS (81.7% vs 89.2 %) or LRFS (83.4% vs 95.1%) between preoperative versus postoperative CCRT. Seven cases of loco-regional recurrence were diagnosed, 4 (11.8%) after preoperative CCRT and 3 (4.2%) after postoperative CCRT. The recurrent sites were anastomosis in all patients. There was no significant factor associated with outcome after univariate and multivariate testing. Grade 3 or 4 acute and late complications were low in both preoperative and postoperative CCRT groups.. Locally advanced rectum cancer patients experience good results with surgery and adjuvant concurrent chemoradiation.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemoradiotherapy; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Postoperative Period; Preoperative Period; Prognosis; Rectal Neoplasms; Retrospective Studies; Schools, Medical; Survival Rate; Thailand; Time Factors

A 71-year-old man with predialysis terminal renal insufficiency experienced peritoneal dissemination 1.5 years after low anterior resection for advanced rectal cancer. He received FOLFIRI therapy (70% dose); he achieved partial response (PR) under computed tomography and stable disease (SD) was maintained over a long term. Although Grade 3 myelosuppression was occasionally noted, he was treated with FOLFIRI for 2 years without other severe complications and without requiring the initiation of hemodialysis. After the initiation of hemodialysis, FOLFIRI treatment was continued for 1 year until progressive disease (PD). He received mFOLFOX6 as second-line therapy for 6 months, followed by LV-5-FU and a molecular targeting agent. These treatments prolonged his survival for 1 year and 8 months. FOLFIRI can be administered as an effective first-line therapy even for patients with predialysis terminal renal impairment without major renal damage. FOLFOX and molecular targeting agents should be made available and prolonged survival can be expected for advanced colorectal cancer patients with terminal renal disease after the initiation of hemodialysis.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Dialysis; Fatal Outcome; Fluorouracil; Humans; Leucovorin; Male; Organoplatinum Compounds; Rectal Neoplasms; Recurrence; Renal Insufficiency, Chronic; Time Factors

Reports of conversion in cases of locally advanced colorectal cancer have been increasing. Here, we present 2 cases in which curative resection of locally advanced rectal cancer accompanied by intestinal obstruction was achieved after establishing a stoma and administering chemotherapy. The first case was of a 46-year-old male patient diagnosed with upper rectal cancer and intestinal obstruction. Because of a high level of retroperitoneal invasion, after establishing a sigmoid colostomy, 13 courses of mFOLFOX6 plus Pmab were administered. Around 6 months after the initial surgery, low anterior resection for rectal cancer and surgery to close the stoma were performed. Fourteen days after curative resection, the patient was discharged from the hospital. The second case was of a 66-year-old male patient with a circumferential tumor extending from Rs to R, accompanied by right ureter infiltration and sub-intestinal obstruction. After establishing a sigmoid colostomy, 11 courses of mFOLFOX6 plus Pmab were administered. Five months after the initial surgery, anterior resection of the rectum and surgery to close the stoma were performed. Twenty days after curative resection, the patient was released from the hospital. No recurrences have been detected in either case.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Rectal Neoplasms; Sigmoid Neoplasms; Surgical Stomas

A 60-year-old man underwent laparoscopic total proctocolectomy with ileostomy for advanced ulcerative colitis-associated rectal cancer. The final diagnosis was advanced cancer pT3, pN2 and M0 (pStage Ⅲb). Adjuvant therapy with XELOX was performed. However, abdominal CT revealed a liver metastasis and lymph node metastases in the pelvis 6 months after surgery. The patient was treated with FOLFIRI plus bevacizumab. After 20 courses of chemotherapy, the patient was considered to have experienced a clinical CR, which has been maintained for 3 years 5 months.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colitis, Ulcerative; Combined Modality Therapy; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Rectal Neoplasms; Recurrence; Remission Induction

A woman in her 60s showed positive results on a fecal occult blood test and consulted her doctor. Early-stage cancer of the lower rectum was diagnosed, and a transanal local excision was performed. Histopathological examination revealed that the depth of submucosal invasion was ≧1,000 mm, and the submucosal invasive part of the tumor was a poorly differentiated adenocarcinoma. Therefore, she was referred to our hospital for additional resection. Intersphincteric resection was performed 11 months after the initial operation. The cancer stage was T1N0M0, Stage Ⅰ(UICC 7th edition), and the cancer did not recur. The patient visited our hospital again, 78 months after the additional resection, because of left hip-joint pain. Positron-emission tomography revealed fluorodeoxyglucose uptake in the left acetabulum, para-aortic lymph nodes, and left external iliac lymph nodes; these findings indicated recurrence of the rectal cancer. The patient received radiation therapy (57 Gy) and FOLFIRI; bevacizumab was added from the third course onward. The therapy reduced the size of the tumor recurrence in the bone. This was a rare case of rectal cancer with submucosal invasion that showed recurrence in the bone and lymph nodes 78 months after the additional resection.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Bone Neoplasms; Camptothecin; Chemoradiotherapy; Female; Fluorouracil; Humans; Intestinal Mucosa; Leucovorin; Lymphatic Metastasis; Neoplasm Invasiveness; Neoplasm Staging; Rectal Neoplasms; Recurrence; Time Factors

A 61-year-old woman presented with the chief complaint of melena. She was diagnosed with rectal cancer via colonoscopy. Computed tomography (CT) revealed a rectal cancer with wall thickening, accompanied by several regional lymph node metastases with no distant metastasis. The tumor stage was cT3, cN2a, cM0 according to the TNM Classification of Malignant Tumors (7th Edition, UICC). Preoperative chemoradiotherapy (CRT) (UFT 400 mg/day tegafur-uracil and 75 mg/day Leucovorin; 1.8 Gy in 25 fractions, total 45 Gy) was administered. Eight weeks after CRT, laparoscopy-assisted low anterior resection was performed. A pathological examination revealed that both the primary site and regional lymph nodes had no residual cancer cells, and a diagnosis of pathological complete response was made. The patient has been disease-free for 4 years since the operation. We report a case of rectal cancer that was successfully treated via preoperative CRT. This case may aid the development of a standard therapy for advanced rectal cancer.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Female; Humans; Leucovorin; Middle Aged; Neoplasm Staging; Rectal Neoplasms; Remission Induction; Tegafur; Uracil

We describe a case of perforated rectal cancer that became curatively resectable after FOLFOX4 chemotherapy. An 81- year-old woman was transferred to our hospital with a diagnosis of bowel perforation. She underwent emergency transverse colostomy, peritoneal lavage, and the insertion of indwelling drainage tubes, because the perforated rectal cancer was considered unresectable. After recuperation, she received chemotherapy consisting of FOLFOX4 and bevacizumab. Owing to a good response to the treatment after 4 months, rectal resection was achieved curatively. Wound dehiscence occurred as a postoperative complication. The patient chose not to receive adjuvant chemotherapy. Currently, she has been alive for more than 1 year 3 months after resection without recurrence.

Topics: Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colostomy; Combined Modality Therapy; Female; Fluorouracil; Humans; Intestinal Perforation; Leucovorin; Organoplatinum Compounds; Rectal Neoplasms; Treatment Outcome

A patient in his 70s was diagnosed with rectal cancer (pT3, pN1, cM0, and pStage IIIa) for which he underwent low anterior resection of the rectum and received adjuvant therapy with UFT/LV. Multiple liver, lung, and para-aortic lymph node metastases were detected after 6 months, and the patient then received a total of 24 courses of FOLFOX4 plus bevacizumab instead of UFT/LV. The liver and para-aortic lymph node metastases showed a complete response (CR), and the lung metastases markedly diminished. Therefore, the patient completed the FOLFOX4 plus bevacizumab chemotherapy regimen. After 2 years, a recurrence of the initial liver metastases was detected. A CR on radiological imaging does not correspond to a pathological CR. Therefore, a careful follow-upis required even when a CR on radiological imaging is achieved.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Aorta; Bevacizumab; Chemotherapy, Adjuvant; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Organoplatinum Compounds; Rectal Neoplasms; Recurrence

The efficacy and safety of neoadjuvant chemotherapy in patients with highly advanced rectal cancer for whom radical surgery was considered difficult were evaluated.. From June 2007 to February 2011, 10 advanced lower rectal cancer patients with factors contraindicative of curative surgery with total mesenteric excision were eligible for this study. Neoadjuvant chemotherapy consisting of modified OPTIMOX1 (mFOLFOX6 and sLV5FU2 alternating administration) plus bevacizumab was administered.. Adverse events seen with chemotherapy consisted of grade 2 leukopenia in 1 patient, but there were no cases of delayed administration or dosage reduction due to grade 2 neurotoxicity. The surgical procedures were anus-preserving resection in 8 patients, total pelvic exenteration in 1 patient, and posterior pelvic exenteration in 1 patient. A positive radial margin was confirmed in 3 patients, but radical surgery was performed, histologically as well, in the other patients. Upon comparing the clinical and postoperative histological stages, primary tumor and node downstaging was achieved in 20.0% and 70.0% of the patients, respectively.. These findings suggest the potential utility of neoadjuvant chemotherapy consisting of modified OPTIMOX1 plus bevacizumab prior to permitting radical resection or anus-preserving surgery in patients with highly advanced rectal cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Cohort Studies; Digestive System Surgical Procedures; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaliplatin; Prospective Studies; Rectal Neoplasms; Rectum; Treatment Outcome

The aim of this study was to assess the prognostic value of metastatic lymph node (LN) ratio (MLNR) in stage III rectal cancer and whether this prognostic value remains significant when <12 LNs are retrieved.. This prospective study included 115 patients with stage III rectal cancer from 2006 to 2010. All patients underwent neoadjuvant long-course chemoradiation, curative resection, and postoperative adjuvant therapy (5-fluorouracil and leucovorin). Data collected included demographics, tumor pathology, tumor-node-metastasis staging, number of LNs retrieved, MLNR, recurrence, and mortality.. The mean number of examined LNs was 12.1, and the mean number of metastatic LNs was 3.5 (range, 1 to 19). The mean MLNR was .37 (range, 0 to 1.00). The mean duration of follow-up was 37 months (range, 24 to 63). Forty patients died during the follow-up period (overall mortality, 34.8%), only 31 because of cancer (cancer-specific mortality, 27%). Univariate analysis revealed that ypN stage, lymphovascular invasion, and follow-up duration were significantly associated with increased recurrence and decreased survival. Number of positive nodes and ypT stage significantly affected recurrence, with no effect on overall survival. Multivariate analysis proved that MLNR was the only independent risk factor for both mortality and recurrence. Prognostic capability was not affected by having <12 nodes retrieved. The best sensitivity and specificity of MLNR as a prognostic factor for both tumor recurrence and overall survival were achieved at a cutoff value of .375.. MLNR is an independent prognostic factor for recurrence and survival after the resection of stage III rectal cancer, with high sensitivity and specificity in patients who received neoadjuvant chemoradiation and postoperative chemotherapy. The total number of LN retrieved did not affect the prognostic value of MLNR even if <12.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Agents; Biomarkers, Tumor; Chemoradiotherapy; Colonoscopy; Female; Fluorouracil; Humans; Leucovorin; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Prospective Studies; Rectal Neoplasms; Survival Rate; Tomography, X-Ray Computed

It has been previously reported that a short FOLFOX-4 induction significantly improves pathologic complete response in locally advanced rectal cancer (LARC) patients treated with preoperative chemoradiation (CRT). In a larger and updated patient series, we analyzed FOLFOX-4 efficacy in terms of sphincter preservation and long-term outcomes.. From January 1995 to December 2010, 335 LARC patients were treated with preoperative chemoradiation (4500-5040 cGy). Starting in May 2001, 207 consecutive patients additionally received induction FOLFOX-4. Surgery was performed 6 weeks (range 3-12 weeks) after chemoradiation.. Incidence of total tumor (63 vs. 54 %, p = 0.02) and nodal downstaging (60 vs. 43 %, p = 0.002) was significantly increased by induction FOLFOX-4. In an analysis of tumors located below 5 cm from the anal verge (n = 114, 34 %), sphincter preservation was feasible in 30 % in the FOLFOX-4 versus 13 % in the upfront CRT group (p = 0.04). Median follow-up time for the entire cohort of patients was 72.6 months (range 4-205 months). FOLFOX-4 was not associated with superior locoregional control (HR 0.88, p = 0.78), disease-free survival (HR 0.83, p = 0.55), distant metastases-free survival (HR 0.94, p = 0.81), or cancer-specific survival (HR 0.70, p = 0.15).. Short-intense induction FOLFOX-4 significantly improves downstaging and sphincter preservation in low rectal tumors. Long-term outcomes were not improved in the FOLFOX-4 group of patients.

Topics: Adult; Aged; Aged, 80 and over; Anal Canal; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Combined Modality Therapy; Disease-Free Survival; Feasibility Studies; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organ Sparing Treatments; Organoplatinum Compounds; Rectal Neoplasms; Treatment Outcome

Complete pathological response occurs in 10-20% of patients with rectal cancer who are treated with neoadjuvant chemoradiation therapy prior to pelvic surgery. The possibility that complete pathological response of rectal cancer can also occur with neoadjuvant chemotherapy alone (without radiation) is an intriguing hypothesis.. A 66-year old man presented an adenocarcinoma of the rectum with nine liver metastases (T3N1M1). He was included in a reverse treatment, aiming at first downsizing the liver metastases by chemotherapy, and subsequently performing the liver surgery prior to the rectum resection. The neoadjuvant chemotherapy consisted in a combination of oxaliplatin, 5-FU, irinotecan, leucovorin and bevacizumab (OCFL-B). After a right portal embolization, an extended right liver lobectomy was performed. On the final histopathological analysis, all lesions were fibrotic, devoid of any viable cancer cells. One month after liver surgery, the rectoscopic examination showed a near-total response of the primary rectal adenocarcinoma, which convinced the colorectal surgeon to perform the low anterior resection without preoperative radiation therapy. Macroscopically, a fibrous scar was observed at the level of the previously documented tumour, and the histological examination of the surgical specimen did not reveal any malignant cells in the rectal wall as well as in the mesorectum. All 15 resected lymph nodes were free of tumour, and the final tumour stage was ypT0N0M0. Clinical outcome was excellent, and the patient is currently alive 5 years after the first surgery without evidence of recurrence.. The presented patient with stage IV rectal cancer and liver metastases was in a unique situation linked to its inclusion in a reversed treatment and the use of neoadjuvant chemotherapy alone. The observed achievement of a complete pathological response after chemotherapy should promote the design of prospective randomized studies to evaluate the benefits of chemotherapy alone in patients with stages II-III rectal adenocarcinoma (without metastasis).

Topics: Adenocarcinoma; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Chemotherapy, Adjuvant; Fluorouracil; Hepatectomy; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Male; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms; Rectum

A pathologic complete response (pCR) can be observed in up to 25% of patients after preoperative chemoradiotherapy for rectal cancer and is associated with an improved long-term prognosis. However, few data are available regarding the effect of pCR on postoperative morbidity. This study aimed to assess the impact of the pCR on postoperative outcomes after laparoscopic total mesorectal excision (TME).. A prospectively maintained database (2006-2011) was reviewed for all consecutive patients (n = 143) undergoing laparoscopic TME for mid or low rectal cancer after neoadjuvant chemoradiotherapy. Postoperative data were compared for pCR-group and non-pCR-group. A pCR was defined as the absence of gross and microscopic tumor in the specimen, irrespective of the nodal status (ypT0).. Thirty-three patients (23%) had a pCR. Median operating time was greatly shorter in the pCR-group (230 minutes, 180-360), compared with the non-pCR-group (240 minutes, 130-420, P = .02). Lymph node involvement was noted for 12% of the patients in the pCR-group and 33% of the patients in the non-pCR-group (P = .91). Clavien Dindo grade 3 and 4 complications (6% vs 22%, P = .04), infection related morbidity (47% vs 76%, P = .04), and clinical anastomotic leakage rates (9% vs 29%, P = .02) were lesser in the pCR group compared with the non-pCR group. Mean duration of hospital stay was lesser in the pCR-group (9 vs 12 days, P = .01).. This study showed that Clavien Dindo grade 3 and 4 complications, including anastomosis leakage, and infection related complications rates were lesser in patients with pathologic complete response after RCT and laparoscopic TME for rectal cancer.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Female; Fluorouracil; Humans; Laparoscopy; Length of Stay; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Operative Time; Organoplatinum Compounds; Oxaliplatin; Postoperative Complications; Rectal Neoplasms; Rectum; Treatment Outcome

Abdominosacral resection may be the only curative procedure for locally advanced rectal cancer involving the presacral fascia or sacrum. Multimodal therapy might be necessary to prevent local and distant recurrence for such tumors. A 67-year-old man was diagnosed with locally advanced rectal cancer widely involving the right pelvic sidewall and presacral fascia near the S4/5 junction on the right posterolateral side. We performed laparoscopic abdominosacral resection (S4/5) with en bloc right lateral lymph node dissection and seminal vesicle resection to obtain a clear resection margin after systemic chemotherapy with mFOLFOX6 (oxaliplatin, leucovorin, and 5-fluorouracil) plus bevacizumab, followed by preoperative chemoradiotherapy. The total operative time was 660 min, and the estimated blood loss was 550 mL. The final pathological findings revealed no residual cancer cells (pathological complete response). Laparoscopic abdominosacral resection appears to be safe and feasible in selected patients.

Topics: Abdomen; Adenocarcinoma; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Chemoradiotherapy, Adjuvant; Chemotherapy, Adjuvant; Fluorouracil; Humans; Laparoscopy; Leucovorin; Male; Neoadjuvant Therapy; Organoplatinum Compounds; Rectal Neoplasms; Rectum; Sacrum

Carcinoembryonic antigen (CEA) is the most widely used tumor marker for colorectal cancer. This study aimed to investigate the role of CEA reduction ratio after preoperative chemoradiotherapy (CRT).. We enrolled 284 patients who underwent preoperative CRT followed by radical surgical resection. Patients were divided into 3 groups: serum CEA levels before CRT (pre-CRT CEA) less than 5 ng/mL (group 1); pre-CRT CEA of 5 ng/mL or more with CEA reduction ratio of 50% or more (group 2); and pre-CRT CEA of 5 ng/mL or more with CEA reduction ratio less than 50% (group 3).. The 5-year disease-free survival (DFS) rate was not different between groups 1 (71.8%) and 2 (69.4%) but was significantly lower in group 3 (49.5%). CEA group, lymph node status after CRT (ypN) stage, and histologic type were independent prognostic factors for DFS on multivariate analysis.. CEA reduction ratio might be an independent prognostic factor for DFS in rectal cancer patients treated with preoperative CRT and radical surgery.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoembryonic Antigen; Chemoradiotherapy, Adjuvant; Disease-Free Survival; Dose Fractionation, Radiation; Female; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Multivariate Analysis; Prognosis; Rectal Neoplasms; Rectum; Retrospective Studies; Tegafur; Treatment Outcome; Uracil

The purpose of this study was to assess the value of magnetic resonance imaging (MRI) and additional (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for tumor response to neoadjuvant chemotherapy (NAC) in patients with locally advanced rectal cancer (LARC).. Data on 40 patients with LARC, who were treated with NAC and underwent MRI and FDG-PET/CT before and after NAC, were analyzed retrospectively. Surgery was performed at a median of 6 weeks after NAC and the images were compared with the histological findings. The tumor regression grade 3/4 was classified as a responder.. Sixteen patients were pathological responders. Receiver operating characteristic (ROC) analysis revealed that MRI total volume after NAC (MRI-TV2) and ΔMRI-TV had the highest performance to assess responders (area under the ROC curve [AUC] 0.849 and AUC 0.853, respectively). The reduction rate of the maximum standardized uptake value (ΔSUVmax) was also an informative factor (AUC 0.719). There seems no added value of adding FDG-PET/CT to MRI-TV2 and ΔMRI-TV in assessment of NAC responders judging from changes in AUC (AUC of ΔSUVmax and MRI-TV2 was 0.844, and AUC of ΔSUVmax and ΔMRI-TV was 0.846).. MRI-TV2 and ΔMRI-TV were the most accurate factors to assess pathological response to NAC. Although ΔSUVmax by itself was also informative, the addition of FDG-PET/CT to MRI did not improve performance. Patients with LARC who were treated by induction chemotherapy should receive an MRI examination before and after NAC to assess treatment response. A more than 70 % volume reduction shown by MRI volumetry may justify the omission of subsequent radiotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Capecitabine; Chemotherapy, Adjuvant; Deoxycytidine; Female; Fluorodeoxyglucose F18; Fluorouracil; Humans; Leucovorin; Magnetic Resonance Imaging; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaloacetates; Positron-Emission Tomography; Radiopharmaceuticals; Rectal Neoplasms; Retrospective Studies; ROC Curve; Treatment Outcome

Pathological complete remission of advanced stage rectal adenocarcinoma by chemotherapy alone is rare. A case of advanced stage, low-lying rectal adenocarcinoma in which a complete response to treatment was obtained with mFOLFOX6 and panitumumab (Pmab) is reported.. A 53-year-old man was referred to Shiga University of Medical Science hospital Shiga, Japan, complaining of bloody stool. Gastrointestinal endoscopy was performed, and advanced stage rectal adenocarcinoma was diagnosed. Computed tomography (CT) revealed regional lymph node metastases in the mesorectum. Neoadjuvant chemotherapy (NAC) with mFOLFOX6 and Pmab was planned.Endoscopy following four courses of chemotherapy revealed that the rectal cancer had been markedly reduced, and the results of biopsies of the rectal tumor were negative for cancer. On CT, the mesorectal lymph node metastases had disappeared. Total intersphincteric resection (ISR) with a handsewn coloanal anastomosis was performed. Histological examination showed a complete response to mFOLFOX6 and Pmab in advanced stage rectal cancer.. The result seen in this case suggests that short-term NAC with mFOLFOX6 and Pmab was effective for low-lying rectal adenocarcinoma.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Organoplatinum Compounds; Panitumumab; Prognosis; Rectal Neoplasms; Remission Induction

Numerous molecular markers have been investigated as potential predictors of tumor responses to preoperative chemoradiotherapy (preCRT) for rectal cancer.. To develop a system in which biomarkers are used to predict the likelihood of a pathologic complete response (pCR) to preCRT.. This is a retrospective analysis of tumor specimens collected prior to preCRT from 81 patients who underwent curative resection for primary rectal adenocarcinoma between June 2008 and February 2012.. Using tissue microarrays and immunohistochemistry, expression levels of twelve candidate biomarkers (p53, p21, Bcl2, Bax, EGFR, Cox-2, MLH-1, MSH-2, Ku70, VEGF, TS, Ki-67) were evaluated in paraffin-embedded tumor samples collected before preCRT. The correlation between biomarker expression levels and the pathologic response to preCRT was assessed based on histopathological staging (pTNM) and tumor regression grade (TRG).. Expression levels of 4 biomarkers (p53, VEGF, p21, Ki67) correlated with pCR. Patients showing low expression of p53 and/or high expression of VEGF, p21, and Ki67 exhibited a significantly greater pCR rate. A scoring system devised so that one point was given for each biomarker whose expression level correlated with pCR (score range: 0-4) showed that 1 of 26 patients with scores of 0 to 1 achieved pCR, whereas 26 of 55 patients with scores of 2 to 4 achieved pCR (3.8% vs. 47.3%, p < 0.001). For prediction of pCR, the scoring system showed 96.3% sensitivity, 46.3% specificity, a 47.3% positive predictive value, and a 96.2% negative predictive value.. Immunohistochemistry has limitations related to reproducibility and the ability to provide quantitative information. In addition, this study lacks test and validation sets.. Expression levels of 4 biomarkers correlated with pCR after preCRT for rectal cancer. A scoring system based on levels of biomarker expression showed good sensitivity and negative predictive value for pCR.

Topics: Adenocarcinoma; Adult; Aged; Biomarkers, Tumor; Biopsy; Chemoradiotherapy; Combined Modality Therapy; Fluorouracil; Humans; Leucovorin; Lymphatic Metastasis; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Polymerase Chain Reaction; Predictive Value of Tests; Radiotherapy Dosage; Rectal Neoplasms; Retrospective Studies; Sigmoidoscopy; Treatment Outcome

Neoadjuvant chemoradiotherapy is commonly used to improve the local control and resectability of locally advanced rectal cancer, with surgery performed after an interval of a number of weeks. We have been conducting a clinical trial of preoperative chemoradiotherapy in combination with regional hyperthermia (hyperthermo-chemoradiation therapy; HCRT) for locally advanced rectal cancer. In the current study we assessed the effect of a longer (>10 weeks) interval after neoadjuvant HCRT on pathological response, oncological outcome and especially on apoptosis, proliferation and p53 expression in patients with rectal cancer. Forty-eight patients with proven rectal adenocarcinoma who underwent HCRT followed by surgery were identified for inclusion in this study. Patients were divided into two groups according to the interval between HCRT and surgery, ≤ 10 weeks (short-interval group) and >10 weeks (long-interval group). Patients in the long-interval group had a significantly higher rate of pathological complete response (pCR) (43.5% vs. 16.0%) than patients of the short-interval group. Patients of the long-interval group had a significantly higher rate of down-staging of T-stage (78.3% vs. 36.0%) and relatively higher rate of that of N-stage (52.2% vs. 36.0%) than patients of the short-interval group. Furthermore, apoptosis in the long-interval group was relatively higher compared to that of the short-interval group, without a significant difference in the Ki-67 proliferative index and expression of p53 in the primary tumor. In conclusion, we demonstrated that a longer interval after HCRT (>10 weeks) seemed to result in a better chance of a pCR, a result confirmed by the trends in tumor response markers, including apoptosis, proliferation and p53 expression.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Cell Proliferation; Chemoradiotherapy; Female; Fluorouracil; Humans; Hyperthermia, Induced; Immunoenzyme Techniques; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasm Staging; Rectal Neoplasms; Survival Rate; Treatment Outcome

Patients with locally advanced rectal cancer (LARC) have a dismal prognosis. We investigated outcomes and risk factors for locoregional recurrence (LRR) in patients treated with preoperative chemoradiotherapy (CRT), surgery and IOERT.. A total of 335 patients with LARC [⩾cT3 93% and/or cN+ 69%) were studied. In multivariate analyses, risk factors for LRR, IFLR and OFLR were assessed.. Median follow-up was 72.6 months (range, 4-205). In multivariate analysis distal margin distance ⩽10 mm [HR 2.46, p = 0.03], R1 resection [HR 5.06, p = 0.02], tumor regression grade 1-2 [HR 2.63, p = 0.05] and tumor grade 3 [HR 7.79, p < 0.001] were associated with an increased risk of LRR. A risk model was generated to determine a prognostic index for individual patients with LARC.. Overall results after multimodality treatment of LARC are promising. Classification of risk factors for LRR has contributed to propose a prognostic index that could allow us to guide risk-adapted tailored treatment.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Electrons; Female; Fluorouracil; Humans; Intraoperative Care; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Organoplatinum Compounds; Prognosis; Radiotherapy, Conformal; Rectal Neoplasms; Tegafur

Until recently, no studies have prospectively evaluated bowel function after sphincter-preserving surgery for rectal cancer with the use of a validated bowel function scoring system.. The aim of this study was to investigate possible risk factors for altered bowel function after sphincter-preserving surgery.. This was a prospective study.. The study was conducted between January 2006 and May 2012 at the authors' institution.. Patients who underwent sphincter-preserving rectal cancer surgery were recruited.. Bowel function was assessed 1 day before (baseline) and at 1 year after sphincter-preserving surgery or temporary ileostomy takedown with the use of the Memorial Sloan Kettering Cancer Center questionnaire. Multivariable analysis was performed to identify the factors associated with altered bowel function after surgery.. Overall, 266 patients were eligible for the analysis. The tumor was located in the upper, middle, and lower rectum in 68 (25.5%), 113 (42.5%), and 85 (32.0%) patients. Intersphincteric resection and temporary ileostomy were performed in 18 (6.8%) and 129 (48.5%) patients. The mean Memorial Sloan Kettering Cancer Center score was 64.5 ± 7.6 at 1 year after sphincter-preserving surgery or temporary ileostomy takedown. The Memorial Sloan Kettering Cancer Center score decreased in 163/266 patients (61.3%) between baseline and 1 year after surgery. Tumor location (p = 0.01), operative method (p = 0.03), anastomotic type (p = 0.01), and temporary ileostomy (p = 0.01) were associated with altered bowel function after sphincter-preserving surgery in univariate analyses. In multivariable analysis, only tumor location was independently associated with impaired bowel function after sphincter-preserving rectal cancer surgery.. This study was limited by its nonrandomized design and the lack of measurement before preoperative chemoradiotherapy.. We suggest that preoperative counseling should be implemented to inform patients of the risk of bowel dysfunction, especially in patients with lower rectal cancer, although this study cannot exclude the effect of chemoradiotherapy owing to the limitation of study.

Topics: Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Capecitabine; Chemoradiotherapy; Deoxycytidine; Fecal Incontinence; Female; Fluorouracil; Humans; Ileostomy; Irinotecan; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Postoperative Complications; Prospective Studies; Rectal Neoplasms; Risk Factors; Surveys and Questionnaires; Tomography, X-Ray Computed; Treatment Outcome

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Female; Fluorouracil; Humans; Leucovorin; Male; Neoadjuvant Therapy; Organoplatinum Compounds; Rectal Neoplasms

Colorectal cancer (CRC) is among the most common cancers worldwide, but marked epidemiological differences exist between Asian and non-Asian populations. Hence, a consensus meeting was held in Hong Kong in December 2012 to develop Asia-specific guidelines for the management of metastatic CRC (mCRC). A multidisciplinary expert panel, consisting of 23 participants from 10 Asian and 2 European countries, discussed current guidelines for colon or rectal cancer and developed recommendations for adapting these guidelines to Asian clinical practice. Participants agreed that mCRC management in Asia largely follows international guidelines, but they proposed a number of recommendations based on regional 'real-world' experience. In general, participants agreed that 5-fluorouracil (5-FU) infusion regimens in doublets can be substituted with UFT (capecitabine, tegafur-uracil) and S1 (tegafur, 5-chloro-2,4-dihydroxypyridine and oxonic acid), and that the monoclonal antibodies cetuximab and panitumumab are recommended for KRAS wild type tumors. For KRAS mutant tumors, bevacizumab is the preferred biological therapy. FOLFOX (folinic acid, 5-FU, and oxaliplatin) is preferred for initial therapy in Asian patients. The management of mCRC is evolving, and it must be emphasized that the recommendations presented here reflect current treatment practices and thus might change as more data become available.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Asia; Bevacizumab; Camptothecin; Capecitabine; Cetuximab; Colonic Neoplasms; Combined Modality Therapy; Deoxycytidine; Drug Combinations; ErbB Receptors; Fluorouracil; Guideline Adherence; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Magnetic Resonance Imaging; Metastasectomy; Neoplasm Staging; Organoplatinum Compounds; Oxaloacetates; Oxonic Acid; Panitumumab; Practice Guidelines as Topic; Proto-Oncogene Proteins; Proto-Oncogene Proteins p21(ras); ras Proteins; Rectal Neoplasms; Tegafur; Tomography, X-Ray Computed

Neoadjuvant chemoradiotherapy has been introduced in patients with surgically resected rectal cancer and reduced the local recurrence. Heterogeneity exists in rectal cancer, and we hypothesized that there are subclones resistant to chemoradiotherapy within the cancer mass. We performed DNA-targeted sequencing of pre- and post-treatment tumor tissues obtained from 20 rectal cancer patients who received chemoradiotherapy. The variant frequency of the mutant clones was compared between pre- and post-treatment samples of nine non-responder patients. RNA-targeted sequencing of 57 genes related to sensitivity to chemotherapy and radiotherapy was performed for the paired samples. Immunohistochemical analyses of p53 expression were also performed on the paired samples from the nine non-responder patients. DNA-sequencing detected frequent mutations of suppressor genes including TP53, APC and FBXW7 in the post-treatment samples of the nine non-responders. The frequency of TP53 mutations showed significant increases after chemoradiotherapy. RNA-targeted sequencing of 29 tumor tissues demonstrated that decreased expression of three genes and increased expression of four genes were detected in the post-treatment samples. Significantly increased expression of TP53 was observed in the post-treatment samples. Immunohistochemical staining for p53 revealed that increased p53 intensity scores were observed after chemoradiotherapy. These results suggest that the tumors with TP53 mutations tend to accumulate through chemoradiotherapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; DNA, Neoplasm; Humans; Immunohistochemistry; Leucovorin; Mutation; Neoadjuvant Therapy; Rectal Neoplasms; Retrospective Studies; Sequence Analysis, DNA; Tegafur; Tumor Suppressor Protein p53; Uracil

We aimed to evaluate early clinical and pathological results for treating locally advanced rectal cancer with bevacizumab and neoadjuvant concurrent chemoradiotherapy using the technique of prone-position volumetric modulated arc therapy and to compare the toxicity of volumetric modulated arc therapy with that of supine-position four-field box radiotherapy.. Twelve patients with stage IIA to IVA rectal adenocarcinoma, treated with neoadjuvant concurrent chemoradiotherapy (45 Gy in 25 fractions to the rectal tumor and pelvic lymphatics) and bevacizumab, were prospectively enrolled. Chemotherapy included FOLFOX (leucovorin, fluorouracil, and oxaliplatin) (n=11) and 5-fluorouracil (n=1). All patients received prone-position volumetric modulated arc therapy. A historical cohort treated with supine-position box radiotherapy, including six other patients treated with bevacizumab-based concurrent chemoradiotherapy in our hospital, was used for comparison. Setup errors, toxicities, and potential biomarkers were evaluated.. All patients completed neoadjuvant concurrent chemoradiotherapy and underwent total mesorectal excision. Four (33.3%) patients had pathological complete response. Significantly more grade 2 or 3 diarrhea was associated with the supine-box technique (5/6 versus 2/12, P=0.01). The magnitude of setup errors was similar between the supine-box and prone volumetric modulated arc therapy techniques. The estimated 2-year survival and 2-year failure-free survival rates were 100% and 72.9% in the prone volumetric modulated arc therapy group and 66.7% and 66.7% in the supine box group, respectively.. The early clinical outcome has been encouraging. Volumetric modulated arc therapy in prone-positioned patients was technically advantageous and reduced bowel toxicity.

Topics: Adenocarcinoma; Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Chemoradiotherapy; Cohort Studies; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Prognosis; Radiotherapy, Intensity-Modulated; Rectal Neoplasms; Remission Induction; Survival Rate

Leucovorin calcium, 5-fluorouracil, and oxaliplatin (FOLFOX) therapy is a standard chemotherapy regimen used to treat colorectal cancer. Peripheral nerve disorder and myelosuppression are frequently reported treatment-related adverse events. With modified FOLFOX6 (mFOLFOX6) therapy, adverse events of an altered mental state with reversible posterior leukoencephalopathy and hypoammonemia have been reported, while lactic acidosis is uncommon. We describe a case of mFOLFOX6 - induced lactic acidosis in a 64-year-old man with colorectal cancer who underwent pelvic exenteration following chemotherapy. Postoperative histopathological analysis revealed residual cancer. Following the commencement of mFOLFOX6 therapy, the patient experienced emesis, hiccupping, and an altered mental state. Laboratory testing revealed only severe lactic acidosis, while diagnostic imaging was unrevealing. All symptoms quickly improved upon the administration of intravenous infusion of sodium bicarbonate.

Topics: Acidosis, Lactic; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Rectal Neoplasms; Sigmoid Neoplasms

Herein, we present a case of advanced rectal cancer surgically resected after chemotherapy. A 65-year-old woman presented with anal pain, and rectal cancer extending beyond the anus was diagnosed. The primary tumor was a well-differentiated adenocarcinoma with a KRAS mutation. Computed tomography revealed cancer invasion into the vagina and sacral and coccygeal bones, and cancer metastases to the bilateral inguinal lymph nodes and the left lung. Sigmoid colostomy and subcutaneous venous port insertion were performed. The patient was treated with modified oxaliplatin, leucovorin, and 5- fluorouracil (FOLFOX6) plus bevacizumab. She showed a partial response according to the Response Evaluation Criteria in Solid Tumors after 13 courses of chemotherapy. The primary tumor was then resected via posterior pelvic exenteration, bilateral inguinal lymphadenectomy, and sacral/coccygeal resection. Histological examination of the resected specimens revealed moderately differentiated adenocarcinoma with vaginal invasion. Metastasis to a right inguinal lymph node was observed. The pathological stage was ypT4bN0M1b, ypStage IV according to the tumor-node-metastasis system of the eighth edition of the Japanese Classification of Colorectal Carcinoma. The pathological response grade of the tumor after chemotherapy was determined to be Grade 1b.

Topics: Adenocarcinoma; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Neoplasm Invasiveness; Organoplatinum Compounds; Rectal Neoplasms; Tomography, X-Ray Computed

A female patient in her 70s underwent an abdominoperineal resection and bilateral lymph node dissection for advanced lower rectal cancer. The patient did not receive neoadjuvant therapy. In the Japanese classification of colorectal carcinoma (8th Edition), the tumor was a moderately differentiated type 2 adenocarcinoma, and was 4.5 cm in size. Histologically, the tumor was considered to be Stage IIIb (T3N0M0). She received no adjuvant chemotherapy. After 39 months, pelvic computed tomography (CT ) revealed a 29 mm tumor in the right pelvic wall. The patient declined surgery for recurrence so radiotherapy was planned. First, chemotherapy with mFOLFOX6 was administered for 4 courses to reduce tumor size. Consequently, irradiation with carbon ions was given to the site of recurrence at a total dose of 74 GyE in 37 fractions. There were no severe complications. Carcinoembryonic antigen (CEA) level decreased to the lower limit of the normal range from a maximum of 4.9, and no progression of the recurrent tumor was detected on CT for approximately 4 years. Systemic chemotherapy followed by irradiation with carbon ions may be effective for recurrent rectal cancer.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Heavy Ion Radiotherapy; Humans; Leucovorin; Neoplasm Staging; Organoplatinum Compounds; Pelvic Neoplasms; Rectal Neoplasms; Recurrence

A-64-years-old woman with locally advanced rectal cancer, which had invaded the vagina, was referred to our hospital. She was administered neoadjuvant chemotherapy to reduce the tumor size. After 4 courses of chemotherapy consisting of folinic acid, fluorouracil, and oxaliplatin (mFOLFOX6), an enhanced computed tomography (CT) scan and magnetic resonance imaging (MRI) indicated marked tumor shrinkage. We performed a laparoscopically assisted low anterior resection, which included total mesorectal resection, resection of the vaginal posterior wall, and right lateral lymph node resection. The chemotherapy prevented us from having to create a permanent colostomy. The efficacy of the neoadjuvant chemotherapy was Grade 1b. We experienced a case of neoadjuvant chemotherapy followed by curative resection.

Topics: Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Laparoscopy; Leucovorin; Middle Aged; Neoadjuvant Therapy; Neoplasm Invasiveness; Organoplatinum Compounds; Rectal Neoplasms; Vagina

A 6 6-year-old woman with hematochezia was admitted to our hospital. A colonoscopy detected KRAS wild-type rectal cancer. An abdominal computed tomography (CT) scan revealed a liver metastasis, and invasion to the uterus was suspected. The patient underwent a laparotomy, and intraoperative cytology and peritoneal dissemination proved positive. The tumor had invaded the uterus. We administered chemotherapy consisting of 5-fluorouracil, Leucovorin, and oxaliplatin(mFOL FOX6)plus panitumumab. A CT scan and colonoscopy performed after 10 courses of chemotherapy indicated remarkable tumor regression. An abdominal CT scan did not detect any liver metastases, and we performed a laparoscopic low anterior resection. In the second operation, peritoneal dissemination and washing cytology were negative. The pathological diagnosis of the surgically resected specimen was ypStageII. The patient is recurrence-free 7 months after surgery.

Topics: Aged; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Fluorouracil; Humans; Laparoscopy; Leucovorin; Liver Neoplasms; Neoplasm Invasiveness; Neoplasm Staging; Organoplatinum Compounds; Panitumumab; Peritoneal Neoplasms; Rectal Neoplasms; Tomography, X-Ray Computed

We aimed to clarify the oncological significance of the number of lymph nodes in rectal cancers treated with preoperative chemoradiotherapy.. We studied 126 curatively operated patients with clinical T3-T4 and M0 rectal cancers. The number of lymph nodes and clinicopathological features were compared between the patients treated with surgery alone (OP group, n = 45) and those treated with preoperative chemoradiotherapy (50-50.4 Gy in 25-28 fractions with tegafur-uracil and leucovorin, CRT group, n = 81). Factors influencing lymph node count and its prognostic significance were analyzed.. The CRT group had significantly fewer lymph nodes than the OP group (12.4 vs. 21.1, P < 0.0001). High histological regression of rectal lesions was significantly correlated with decreased lymph node count in the CRT group. In the OP group, the 5-year cancer-specific survival rate of the patients with 12 or more lymph nodes was significantly better than those with fewer than 12 lymph nodes (75.1% vs. 33.3%, P = 0.02); in the CRT group, on the other hand, these survival rates did not differ (84.5% vs. 77.5%, P = 0.6).. The number of lymph nodes in rectal cancer was correlated with the response of primary rectal lesions to chemoradiotherapy, and was not associated with patient survival.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Disease Progression; Disease-Free Survival; Dose Fractionation, Radiation; Female; Humans; Kaplan-Meier Estimate; Leucovorin; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Rectal Neoplasms; Retrospective Studies; Risk Assessment; Risk Factors; Tegafur; Time Factors; Treatment Outcome

A 61-year-old man had undergone five courses of modified FOLFOX6(mFOLFOX6)chemotherapy with calcium-magnesium(Ca/Mg)infusion for a rectal cancer with multiple liver metastases from October 2008. After this treatment, the primary rectal tumor and metastatic tumors were considered as a partial response(PR), and lower anterior resection was carried out in February 2009. After the operation, mFOLFOX6 chemotherapy with bevacizumab was started in March 2009. After 15 courses of chemotherapy, the patient received 7. 5 g of gosha-jinki-gan(TJ-107)daily from August 2009, and the drug compliance was 69%. From the 18th course of chemotherapy in October 2009, glutathione(GSH)was given at a dose of 200 mg before each oxaliplatin administration. From the 35th course of chemotherapy in November 2010, the patient received 1. 5 g of powdered processed aconite root(TJ-3027)daily. TJ-3027 administration was escalated to 4. 5 g daily, and drug compliance was 73%. Grade 4 neutropenia was observed in December 2010, and we reduced oxaliplatin to 65 mg/m(2) from the 37th course. Fifty chemotherapy courses were administered until October 2011. The patient received a total 3, 970 mg/m(2) of oxaliplatin, however, the neurotoxicity level of the patient remained at grade 2. Ca/Mg infusion and TJ-107 administration have been reported not to reduce the activity of FOLFOX individually, and severe side effects are rare. So one must consider the combination treatment of Ca/Mg and TJ-107 for prevention of oxaliplatin-related neurotoxicity.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Organoplatinum Compounds; Peripheral Nervous System Diseases; Rectal Neoplasms; Time Factors

To investigate serum carcinoembryonic antigen (CEA) as a prognostic factor for rectal cancer patients receiving pre-operative chemoradiotherapy (CRT).. Between 2000 and 2009, 138 patients with advanced rectal cancer receiving CRT before surgery at our hospital were retrospectively classified into 3 groups: pre-CRT CEA <6 ng/ml (group L; n = 87); pre-CRT CEA ≥ 6 ng/ml and post-CRT CEA <6 ng/ml (group H-L; n = 32); and both pre- and post-CRT CEA ≥ 6 ng/ml (group H-H; n = 19). CEA ratio (defined as post-CRT CEA divided by pre-CRT CEA), post-CRT CEA level and other factors were reviewed for prediction of pathologic complete response (pCR).. Five-year disease-free survival (DFS) was better in groups L (69.0%) and H-L (74.5%) than in group H-H (44.9%) (p = 0.024). Pathologic complete response was observed in 19.5%, 21.9% and 5.3% of groups L, H-L and H-H respectively (p = 0.281). Multivariate analysis showed that ypN stage and pCR were independent prognostic factors for DFS and that post-CRT CEA level was independently predictive of pCR. As a whole, post-CRT CEA <2.61 ng/ml predicted pCR (sensitivity 76.0%; specificity 58.4%). For those with pre-CRT CEA ≥6 ng/ml, post-CRT CEA and CEA ratio both predicted pCR (sensitivity 87.5%, specificity 76.7%).. In patients with pre-CRT serum CEA ≥6 ng/ml, those with "normalized" CEA levels after CRT may have similar DFS to those with "normal" (<6 ng/ml) pre-CRT values. Post-CRT CEA level is a predictor for pCR, especially in those with pre-CRT CEA ≥6 ng/ml.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carcinoembryonic Antigen; Chemoradiotherapy; Female; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Preoperative Care; Prognosis; Rectal Neoplasms; Remission Induction; Retrospective Studies; Survival Rate; Tegafur; Uracil

Studies aimed at predicting individual responsiveness to preoperative chemoradiation therapy (CRT) are urgently needed, especially considering the risks associated with poorly responsive patients.. A 3-step strategy for the determination of CRT sensitivity is proposed based on (1) the screening of a human genome-wide single-nucleotide polymorphism (SNP) array in correlation with histopathologic tumor regression grade (TRG); (2) clinical association analysis of 113 patients treated with preoperative CRT; and (3) a cell-based functional assay for biological validation.. Genome-wide screening identified 9 SNPs associated with preoperative CRT responses. Positive responses (TRG 1-3) were obtained more frequently in patients carrying the reference allele (C) of the SNP CORO2A rs1985859 than in those with the substitution allele (T) (P=.01). Downregulation of CORO2A was significantly associated with reduced early apoptosis by 27% (P=.048) and 39% (P=.023) in RKO and COLO320DM colorectal cancer cells, respectively, as determined by flow cytometry. Reduced radiosensitivity was confirmed by colony-forming assays in the 2 colorectal cancer cells (P=.034 and .015, respectively). The SNP FAM101A rs7955740 was not associated with radiosensitivity in the clinical association analysis. However, downregulation of FAM101A significantly reduced early apoptosis by 29% in RKO cells (P=.047), and it enhanced colony formation in RKO cells (P=.001) and COLO320DM cells (P=.002).. CRT-sensitive SNP markers were identified using a novel 3-step process. The candidate marker CORO2A rs1985859 and the putative marker FAM101A rs7955740 may be of value for the prediction of radiosensitivity to preoperative CRT, although further validation is needed in large cohorts.

Topics: Alleles; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Biomarkers, Tumor; Capecitabine; Cell Line, Tumor; Chemoradiotherapy; Deoxycytidine; Female; Fluorouracil; Genetic Markers; Genome-Wide Association Study; Genotyping Techniques; Humans; Leucovorin; Male; Microfilament Proteins; Middle Aged; Preoperative Care; Radiation Tolerance; Rectal Neoplasms

The impact of neoadjuvant chemoradiation on immediate results of treatment of resectable cancer recti, using large-fractionized radiation in combination with endolymphatic chemotherapy, was estimated. Using the method proposed 64 patients were treated (the main group). In control groups there were included 63 patients, to whom a course of a large-fractionized radiation on background of intravenous chemotherapy was applied, and in 91 patients a large-fractionized radiation only was used. The intraoperative complications rate in the main and control groups have had constituted, accordingly, 16, 6.3 and 3.3%. Postoperative complications have had occurred in 12.5% of patients in the main group, and in 15.9% and 14.3% - in the control groups. The abscesses formation was noted in a small pelvis cavity in 4.7% patients of the main, and in 4.8 and 4.4% - in the control groups. Necrosis of the descended gut was revealed in 10 (4.6%).

Topics: Adenocarcinoma; Antineoplastic Agents; Case-Control Studies; Disease-Free Survival; Female; Fluorouracil; Gamma Rays; Humans; Injections, Intralymphatic; Injections, Intravenous; Intraoperative Complications; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Grading; Postoperative Complications; Rectal Neoplasms; Vitamin B Complex

A 67-year-old woman presented with a history of dilated cardiomyopathy with congestive heart failure since 2003, who subsequently developed lower rectal cancer (adenocarcinoma) with liver, bone, and lymph node metastasis. Abdominoperineal resection and hepatectomy were performed. The patient received two rounds of intravenous chemotherapy, including 12 and six courses of FOLFOX4 (5-fluorouracil, leucovorin, and oxaliplatin; 85 mg/m(2) per cycle). She underwent a third round of intravenous FOLFOX4 because of tumor progression. During the 21(st) course of FOLFOX4 regimen, the patient developed ST segment depression in lead II and prolongation of QT interval with polymorphic ventricular tachycardia, torsades de pointes right after the start of oxaliplatin infusion. Immediate defibrillation and cardiopulmonary resuscitation were administered, and the patient regained spontaneous circulation and consciousness. Twelve-lead electrocardiogram showed ST segment elevation in III, aVF, and ST segment depression in V4-6 after resuscitation. To our knowledge, prolongation of QT interval with torsades de pointes and coronary spasm with myocardial injury that were stabilized in one patient following oxaliplatin infusion has not been reported. We present a patient with these rare complications.

Topics: Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cardiomyopathy, Dilated; Female; Fluorouracil; Humans; Leucovorin; Long QT Syndrome; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms; Torsades de Pointes

Management of locally advanced rectal cancer is complex because curative treatment routinely involves administration of surgery, chemotherapy, and radiation. Optimal treatment delivery sequencing and timing are challenging, and moreover, there is considerable heterogeneity in risk based on rectal tumor location, extent, and nodal involvement. The goal in rectal cancer treatment is to optimize disease-free and overall survival while minimizing the risk of local recurrence and toxicity from both radiation and systemic therapy. Currently, the standard approach to management of locally advanced (T3 or T2) rectal cancer involves careful staging with a pelvic MRI and proctoscopic evaluation by a surgeon experienced in total mesorectal excision. MRI can help to distinguish between patients in low-, intermediate-, and high-risk categories. Low-risk tumors have no evidence of either extramural spread or nodal involvement and proximal location in the rectum. For such patients, R0 resection is almost always possible and immediate surgery often is reasonable. In the minority of cases where unanticipated lymph node involvement is detected at surgical pathology, postoperative radiation can be administered. Patients who opt for up-front rectal surgery need to understand that although there is a chance that radiation can be avoided, if it is necessary, it is less well tolerated when administered postoperatively. Initial surgical treatment should be reserved for low-risk patients for whom imaging indicates and multidisciplinary team members feel is able to undergo an R0 resection with low chance for regional spread of disease. For patients with high-risk disease based on distal tumor location requiring an APR, threatened radial margins, or T4 tumors, preoperative chemoradiation is essential. Indeed, this approach increases the likelihood of complete surgical resection with negative margins. For some high-risk patients, for example those with T4 or bulky nodal disease, preoperative systemic therapy followed by preoperative chemoradiation and then surgery may be optimal. The feasibility of this approach is well established based on nonrandomized trials, but it has not been evaluated in a randomized study. Preoperative administration of systemic therapy can achieve clinical downstaging, optimize rates of sphincter preservation, and establish tumor responsiveness, which may be valuable for incorporation into future treatment decisions. For patients with intermediate-risk T3 r

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemoradiotherapy; Combined Modality Therapy; Deoxycytidine; Fluorouracil; Humans; Leucovorin; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Organoplatinum Compounds; Rectal Neoplasms

We report a case of advanced rectal cancer treated with chemotherapy, for which laparoscopic splenectomy had been effective for thrombocytopenia. A 56-year-old man suffered from advanced rectal cancer with multiple lung metastases. He underwent Hartmann's procedure and received chemotherapy with FOLFOX and FOLFIRI with bevacizumab. After 3 years and 2 months, he also suffered from splenomegaly and thrombocytopenia. Laparoscopic splenectomy produced and increased the thrombocyte count, allowing for a restart of chemotherapy. Oxaliplatin-based chemotherapy might produce hepatic sinusoid injury and induce splenomegaly owing to portal hypertension. Laparoscopic splenectomy seemed to be useful for treating thrombocytopenia, and allowed the continuation of chemotherapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Fatal Outcome; Fluorouracil; Humans; Laparoscopy; Leucovorin; Lung Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms; Splenectomy; Splenomegaly; Thrombocytopenia

A 58-year-old man underwent laparoscopic surgery for rectal cancer(rectal sigmoid)complicated by intestinal obstruction. He had no liver metastasis. Although many nodules suspected to have arisen from peritoneal dissemination were observed in the pelvic cavity, we performed anterior resection assuming that the primary lesion was resectable. The surgical findings were sSE, sN2, sP3, sStage IV, and histopathological findings were signet-ring cell carcinoma, pSE, pN2, pP+, pStage IV. After 8 courses of adjuvant chemotherapy with modified 5-fluorouracil/Leucovorin/oxaliplatin(mFOLFOX6), carcinoembryonic antigen( CEA)decreased to a normal level, and positron emission tomography-computed tomography(PET-CT)showed no abnormal accumulation that suggested metastasis. To evaluate the effectiveness of this procedure, laparoscopic peritoneal biopsy was performed 5 months after surgery, revealing histopathological disappearance of the peritoneal dissemination lesion. The patient has been followed up and has been receiving S-1 for 1 year after the first surgery. No evidence of recurrence has been observed.

Topics: Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Fluorouracil; Humans; Laparoscopy; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Peritoneal Neoplasms; Rectal Neoplasms; Tomography, X-Ray Computed

The use of preoperative chemoirradiation is the commonest treatment strategy employed in Malaysia for locally advanced rectal cancer. We need to determine the local control and survival rates for comparison with established rates in the literature.. This retrospective study analyzed all newly diagnosed patients with rectal adenocarcinoma who underwent long course preoperative radiotherapy (RT) at the Department of Radiotherapy and Oncology, Kuala Lumpur Hospital (HKL) between 1st January 2004 and 31st December 2010. The aim of the study was to determine the radiological response post radiotherapy, pathological response including circumferential resection margin (CRM) status, 3 years local control, 3 years overall survival (OS) and 3 years disease free survival (DFS). Statistical analysis was performed using the SPSS software. Kaplan-Meier and log rank analysis were used to determine survival outcomes.. A total of 507 patients with rectal cancer underwent RT at HKL. Sixty seven who underwent long course preoperative RT were eligible for this study. The median age at diagnosis was 60 years old with a range of 26-78 years. The median tumour location was 6 cm from the anal verge. Most patients had suspicion of mesorectum involvement (95.5%) while 28.4% of patients had enlarged pelvic nodes on staging CT scan. All patients underwent preoperative chemo-irradiation except for five who had preoperative RT alone. Only 38 patients underwent definitive surgery (56.7%). Five patients were deemed to be inoperable radiologically and 3 patients were found to have unresectable disease intraoperatively. The remaining 21 patients defaulted surgery (31.3%). The median time from completion of RT to surgery was 8 weeks (range 5.6 to 29.4 weeks). Fifteen patients (39.5%) had surgery more than 8 weeks after completion of RT. Complete pathological response was noted in 4 patients (10.5%). The pathological CRM positive rate after RT was 18.4%. With a median follow-up of 38.8 months, the 3 year local control rate was 67%. The 3 years rate for CRM positive (<2 mm), CRM clear (>2 mm) and pCR groups were 0%, 88.1% and 100% respectively (p-value of 0.007). The 3 year OS and DFS were 57.3% and 44.8% respectively.. In conclusion, the approach of long course preoperative chemoirradiation for rectal cancer needs to be re-examined in our local setting. The high rate of local recurrence is worrying and is mainly due to patient defaulting post-preoperative chemoirradiation or delayed definitive surgery.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Developing Countries; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Preoperative Care; Prognosis; Radiotherapy Dosage; Rectal Neoplasms; Retrospective Studies; Survival Rate

This study evaluated the safety and efficiency of preoperative chemoradiation therapy (CRT) with the XELOX or FOLFOX regimen in locally advanced rectal cancer patients.. One hundred forty-four patients (T3/T4 or N+) were enrolled between 2005 and 2011. The patients received preoperative concomitant CRT (XELOX or FOLFOX regimen). Patients were divided into four groups: pCR (pT0N0), downstaging, no-downstaging, and progression group. Clinical outcome with overall survival (OS) and disease-free survival (DFS) were compared for each group.. One hundred thirty-eight patients received radical resection after preoperative CRT. Twenty-seven patients (20%) achieved pCR. The response rate (pCR + downstaging) was 67%. The most common side effects were nausea (64%), diarrhea (49%), and leucopenia (49%). The overall estimated 5-year OS was 86% for all patients. The estimated 5-year OS was significantly better in the responders (pCR + downstaging) than the non-responders (no-downstaging + progression, 94% vs. 68%, P = 0.001). There was also statistical difference in 3-year DFS between the two groups (93% vs. 68%, P = 0.000).. pCR and downstaging after neoadjuvant CRT are associated with improved survival for locally advanced rectal cancer patients. Preoperative CRT with the XELOX or FOLFOX regimen is well tolerated and has mild adverse events.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemoradiotherapy; Deoxycytidine; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaloacetates; Rectal Neoplasms; Treatment Outcome

There is no consensus for laparoscopy first in patients with rectal cancer and synchronous liver metastases, whose metastases are confined to the liver. This study aimed to evaluate its indications for one-stage surgery in laparoscopy.. Eighteen patients with rectal cancer and synchronous liver metastases, who had undergone laparoscopic colorectal resection and simultaneous treatment for liver metastases, were retrospectively reviewed.. Concomitant with laparoscopic colorectal resection, eight patients received liver resection simultaneously; 10 patients underwent a variety of down-staging management including local ablation, right hepatic portal vein ligation, and implantation of chemotherapy pumps into the hepatic artery. The colo-anal/rectal anastomoses were performed with a stapler or "pull-though" mode though the anus. Three patients underwent two-stage liver resection following tumor down-staging. Median survival time was 22.3 months.. Laparoscopy approach for rectal cancer and synchronous liver metastases is feasible in selected patients. Colon pull-through anastomosis was a potential method to avoid abdominal incision and decrease the risk of anastomotic leakage. It is worth further investigation regarding its advantages over traditional modalities with a prospective randomized controlled study.

Topics: Adenocarcinoma; Adult; Aged; Anal Canal; Anastomosis, Surgical; Antineoplastic Combined Chemotherapy Protocols; Colon; Female; Fluorouracil; Hepatectomy; Hepatic Veins; Humans; Infusion Pumps, Implantable; Laparoscopy; Leucovorin; Ligation; Liver Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Rectal Neoplasms; Retrospective Studies; Time Factors; Young Adult

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemoradiotherapy; Cisplatin; Disease-Free Survival; Female; Fluorodeoxyglucose F18; Fluorouracil; Hepatectomy; Humans; Leucovorin; Liver Neoplasms; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Mitomycin; Multimodal Imaging; Neoadjuvant Therapy; Positron-Emission Tomography; Radiopharmaceuticals; Radiotherapy, Intensity-Modulated; Rectal Neoplasms; Tomography, X-Ray Computed

Accumulating evidence indicates that cancer-initiating cells (CICs) are responsible for cancer initiation, relapse, and metastasis. Colorectal carcinoma (CRC) is typically classified into proximal colon, distal colon, and rectal cancer. The gradual changes in CRC molecular features within the bowel may have considerable implications in colon and rectal CICs. Unfortunately, limited information is available on CICs derived from rectal cancer, although colon CICs have been described. Here we identified rectal CICs (R-CICs) that possess differentiation potential in tumors derived from patients with rectal adenocarcinoma. The R-CICs carried both CD44 and CD54 surface markers, while R-CICs and their immediate progenies carried potential epithelial-mesenchymal transition characteristics. These R-CICs generated tumors similar to their tumor of origin when injected into immunodeficient mice, differentiated into rectal epithelial cells in vitro, and were capable of self-renewal both in vitro and in vivo. More importantly, subpopulations of R-CICs resisted both 5-fluorouracil/calcium folinate/oxaliplatin (FolFox) and cetuximab treatment, which are the most common therapeutic regimens used for patients with advanced or metastatic rectal cancer. Thus, the identification, expansion, and properties of R-CICs provide an ideal cellular model to further investigate tumor progression and determine therapeutic resistance in these patients.

Topics: Adenocarcinoma; Animals; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Carcinogenesis; Cell Differentiation; Cell Proliferation; Cetuximab; Culture Media, Serum-Free; Drug Resistance, Neoplasm; Epithelial-Mesenchymal Transition; Fluorouracil; Humans; Hyaluronan Receptors; Intercellular Adhesion Molecule-1; Leucovorin; Mesoderm; Mice; Neoplastic Stem Cells; Organoplatinum Compounds; Phenotype; Rectal Neoplasms; Spheroids, Cellular; Xenograft Model Antitumor Assays

Hepatitis Bvirus (HBV)reactivation induced by cancer chemotherapy is increasingly being observed. However, most reports of resolved HBV[hepatitis Bsurface antigen(HBs-Ag)negative and hepatitis Bsurface antibody(HBs-Ab)positive and/or hepatitis Bcore antibody(HBc-Ab)positive]infection involve patients with hematological malignancies, whereas few describe patients with solid cancers. In this study, we report our experience with a patient with resolved HBV infection who was undergoing bevacizumab plus FOLFIRI treatment for rectal cancer when HBV reactivation was noted. This 74-year-old man was HBs-Ag negative, HBs-Ab negative, HBcAb positive, hepatitis B e antigen(HBe-Ag)negative, and hepatitis Be antibody(HBe-Ab)negative and had HBV-DNA levels below the detection limit. Forty-two days after the 21st cycle of bevacizumab plus FOLFIRI treatment, his aspartate aminotransferase and alanine aminotransferase levels increased. At followup examination, he was HBs-Ag positive, HBs-Ab negative, HBc-Ab positive, HBe-Ag positive, and HBe-Ab positive, while his HBV-DNA levels had increased to>9.0 log copies/mL, confirming HBV reactivation. His treatment included entecavir(0.5mg/ day)administration and plasmapheresis, but he succumbed to liver failure 82 days after his final dose of bevacizumab plus FOLFIRI. Thus, HBV reactivation can occur during bevacizumab plus FOLFIRI treatment in rectal cancer patients with a resolved prior HBV infection. No similar report has been published to date, and we believe that this study will be important when discussing HBV reactivation in patients with resolved HBV infection. Future studies will require detailed investigations in a larger number of institutions.

Topics: Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Fluorouracil; Hepatitis B; Hepatitis B virus; Humans; Leucovorin; Male; Rectal Neoplasms; Virus Activation

Colorectal cancer associated with Crohn's disease (CD) is increasing in proportion to the number of patients with CD in Japan. There are two subtypes of colorectal cancer with CD: sporadic cancer and colitis-associated cancer. Early diagnosis of colitis-associated cancer is sometimes difficult; when colorectal cancer is found in patients with CD, both colitis-associated cancer and sporadic cancer should be kept in mind. Here, we describe a case of metachronous, colitis-associated rectal cancer that developed after the complete resection of an adenoma that became a sporadic adenocarcinoma in a patient with longstanding CD. To the best of our knowledge, this is the first report of colitis-associated cancer in a patient with CD after removal of a sporadic cancer.. We describe a 51-year old man with CD who had difficulty in defecation. A rectal polyp was detected and a transanal resection of the polyp was performed. A histopathological examination showed an adenoma with sporadic adenocarcinoma. After three years, a follow-up colonoscopy revealed a reddish, elevated lesion in the patient's rectum. A colonoscopic biopsy showed a signet ring cell carcinoma. We performed an abdominoperineal resection of the rectum and a bilateral pelvic lymph node dissection. A histopathological examination revealed a mucinous adenocarcinoma with signet ring cell carcinoma and lymph node metastasis. The patient received adjuvant chemotherapy with oral uracil 224 mg combined with tegafur 100 mg plus leucovorin. No signs of recurrence were noted at a follow-up 18 months after the third surgery and 60 months after the second surgery.

Topics: Adenocarcinoma, Mucinous; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Signet Ring Cell; Combined Modality Therapy; Crohn Disease; Humans; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoplasms, Second Primary; Prognosis; Rectal Neoplasms; Tegafur; Uracil

To assess the efficacy and safety of bevacizumab (BEV) plus chemotherapeutic agents in the treatment of metastatic colorectal cancer (mCRC).. Seventy-seven mCRC patients received BEV plus 5-Fu type, oxaliplatin or irinotecan-based chemotherapy. The clinical efficacy and bevacizumab-related adverse reactions were observed. The efficacy assessment was conducted after at least 2 cycles of BEV therapy. The adverse reactions were recorded in each therapy cycle. Among the 77 cases, 64 patients had finished the efficacy assessment. The adverse reactions in all patients were assessed.. The overall response rate (ORR) of BEV plus chemotherapy regimen was 18.75% (12/64), and the disease control rate (DCR) was 75.0% (48/64). In 27 patients who received the regimen as first-line treatment, the ORR reached 37.0% (10/27), while the DCR was 85.2%. Four patients with potentially resectable lesions became resectable after the regimen and received R0 resection of the liver metastases successfully. Twenty-five patients who received the regimen as second line therapy had poor result with ORR 8.0% and DCR 76.0%. Hypertension was observed in 12 cases, with 8 cases of grade 1, 3 cases of grade 2, 1 case of grade 3. Various bleedings occurred in 24/77 cases (31.2%), all were of grade 1-2, including 17 cases of epistaxis, grade 1 hemorrhoid bleeding in one case, hematuria in 3 case (2 of grade 1, 1 of grade 2), GI bleeding in 2 cases, hemoptysis in 1 case (grade 2), and proteinuria in 4 cases (grade 1). Intestinal perforation occurred in 1 case (0.3%). In two patients who had incomplete intestinal obstruction history appeared exacerbated intestinal obstruction symptoms after the application of BEV plus CPT11 regimen.. BEV plus chemotherapy regimen as first-line treatment can improve the ORR and DCR of mCRC patients. When it was used as second- or later-line therapy, it may display satisfied DCR, although with a poor efficacy. The bevacizumab-related toxicity is mild and can be well tolerated.

Topics: Adult; Aged; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Capecitabine; Colonic Neoplasms; Deoxycytidine; Disease-Free Survival; Female; Fluorouracil; Follow-Up Studies; Hemorrhage; Humans; Hypertension; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaloacetates; Proteinuria; Rectal Neoplasms; Remission Induction; Young Adult

The purpose of this study was to investigate the value of postoperative chemotherapy for locally advanced rectal cancer patients who reached pathological ypT1-4N0 after neo-adjuvant chemoradiotherapy.. We performed a retrospective study of 104 patients treated with preoperative chemoradiotherapy followed by radical resection, who achieved pathological ypT1-4N0, between Mar 2003 and Dec 2010. There were 73 patients who received postoperative adjuvant chemotherapy, and the other 31 patients did not. The distribution of final pathologic stages for these patients was ypT1-2N0 in 39 cases and ypT3-4N0 in 65 cases.. The median follow-up was 41 months. The 3-year overall survival rate (OS) and recurrence-free survival rate (RFS) for the whole group (ypT1-4N0) were 93.4% and 85.3%, respectively. The 3-year OS and RFS in the adjuvant chemotherapy group and non-adjuvant chemotherapy group were 95.5%, 88.6% and 88.6%, 77.2%, respectively. There were no significant differences in 3-year RFS (P = 0.108) and OS (P = 0.106) between the two groups. The 3-year local recurrence and distant metastasis rates in the adjuvant chemotherapy group were 4.1% (3/73) and 5.5% (4/73), while for the non-adjuvant chemotherapy group, the 3-year local recurrence rate and distant metastasis rate were 3.2% (1/31) and 16.1% (5/31), respectively. Significant difference was found in distant metastasis rates (P = 0.030) between the two groups, but not in local recurrence rates (P = 0.676).Further subgroup analysis indicated that for the ypT1-2N0 patients, there were no significant differences in 3-year OS (P = 0.296) and RFS (P = 0.939) between the adjuvant and non-adjuvant chemotherapy groups, while negative results displayed in 3-year local recurrence rates (P = 0.676) and distant metastasis rates (P = 0.414). However, for patients with ypT3-4N0, significant differences were showed in both the 3-year OS (P = 0.034) and RFS (P = 0.025), and further analysis revealed that the 3-year distant metastasis rate was significantly higher in the non-adjuvant chemotherapy group than in the adjuvant chemotherapy group (P = 0.010) , but with non-significant difference in the 3-year local recurrence (P = 0.548).. Adjuvant chemotherapy may not improve survival for ypT1-2N0 patients. However, it may be clinically meaningful for ypT3-4N0 patients by decreasing distant metastasis rate. Further randomized controlled clinical trials are needed to confirm our results.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemoradiotherapy, Adjuvant; Chemotherapy, Adjuvant; Deoxycytidine; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasm Staging; Organoplatinum Compounds; Oxaloacetates; Postoperative Period; Radiotherapy, Conformal; Rectal Neoplasms; Retrospective Studies; Survival Rate; Young Adult

A 58-year-old woman had a very large advanced rectal cancer( with wild-type K-RAS expression). Abdominal computed tomography( CT) revealed a space-occupying lesion in the pelvis and an enlarged lymph node. We established a diagnosis of unresectable rectal cancer and subsequently performed transverse colostomy. The patient received 6 courses of Leucovorin, fluorouracil, and oxaliplatin( mFOLFOX6) plus panitumumab( Pmab), 2 courses of simplified Leucovorin plus 5-fluorouraci(l sLV5-FU) plus Pmab, and 1 course of Pmab. The size of the primary tumor decreased remarkably after chemotherapy. Low anterior resection was performed. The pathological stage was T4a, N0, M1, Stage IVa. The results from this case suggest that mFOLFOX6 plus Pmab preoperative chemotherapy is a useful regimen for the treatment of locally advanced K-RAS wild-type rectal cancer.

Topics: Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Panitumumab; Rectal Neoplasms

A 69-year-old man diagnosed with lower rectal cancer was referred to our hospital. Rectal examination and colonoscopy showed a type 2 circular tumor, 2.5 cm from the anal verge. Biopsy led to a diagnosis of moderately differentiated adenocarcinoma. Computed tomography (CT) and magnetic resonance imaging (MRI) showed signs of invasion to the surrounding organs and metastasis to the mesorectal fascia and left obturator lymph node (cAI, cN3). Therefore, we decided to start neoadjuvant chemotherapy with leucovorin calcium( folinic acid), fluorouracil, and oxaliplatin( mFOLFOX6). The patient received six courses of chemotherapy. CT and MRI after chemotherapy showed a reduction in tumor size. Six weeks after chemotherapy, the patient underwent intersphincteric resection with ileostomy. Pathological examination demonstrated no residual cancer cells in the primary lesion or lymph node (Grade III, pathological complete response [pCR]). This study demonstrates that neoadjuvant chemotherapy can be a promising option for locally advanced rectal cancer.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Leucovorin; Lymphatic Metastasis; Male; Neoadjuvant Therapy; Neoplasm Invasiveness; Organoplatinum Compounds; Rectal Neoplasms

In cases of advanced rectal cancer, preoperative chemoradiotherapy( CRT) serves to improve the local control rate, survival rate, radical resection rate, and/or probability of sphincter muscle preservation. According to the Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2010 for the treatment of colorectal cancer, preoperative CRT is the standard treatment for rectal cancer in Europe and the United States. However, there is insufficient evidence in support of its efficacy and safety in Japan, and therefore, CRT needs to be evaluated in properly designed clinical trials. Recently, several studies have reported on the efficacy of preoperative CRT in Japan. Herein, we report a case of rectal cancer in which radical resection was successfully performed with neo-adjuvant CRT.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Rectal Neoplasms; Recurrence; Treatment Outcome

A 51-year-old male patient visited our hospital with a complaint of anal dysfunction and anal pain. Colonoscopy revealed a lower rectal cancer just above the dentate line, and its biopsy showed endocrine cell carcinoma. Enhanced computed tomography( CT) showed pararectal and right inguinal lymph node metastasis. Leucovorin, 5-fluorouracil, and oxaliplatin (FOLFOX) therapy was initiated first; then, after K-RAS was found to be wild type, 6 courses of FOLFOX plus panitumumab were administered. After the chemotherapy, the main tumor and the lymph node swelling reduced evidently. Its effect was judged as a partial response (PR). Laparoscopic assisted intersphincteric resection, right inguinal lymph node dissection, and temporary ileostomy were performed. The pathology revealed endocrine cell carcinoma (MP, ly2, v2, n0, stage II). Its pathological effect was judged as Grade 1b. Five months after the surgery, the ileostomy was closed.

Topics: Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Endocrine Cells; Fluorouracil; Humans; Laparoscopy; Leucovorin; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Panitumumab; Rectal Neoplasms

Case1: A 63-year-old woman with diarrhea and hematochezia was diagnosed as having rectal cancer invading the pelvis. Six courses of the 5-fluorouracil, leucovorin, and oxaliplatin( mFOLFOX6) plus panitumumab regimen were administered after sigmoid colostomy, following which low anterior resection was performed. Since the 6 courses of mFOLFOX6 were administered postoperatively, no evidence of recurrence has been observed for 18 months. Case2: A 52-year-old man with high fever and abdominal pain was diagnosed as having rectal cancer invading the bladder with a vesicorectal fistula. After transverse colostomy and 6 courses of mFOLFOX6 plus panitumumab, high anterior resection with partial cystectomy was performed. Since the 8 courses of capecitabine plus oxaliplatin (XELOX) were administered postoperatively, no evidence of recurrence has been observed for 12 months. Although no consensus has been reached pertaining to the use of neoadjuvant chemotherapy for the treatment of colorectal cancer, we could, in this study, demonstrate the efficacy of neoadjuvant chemotherapy with panitumumab for the treatment of locally advanced colorectal cancer.

Topics: Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Invasiveness; Organoplatinum Compounds; Panitumumab; Rectal Neoplasms; Sigmoid Neoplasms

We encountered a case of colorectal cancer with pelvic abscess treated with radical surgery following colostomy and chemotherapy. The patient was a man in his 60s with advanced rectal cancer. The tumor had expanded locally and formed an abscess. We evaluated the primary lesion as unresectable, and performed chemotherapy with 5-fluorouracil, Leucovorin, and oxaliplatin( mFOLFOX) plus bevacizumab after colostomy. After 13 courses of chemotherapy, the tumor shrank remarkably. We performed a low anterior resection followed by adjuvant chemotherapy with capecitabine. The patient has had no recurrence for 18 months after surgery.

Topics: Abscess; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Combined Modality Therapy; Fluorouracil; Humans; Leucovorin; Male; Neoplasm Invasiveness; Organoplatinum Compounds; Rectal Neoplasms; Sigmoid Neoplasms

There is a lack of prognostic factors of preoperative chemoradiation for locally advanced rectal cancer. Thymidylate synthase (TS) is the most important target of 5-fluorouracil; three main genetic polymorphisms of TS have been described. We analysed the prognostic value of these in patients with locally advanced rectal cancer treated with fluoropyrimidine-based chemoradiation.. Ninety-nine patients treated between November 2001 and March 2009 were included. All were treated by radiotherapy (5040 cGy) and concomitant fluoropyrimidine-based chemotherapy. Three polymorphisms were analysed: (i) a double (2R) or triple (3R) repeat of a 28 base pair (bp) tandem sequence upstream of the ATG codon initiation site in the 5'-terminal regulatory region, (ii) a functional G > C single nucleotide polymorphism present in the second repeat of the 3R alleles and (iii) a 6 bp deletion at nucleotide 1494 in the 3'-untranslated region. DNA was extracted from paraffin-embedded core biopsies taken from the tumour and the genotype was analysed using polymerase chain reaction restriction fragment length polymorphism.. The 6 bp polymorphism was significantly associated with disease-free survival (+ 6 bp/+ 6 bp vs-6 bp/-6 bp, P = 0.032 logistic regression). No differences were found in disease-free survival according to the other polymorphisms studied. No relationship was observed between the different TS genotypes and pathological regression.. The study suggests that the TS 6 bp polymorphism may be a predictor of disease-free survival in patients with locally advanced rectal cancer treated with fluoropyrimidine-based chemoradiation.

Topics: 3' Untranslated Regions; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Base Sequence; Capecitabine; Chemoradiotherapy, Adjuvant; Chemotherapy, Adjuvant; Deoxycytidine; Disease-Free Survival; Female; Fluorouracil; Genotype; Humans; Leucovorin; Male; Neoadjuvant Therapy; Neoplasm, Residual; Organoplatinum Compounds; Polymorphism, Genetic; Rectal Neoplasms; Sequence Deletion; Thymidylate Synthase

Toxicity from neoadjuvant chemoradiation therapy (NT) increases morbidity and limits therapeutic efficacy in patients with rectal cancer. The objective of this study was to determine whether specific polymorphisms in genes associated with rectal cancer response to NT were correlated with NT-related toxicity.. One hundred thirty-two patients with locally advanced rectal cancer received NT followed by surgery. All patients received 5-fluorouracil (5-FU) and radiation (RT), and 80 patients also received modified infusional 5-FU, folinic acid, and oxaliplatin chemotherapy (mFOLFOX-6). Grade ≥3 adverse events (AEs) that occurred during 5-FU/RT and during combined 5-FU/RT + mFOLFOX-6 were recorded. Pretreatment biopsy specimens and normal rectal tissues were collected from all patients. DNA was extracted and screened for 22 polymorphisms in 17 genes that have been associated with response to NT. Polymorphisms were correlated with treatment-related grade ≥3 AEs.. Overall, 27 of 132 patients (20%) had grade ≥3 AEs; 18 patients had a complication associated only with 5-FU/RT, 3 patients experienced toxicity only during mFOLFOX-6, and 6 patients had grade ≥3 AEs associated with both treatments before surgery. Polymorphisms in the genes x-ray repair complementing defective repair in Chinese hamster cells 1 (XRCC1), xeroderma pigmentosum group D (XPD), and tumor protein 53 (TP53) were associated with grade ≥3 AEs during NT (P < .05). Specifically, 2 polymorphisms-an arginine-to-glutamine substitution at codon 399 (Q399R) in XRCC1 and a lysine-to-glutamine substitution at codon 751 (K751Q) in XPD-were associated with increased toxicity to 5-FU/RT (P < .05), and an arginine-to-proline substitution at codon 72 (R72P) in TP53 was associated with increased toxicity to mFOLFOX-6 (P = .008).. Specific polymorphisms in XRCC1, XPD, and TP53 were associated with increased toxicity to NT in patients with rectal cancer. The current results indicated that polymorphism screening may help tailor treatment for patients by selecting therapies with the lowest risk of toxicity, thus increasing patient compliance.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Child; Child, Preschool; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaliplatin; Polymorphism, Genetic; Radiotherapy, Adjuvant; Rectal Neoplasms; Young Adult

Surgical resection of asymptomatic primary colorectal cancer in patients presenting with synchronous unresectable metastatic disease is controversial. Concerns and controversies remain over combining cytotoxic chemotherapy with bevacizumab in this patient population.. We identified medical records of 99 patients with synchronous metastatic primary colorectal cancer who received chemotherapy with bevacizumab as their initial treatment. The incidence of subsequent use of surgery and surgical outcomes were recorded. Patients were also assessed for overall survival.. Patients who received bevacizumab-containing chemotherapy for synchronous metastatic primary colorectal cancer were divided into the non-surgery and surgery groups according to the resection status of their asymptomatic primary tumor. In the non-surgery group, two patients (4.4%) underwent additional surgery, while three patients (5.7%) required surgery for rectovesical fistula in the surgery group. The median overall survival was 17 months for the non-surgery group (95% CI: 10.6-23.3 months) and 23 months for the surgery group (95% CI: 21.3-24.6 months; P = 0.322).. This study utilizing chemotherapy with bevacizumab did not result in an increased rate of morbidity related to the unresected primary tumor. Survival is not compromised by leaving the primary colon tumor intact.

Topics: Adenocarcinoma; Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Capecitabine; Colonic Neoplasms; Combined Modality Therapy; Deoxycytidine; Female; Fluorouracil; Follow-Up Studies; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Neoplasm Staging; Neoplasms, Multiple Primary; Organoplatinum Compounds; Oxaliplatin; Prognosis; Rectal Neoplasms; Retrospective Studies; Survival Rate; Young Adult

In locally advanced rectal cancer (LARC) patients, major response to neoadjuvant radiotherapy (NR) has been associated with favorable long-term outcomes. Positive pathologic nodal status was recently proven to be associated with poor prognosis even after total regression of primary tumor (ypT0). The aim of this study was to evaluate the rate of lymph node (LN) involvement in patients with complete (ypT0) or major (TRG1: very few viable tumor cells) response.. Included were patients with complete or major response after radiotherapy followed by surgery and histological examination of the whole specimen.. From 1996 to 2010, 245 patients with LARC were treated by NR. We collected clinical data for 53 patients (21.6 %) with ypT0 (n = 26, 49 %) or TRG1 (n = 27, 51 %) response. Sphincter-preserving surgery was performed in 40 patients (75 %). Overall, nine patients (16.9 %) presented LN involvement: 2 (7.7 %) in the ypT0 group and 7 (25.9 %) in the TRG1 group (NS). Patients with ypT3 tumors had significantly more invaded LN than patients with ypT1-T2 tumors (6 of 13 [46 %] vs 1 of 14 [7 %], p = .032). After median follow-up of 30 months (range, 1-160 months), 5-year disease-free and overall survivals were 88.2 and 89.0 %, respectively.. There was a clear cutoff between patients with ypT0-T2 (3 of 40, 7.5 %) and ypT3 (6 of 13, 46 %) concerning the incidence of metastatic LN in patients achieving pathologic complete or major response after NR. In patients with good clinical response, local full-thickness resection of the residual tumor could be a first step, followed by standard rectal resection in cases of ypT3.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Disease-Free Survival; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms; Remission Induction

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Leucovorin; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaliplatin; Pregnancy; Pregnancy Complications, Neoplastic; Pregnancy Outcome; Rectal Neoplasms; Tomography, X-Ray Computed

The patient was a 73-year-old female. After curative resection for rectal cancer with uterus invasion, UFT/Leucovorin was administered orally for 16 months. Three years and six months after the initial surgery, en bloc cystourethrectomy was performed to control the bleeding caused by a local recurrence invading the bladder and ureter. Although postoperative FOL- FOX4/bevacizumab therapy was started, bevacizumab was discontinued after 4 courses of treatment because an ulcer was confirmed at the sigmoid colon with stoma. The ulcer was relieved by conservative medical treatment. In this case, we attempted to make a quick response because the site of the ulcer could be easily observed. During chemotherapy. Therefore, it is necessary to carefully observe the patient's conditions.

Topics: Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Female; Fluorouracil; Humans; Leucovorin; Organoplatinum Compounds; Rectal Neoplasms; Recurrence; Sigmoid Diseases; Ulcer

We now describe the first example of a patient who developed perirenal hematoma during the course of bevacizumab-containing chemotherapy. A 59-years-old woman with metastatic rectal cancer treated with bevacizumab, who developed low back pain after 11 cycles of chemotherapy. CT-scan was consistent with perirenal hematoma and discontinuation of bevacizumab resulted in symptomatic improvement. Nontraumatic perirenal hematoma is a rare condition that can cause shock in severe cases. Given that several types of bleeding complication are known to be associated with bevacizumab treatment, we concluded that bevacizumab likely contributed to the perirenal hematoma in this case. Although the appropriate modification of bevacizumab treatment in the setting of perirenal hematoma is still unclear, physicians should be aware of this potential bevacizumab-associated bleeding complication.

Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Female; Fluorouracil; Hematoma; Hemorrhage; Humans; Leucovorin; Liver Neoplasms; Middle Aged; Organoplatinum Compounds; Rectal Neoplasms; Time Factors; Tomography, X-Ray Computed

To evaluate whether postoperative low pelvic radiotherapy (RT) combined with chemotherapy is an appropriate treatment for stage II and III rectal cancer.. Between November 1997 and May 2006, 104 patients with stage II and III rectal cancer underwent surgery as the primary treatment followed by postoperative RT combined with chemotherapy in our institute and were reviewed retrospectively. Sixty-nine patients received low pelvic RT only (upper margin at 1 cm above the low end of the sacroiliac joint; median dose 54 Gy) (low pelvic RT group) and the other 35 patients received whole pelvic RT (upper margin at the mid L5; median dose 43.2 Gy) and subsequently received a boost to the low pelvis (total median dose 54 Gy) (whole pelvic RT group).. The 5-year overall survival rate, local control rate, and distant metastasis-free rate were 72% versus 63%, 86% versus 84%, and 66% versus 62% for low pelvic versus whole pelvic RT group. There were no statistical differences in these 2 groups. Two patients (2.9%) of the low pelvic RT group and 2 patients (5.7%) of the whole pelvic RT group developed upper pelvis relapse, which was out of the low pelvic field. The incidence of Grade 3 to 5 small bowel late complications of the low pelvic RT group was significantly less than that of the whole pelvic RT group (4.3% vs. 20%) (P=0.029).. Low pelvic RT significantly reduces small bowel late complications and does not compromise the overall survival rate, local control rate, and distant metastasis-free rate.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Multivariate Analysis; Neoplasm Staging; Odds Ratio; Pelvis; Postoperative Period; Proportional Hazards Models; Radiotherapy Dosage; Rectal Neoplasms; Retrospective Studies; Survival Analysis; Treatment Outcome

To investigate, in a comparative analysis, the prognostic implications of postchemoradiotherapy (post-CRT) pathologic stage (ypStage) vs. postoperative pathologic stage (pStage) in rectal cancer.. Between May 2001 and December 2006, 487 patients with T3 mid or distal rectal cancer were analyzed retrospectively. Concurrent CRT was administered preoperatively (n = 364, 74.7%) or postoperatively (n = 123, 25.3%). The radiation dose was 50.4 Gy in 28 fractions. All patients underwent a total mesorectal excision and received adjuvant chemotherapy. Disease-free survival (DFS) was estimated using the Kaplan-Meier method. Differences in DFS, stratified by ypStage and pStage, were compared using the log-rank test.. For surviving patients, the median follow-up period was 68 months (range, 12-105 months). The 5-year local recurrence-free survival rate was not different, at 95.3% and 92.1% in preoperative and postoperative CRT groups, respectively (p = 0.402), but the 5-year distant metastasis-free survival rate was significantly different, at 81.6% (preoperative CRT) vs. 65.4% (postoperative CRT; p = 0.001). The 5-year DFS rate of 78.8% in the preoperative CRT group was significantly better than the 63.0% rate in the postoperative CRT group (p = 0.002). Post-CRT pathologic Stage 0-I occurred in 42.6% (155 of 364) of the patients with preoperative CRT. The 5-year DFS rates were 90.2% (ypStage 0-I), 83.5% (ypStage II), 77.3% (pStage II), 58.6% (ypStage III), and 54.7% (pStage III). The DFS rate of ypStage 0-I was significantly better than that of ypStage II or pStage II. Post-CRT pathologic Stage II and III had similar DFS, compared with pStage II and III, respectively.. Disease-free survival predicted by each ypStage was similar to that predicted by the respective pStage. Improved DFS with preoperative vs. postoperative CRT was associated with the ypStage 0-I group that showed a similarly favorable outcome to pStage I rectal cancer.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Capecitabine; Chemoradiotherapy; Chemotherapy, Adjuvant; Deoxycytidine; Disease-Free Survival; Dose Fractionation, Radiation; Drug Administration Schedule; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Neoplasm Staging; Postoperative Period; Preoperative Period; Prognosis; Rectal Neoplasms; Retrospective Studies; Survival Rate; Time Factors

This study prospectively assessed the value of sequential fluorine-18-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) scans for predicting the response of locally advanced rectal cancer to neoadjuvant chemoradiation.. Fifty consecutive patients with locally advanced rectal cancer were enrolled. The treatment consisted of concurrent chemoradiation, which included preoperative 5-fluorouracil-based chemotherapy and pelvic radiation (4500 to 5040 cGy); this was followed 8 weeks later (median: 55 d) by surgery with a curative intent. All the patients underwent FDG-PET/CT before and 5 weeks later (median: 35 d) after the completion of chemoradiation. We evaluated the measurements of the FDG uptake [maximum standardized uptake values (SUV(max))] and the percentage of SUV(max) difference [(response index (RI)] between the prechemoradiation and postchemoradiation FDG-PET/CT scans.. After chemoradiation, 32 of 50 patients (64%) were classified as responders according to the tumor regression grade, which is based on the ratio of fibrosis to residual cancer (tumor regression grade 3-4). For all the patients, the mean prechemoradiation SUV(max) was 14.8, and this was significantly higher than the mean SUV(max) value of 6.1 at postchemoradiation (P< 0.001). The mean RI was significantly higher in the responders than that in the nonresponder patients (62.6% vs. 31.2%, P = 0.001). The following parameters were obtained using a RI cutoff of 53.0% for defining a response to therapy: 75.0% sensitivity, 73.2% specificity, 82.8% positive predictive value, and 61.9% negative predictive value.. The FDG-PET/CT parameters, and especially the RI, may be best for assessing the neoadjuvant chemoradiation response of locally advanced rectal cancer and these values can potentially assist physicians for planning the optimal treatment.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Female; Fluorodeoxyglucose F18; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Multimodal Imaging; Neoadjuvant Therapy; Neoplasm Staging; Positron-Emission Tomography; Preoperative Care; Prognosis; Prospective Studies; Radiopharmaceuticals; Rectal Neoplasms; ROC Curve; Tomography, X-Ray Computed

To investigate the prognostic significance of tumor volume reduction rate (TVRR) after preoperative chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC).. In total, 430 primary LARC (cT3-4) patients who were treated with preoperative CRT and curative radical surgery between May 2002 and March 2008 were analyzed retrospectively. Pre- and post-CRT tumor volumes were measured using three-dimensional region-of-interest MR volumetry. Tumor volume reduction rate was determined using the equation TVRR (%) = (pre-CRT tumor volume--post-CRT tumor volume) × 100/pre-CRT tumor volume. The median follow-up period was 64 months (range, 27-99 months) for survivors. Endpoints were disease-free survival (DFS) and overall survival (OS).. The median TVRR was 70.2% (mean, 64.7% ± 22.6%; range, 0-100%). Downstaging (ypT0-2N0M0) occurred in 183 patients (42.6%). The 5-year DFS and OS rates were 77.7% and 86.3%, respectively. In the analysis that included pre-CRT and post-CRT tumor volumes and TVRR as continuous variables, only TVRR was an independent prognostic factor. Tumor volume reduction rate was categorized according to a cutoff value of 45% and included with clinicopathologic factors in the multivariate analysis; ypN status, circumferential resection margin, and TVRR were significant prognostic factors for both DFS and OS.. Tumor volume reduction rate was a significant prognostic factor in LARC patients receiving preoperative CRT. Tumor volume reduction rate data may be useful for tailoring surgery and postoperative adjuvant therapy after preoperative CRT.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Capecitabine; Chemoradiotherapy; Deoxycytidine; Female; Fluorouracil; Follow-Up Studies; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Multivariate Analysis; Neoplasm Staging; Preoperative Care; Rectal Neoplasms; Retrospective Studies; Tumor Burden

Pathological staging and regression grading may affect the clinical outcome in rectal carcinoma patients treated with neoadjuvant chemoradiation (NACRT). Oncocytic change (OC) has also been described in the residual tumor. This study assesses the correlation of degree of pathological response and OC with clinical outcome.. Seventy-five cases of rectal adenocarcinoma undergoing NACRT followed by surgery were retrospectively analyzed for preoperative and post-operative staging, degree of tumor response to NACRT using the Dworak Regression score (DR) and Tumor Regression Grading (TRG) systems, as well as the proportion of cells showing OC. These parameters were correlated with overall survival (OS) and disease-free survival (DFS).. Significant correlation was found between post-operative T and N stage and OS (P = 0.005 and 0.002, respectively); and post-operative and preoperative T stage with DFS (P = 0.002 and 0.02, respectively). Grouping patients by TRG scores (TRG1-3 vs TRG4-5) also proved to be a significant independent prognosticator for DFS (P < 0.001). The DR score groups and OC (<35% vs. >35%) were not statistically significant predictors of clinical outcome.. Post-NACRT T and N staging and the TRG system are important prognostic indicators. The presence and extent of OC needs to be better understood and further investigated.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Mitomycin; Neoadjuvant Therapy; Neoplasm Grading; Neoplasm Staging; Neoplasm, Residual; Postoperative Care; Rectal Neoplasms; Retrospective Studies; Survival Rate; Treatment Outcome

The 2010 NCCN clinical practice guidelines recommend radiation as a part of the standard adjuvant or neoadjuvant treatment for stage IV rectal cancer patients. This study evaluated the oncologic efficacy of postoperative radiotherapy (RTx) in loco-regional control after complete removal of primary and metastatic lesions in stage IV rectal cancer.. Sixty-eight patients with metastatic rectal cancer were enrolled and analyzed. Twenty-eight of the enrolled patients received concurrent postoperative RTx with chemotherapy (RTx group) and the remaining 40 received only postoperative systemic chemotherapy (CTx) without RTx (non-RTx group). The eligibility criteria were as follows: a primary rectal tumor located in the low or mid-rectum, no postoperative macroscopic and microscopic evidence of residual tumor in primary and metastatic sites, and no history of prior CTx or pelvic RTx.. The recurrence rates were 75.0% in the RTx group and 72.5% in the non-RTx group. Local recurrence rates were 7.1% (RTx group) and 22.5% (non-RTx group) (P = 0.108). There were no differences in overall survival (OS), local recurrence-free survival, and disease-free survival between the two groups. The 2-year OS rates were 78.9% (RTx group) and 74.1% (non-RTx group) (P = 0.395).. Survival benefit of postoperative RTx in stage IV rectal cancer after complete removal of tumors was not apparent. RTx could be recommended for selected patients at high risk of local recurrence or for palliation of symptoms.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Organoplatinum Compounds; Oxaliplatin; Postoperative Care; Radiotherapy, Adjuvant; Rectal Neoplasms; Retrospective Studies

A 60-year-old man underwent sigmoid loop colostomy for obstructive rectal cancer. Computed tomography (CT) showed a circumferential thickening of the lower rectal wall caused by a tumor invading the posterior and side pelvic wall. As we considered R0 resection too difficult, we gave the patient bevacizumab plus FOLFOX4 (oxaliplatin, leucovorin, and 5-fluorouracil). After eight courses, CT showed improvement in the rectal wall thickening but linear thickening of the mesorectal fascia remained. We therefore gave the patient chemoradiotherapy (CRT), and then 10 weeks later performed Hartmann's operation laparoscopically. Microscopic examination revealed that the tumor had been almost replaced by fibrous tissue, with only a few cancer cells left in the subserosa. The circumferential resection margin was free of cancer cells. The patient is doing well after 27 months of follow-up. This case suggests that systemic chemotherapy with FOLFOX4 plus bevacizumab prior to conventional preoperative CRT is a promising strategy for patients with initially unresectable locally advanced rectal cancer.

Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Chemoradiotherapy; Combined Modality Therapy; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Invasiveness; Organoplatinum Compounds; Pelvis; Rectal Neoplasms; Tomography, X-Ray Computed

The risks of chemoradiotherapy in elderly patients with rectal cancer have not yet been well-characterised.. We retrospectively reviewed the charts of patients with rectal cancer over 70 years old who were treated with chemoradiotherapy in two French university hospitals.. A total of 125 patients were evaluated. Mean age was 75.1 ± 4.1 years and ranged from 70 to 90 years. Adverse effects ≥ grade 2 were observed in 32% of the patients and adverse effects ≥ grade 3 in 15%. Dose reduction for toxicity was performed in 18% of the patients and chemoradiotherapy discontinuation was necessary in 9%. Postoperative morbidity was 16% with two treatment-related deaths. Two-year survival rate was 84%. No variables had any influence on treatment-related adverse events.. In selected elderly patients, chemoradiotherapy is well-tolerated, without any significant increase in adverse events, and the results are similar to those recorded in younger patients.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Capecitabine; Chemoradiotherapy, Adjuvant; Deoxycytidine; Disease-Free Survival; Female; Fluorouracil; France; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Neoplasm Metastasis; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms; Retrospective Studies; Tegafur; Vitamin B Complex

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Fluorouracil; Humans; Leucovorin; Male; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Rectal Neoplasms; Treatment Outcome

To investigate the outcomes of adjuvant chemotherapy (CT) or chemoradiotherapy (CRT) after simultaneous surgical resection in rectal cancer patients with liver metastases (LM).. One hundred and eight patients receiving total mesorectal excision for rectal cancer and surgical resection for LM were reviewed. Forty-eight patients received adjuvant CRT, and 60 were administered CT alone. Recurrence patterns and prognosis were analyzed. Disease-free survival (DFS) and overall survival (OS) rates were compared between the CRT and CT groups. The inverse probability of the treatment-weighted (IPTW) method based on the propensity score was used to adjust for selection bias between the two groups.. At a median follow-up period of 47.7 months, 77 (71.3%) patients had developed recurrences. The majority of recurrences (68.8%) occurred in distant organs. By contrast, the local recurrence rate was only 4.7%. Median DFS and OS were not significantly different between the CRT and CT groups. After applying the IPTW method, we observed no significant differences in terms of DFS (hazard ratio [HR], 1.347; 95% confidence interval [CI], 0.759-2.392; p = 0.309) and OS (HR, 1.413; CI, 0.752-2.653; p = 0.282). Multivariate analyses showed that unilobar distribution of LM and normal preoperative carcinoembryonic antigen level (<6 mg/mL) were significantly associated with longer DFS and OS.. The local recurrence rate after simultaneous resection of rectal cancer with LM was relatively low. DFS and OS rates were not different between the adjuvant CRT and CT groups. Adjuvant CRT may have a limited role in this setting. Further prospective randomized studies are required to evaluate optimal adjuvant treatment in these patients.

Topics: Adult; Aged; Analysis of Variance; Capecitabine; Chemoradiotherapy; Chemotherapy, Adjuvant; Deoxycytidine; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Organoplatinum Compounds; Oxaliplatin; Pelvis; Postoperative Care; Probability; Prognosis; Rectal Neoplasms; Retrospective Studies; Selection Bias

To evaluate the prognostic significance of the first postsurgery carcinoembryonic antigen (CEA) level in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation (nCRT) and total mesorectal excision.. A total of 100 patients underwent nCRT and had baseline and posttreatment CEA levels recorded within 6 months of surgery. The median radiotherapy dose was 50.4 Gy. Eighty-six patients received adjuvant 5-fluorouracil-based chemotherapy. Prognostic factors were analyzed for possible associations with freedom from failure (FFF) by univariate and multivariate analyses. Median follow-up was 30 months.. The median CEA (ng/ml) levels at baseline before nCRT, after nCRT, and after total mesorectal excision were 3.6, 1.7, and 1.3, respectively. Pathologic complete response was observed in 22%. FFF at 36 months was 78%. Local failure and distant failure occurred in 4 and 20% of the patients, respectively. On univariate analysis, pathologic complete response, margin status, and both pretreatment and postsurgery CEA levels were associated with recurrence (all P < 0.05). On multivariate analysis, pathologic complete response (P < 0.007), margin status (P < 0.001), and postsurgery CEA level (P = 0.003), but not baseline CEA level (P = 0.2), were found to be associated with recurrence.. After nCRT for rectal cancer, postsurgery CEA level may have more prognostic value than pretreatment level. Patients with a postsurgery CEA level of >2.5 ng/ml have higher rates of recurrence and may warrant closer surveillance.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carcinoembryonic Antigen; Chemotherapy, Adjuvant; Combined Modality Therapy; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Radiotherapy Dosage; Radiotherapy, Adjuvant; Rectal Neoplasms; Survival Rate; Young Adult

We report a patient with a huge multiple hepatic metastases of rectal cancer treated by combination of infusional 5-FU, Leucovorin, irinotecan(FOLFIRI), and bevacizumab(BV). The patient was a 60-year-old man with cancer of the rectum, with huge multiple hepatic metastases. The serum carcinoembryonic antigen(CEA)level was 3,979.6 ng/mL, and the carbohy- drate antigen(CA)19-9 level was 66,562.6 U/mL. The patient received combined chemotherapy with FOLFIRI and BV. After completion of 8 courses, abdominal CT scans revealed that those low-density areas of the liver had reduced. The patient was judged to have achieved PR. He received combined therapy for 42 courses, and his response is SD at this point. No grade 2 adverse event occurred throughout chemotherapy. This case suggests that combined therapy with FOLFIRI+BV may be an effective regimen for advanced rectal cancer with huge multiple hepatic metastases.

Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Biopsy; Camptothecin; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Quality of Life; Rectal Neoplasms; Tomography, X-Ray Computed

The response of rectal adenocarcinoma to neoadjuvant therapy is variable. Accurate prediction of response would enable selective administration of therapy. The enzyme glutathione S-transferase Pi (GSTP1) has been shown to influence response to therapy in some solid tumours. Few data are available for rectal cancer.. The GSTP1 levels in rectal adenocarcinoma and adjacent normal mucosa were quantified before and after exposure to neoadjuvant therapy. Venous blood samples and biopsies of normal rectal mucosa and tumour were prospectively obtained from patients with primary rectal cancer. Patients were stratified by exposure to neoadjuvant therapy or surgery alone. GSTP1 was quantitatively measured using an enzyme-linked immunosorbent assay.. Ninety-two patients (54 men; median age 68 years) were recruited. The median GSTP1 level was significantly higher in rectal adenocarcinoma than in matched normal mucosa [6.59 μg/mg vs 4.57 μg/mg; P < 0.001]. The median tumour GSTP1 level was significantly lower in the therapy group compared with unmatched samples from the no-therapy group [4.47 μg/mg vs 7.76 μg/mg; P < 0.001].. The GSTP1 level is increased in rectal adenocarcinoma compared with adjacent normal mucosa. It decreases following neoadjuvant therapy. Future studies correlating pre-therapy GSTP1 levels with pathological response would be of interest.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Female; Fluorouracil; Glutathione S-Transferase pi; Humans; Intestinal Mucosa; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Radiotherapy, Adjuvant; Rectal Neoplasms; Rectum; Statistics, Nonparametric

A 55-year-old male had complained of melena.Colonoscopy revealed a type 2 tumor at the rectum.CT demonstrated hepatic lymph nodes and multiple liver metastases(stage IV).Low anterior resection was performed(tub2, RsRa, circ, type 2, pSS, pN1, sH3, cHN1, sP0, cM0: fstage IV).The patient was treated with mFOLFOX6 and sLV5FU2 after operation.CT revealed a partial response after 14 courses of systemic chemotherapy.sLV5 FU2 therapy was converted to capecitabine because he experienced bone marrow suppression.CT showed that the liver metastases had enlarged but the hepatic lymph nodes disappeared.Right portal vein embolization was performed.After 4 weeks, right hepatectomy and hepatic lymph node dissection were performed.Preoperative chemotherapy with mFOLFOX6 seems beneficial as a neoadjuvant chemotherapy for hepatic lymph node-positive advanced colorectal cancer.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Rectal Neoplasms; Tomography, X-Ray Computed

To compare the short-term perioperative results and long-term oncologic outcomes between patients who underwent neoadjuvant chemoradiotherapy (NCRT) and patients who underwent postoperative adjuvant chemoradiotherapy (ACRT) for stage III rectal cancer.. From January 1997 to December 2008, a total of 47 patients who were diagnosed as clinical stage III rectal cancer followed by NCRT were matched according to age, gender, and operation method to 47 patients with pathologic stage III rectal cancer who underwent ACRT. Clinical characteristics, surgical and pathologic outcomes, postoperative complications and recovery, and oncologic outcomes were compared between the two groups.. There were no significant differences in demographics or preoperative characteristics between the NCRT and ACRT groups. Though more protective ileostomies were performed in the NCRT group, there was no statistical difference in operation times between the two groups. Patients in the NCRT group had a smaller tumor size (P < 0.001) and a smaller number of lymph nodes retrieved (P < 0.001). No differences were observed with respect to morbidity and recovery outcomes between the two groups. During the median 58-month follow-up periods, the NCRT group showed better disease-free survival and overall survival than the ACRT group (P = 0.002, P = 0.001, respectively).. NCRT in comparison to ACRT did not increase the risk of postoperative morbidity and provided better disease-free and overall survival in stage III rectal cancer patients.

Topics: Antineoplastic Combined Chemotherapy Protocols; Case-Control Studies; Chemoradiotherapy; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Grading; Neoplasm Recurrence, Local; Neoplasm Staging; Postoperative Period; Prognosis; Rectal Neoplasms; Survival Rate; Time Factors

To investigate the relationship between serum concentration of fluorouracil and therapeutic efficacy as well as adverse reactions in patients with unresectable locally advanced or measurable metastatic colorectal cancer, and to analyze its role in further improving therapeutic efficacy and reducing adverse reactions of fluorouracil-based chemotherapy.. Eighty-six patients were randomly assigned into three groups according to the average plasma concentration of fluorouracil after three cycles of chemotherapy with the initial regimen of two weeks FOLFOX-4 (oxaliplatin + leucovorin + fluorouracil) or FOLFIRI (irinotecan + leucovorin + fluorouracil): group 1 (plasma concentration of fluorouracil < 25 ng/ml), group 2 (25 - 35 ng/ml) and group 3 (> 35 ng/ml). The blood samples were taken at 12 h after continuous infusion of fluorouracil in each cycle and the plasma concentration of fluorouracil was detected by high performance liquid chromatography (HPLC) (about 5 am ± 1 h). The relationship between the drug plasma concentration, therapeutic efficacy and adverse reactions in different fluorouracil plasma concentration arms was analyzed retrospectively.. The average plasma concentrations of fluorouracil of the three groups were (23.48 ± 1.95) ng/ml, (31.47 ± 2.33) ng/ml and (39.89 ± 3.87) ng/ml, respectively (P < 0.01). As for therapeutic efficacy, the median OS of the groups 2 and 3 were 18.0 and 17.5 months, significantly higher than that in the group 1 (13.0 months, P < 0.01). The PFS were 4.5, 7.5 and 8.0 months, respectively (P < 0.01). In terms of adverse reactions, the incidences of bone marrow suppression, mucositis and diarrhea in the group 3 were significantly higher than that in the first two groups (P = 0.02, P = 0.04 and P = 0.02).. The patients with local advanced and metastatic colorectal cancer, receiving fluorouracil-based chemotherapy, and with an average plasma concentration of fluorouracil between 25 - 35 mg/L have a better prognosis, and lower incidence of adverse reactions such as bone marrow suppression, mucositis and diarrhea.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Diseases; Colonic Neoplasms; Diarrhea; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Mucositis; Neoplasm Staging; Organoplatinum Compounds; Random Allocation; Rectal Neoplasms; Remission Induction; Survival Rate

The patient was a 78-year-old woman with a chief complaint of abdominal bloating and constipation who was referred to us and was examined for an AV 12-15 cm, circumferential type 2 rectal cancer. The pathological diagnosis was adenocarcinoma (tub1+tub2). T4 and N2 were suspected based on the CT findings, and because the CEA value was high, the patient was treated with 7 courses of mFOLFOX6 neoadjuvant chemotherapy followed by salvage surgery(low anterior resection+D3). Examination of the surgical specimen revealed chronic inflammatory cell infiltration, including histiocytes accompanied by ulceration, and fibrosis was observed down to SS. No viable cancer cells were detected, and the tumor response was evaluated as a pathological CR. mFOLFOX6 appeared to be effective as neoadjuvant chemotherapy for advanced rectal cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Leucovorin; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Rectal Neoplasms

A 64-year-old man who underwent rectal amputation for rectal cancer was diagnosed with multiple liver metastases and tumor embolus in the portal vein 6 months after operation. Though the patient underwent chemotherapy, mFOLFOX6, and bevacizumab+FOLFIRI, liver metastases were diagnosed as progressive disease (PD). After panitumumab+FOLFIRI was administered for three months as third-line chemotherapy, the tumor embolus completely disappeared, and liver metastases became cytoreductive on CT. The patient was judged to have achieved a partial response (PR). This case indicated that panitumumab was effective as third-line chemotherapy for unresectable recurrent rectal cancer.

Topics: Antibodies, Monoclonal; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Embolism; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Organoplatinum Compounds; Panitumumab; Portal Vein; Rectal Neoplasms; Salvage Therapy

We report a case of complete remission after treatment with tegafur-uracil (UFT)/Leucovorin (LV) therapy for pulumonary metastasis of rectal cancer. A 56-year-old male was admitted to our hospital with a diagnosis of rectal cancer (Ra, type2). Chest CT on admission demonstrated bilateral lung metastases (rt S2 and lt S4). After anterior resection of the primary tumor, oral UFT/LV was administered (UFT 400 mg/LV 75 mg, 4-week administration and 1-week no-administration period) on an outpatient basis. After 2 courses, chest CT revealed reduction of both metastases, and complete resection of the metastases by video assisted thoracic surgery (VATS) was planned. Pathological findings of a specimen revealed no residual cancer cells, indicating a complete response to UFT/LV therapy. After these treatments, combined therapy of UFT/LV was continued for 3 months, and the single administration of UFT was continued for 1 year. The patient experienced no adverse reactions, and has had no recurrent disease in 4 years. Oral UFT/LV therapy is considered to be a promising regimen for patients with resectable metastatic lesion from a standpoint of clinical efficacy and safety.

Topics: Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Rectal Neoplasms; Remission Induction; Tegafur; Tomography, X-Ray Computed; Uracil

We evaluated the efficacy and safety of neoadjuvant chemotherapy using modified OPTIMOX1 plus bevacizumab for advanced rectal cancer.. Nine cases with highly advanced rectal cancer for which curative surgery was potentially difficult were enrolled(clinical T4 in 7 cases, lateral node metastasis in 3 cases, M1 in 2 cases).. The number of courses of modified OPTIMOX1(mFOLFOX6 and sLV5FU2, alternating administration)plus bevacizumab ranged from 1 to 21(median: 10). Surgical procedures consisted of internal sphincter resection(ISR)in 4 patients, ultra-low anterior resection(ULAR)in 2 patients, pelvic exenteration(TPE)in 2 patients, and Hartmann's procedure in 1 patient. Liver resection was conducted in 2 patients. RM1 was confirmed in 2 patients, but curative surgery was performed in the other patients. Histological efficacy of grade x/1a/1b/2were seen in the above 1/4/2/2 cases, respectively. Neurotoxicity associated with oxaliplatin was mild; no grade 3 neurotoxicity was noted. Recurrence has been confirmed in 5 patients at the median follow-up period of 650 days.. It was suggested that modified OPTIMOX1 plus bevacizumab is effective and safe to administer as a neoadjuvant chemotherapy for curative resection or anus-preserving surgery in patients with highly advanced rectal cancer.

Topics: Adult; Aged; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Prognosis; Rectal Neoplasms; Recurrence

To investigate the impact of concurrent chemoradiotherapy (CCRT) on stage IV rectum cancer.. Between 2000 and 2011, 297 consecutive patients diagnosed with stage IV rectum cancer (synchronous metastasis) were enrolled. Cox proportional hazard analyses were used for prognostic factors determination, and the Kaplan-Meier method was used for survival analyses. Propensity scores with the one-to-one nearest-neighbor matching model were used to select matched patients for validation studies.. In total, 63 patients received CCRT and 234 did not. The patients in the CCRT group were younger, had more low-lying lesions, and had more T4 lesions, lung metastases, metastasectomies, and oxaliplatin-based upfront chemotherapy. Before propensity-score matching, a younger age (HR = 0.662, P = 0.016), lower carcinoembryonic antigen (CEA) level (≤20 ng/ml) (HR = 0.531, P = 0.001), no metastasectomy (HR = 3.214, P < 0.001), and no CCRT (HR = 1.844, P = 0.019) were independent prognostic factors after controlling for other confounding factors. After matching, only CEA and metastasectomy, but not CCRT, were independent prognostic factors. The survival benefit of CCRT was restricted to patients who undergo subsequent metastasectomy.. Upfront CCRT only provided a survival benefit in patients with stage IV rectum cancer who undergo subsequent metastasectomy.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemoradiotherapy, Adjuvant; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Organoplatinum Compounds; Propensity Score; Rectal Neoplasms; Rectum; Retrospective Studies; Survival Analysis; Treatment Outcome

Although current guidelines recommend distal resection margins (DRM) of 2-5 cm in rectal cancer operation, smaller margins may be safe. We therefore assessed the impact of distal margins on outcomes in patients with rectal cancer treated with neoadjuvant chemoradiotherapy (CRT) followed by radical resection or resection followed by adjuvant CRT.. This study involved 376 patients who underwent sphincter-saving resection for rectal adenocarcinoma and pre- or postoperative CRT between 2000 and 2006. DRMs were measured on pinned fixed specimens. We excluded patients who did not complete planned CRT and those with stage IV disease. A retrospective cross-sectional analysis was performed.. No significant differences in local recurrence (9.8 versus 7.3%; P = 0.324) and systemic recurrence (16.4 versus 18.7%; P = 0.731) were observed in patients with DRMs of ≤5 and >5 mm, respectively. Moreover, in each DRM category, there were no differences in local and systemic recurrence rates between patients who received pre- or postoperative CRT. DRM did not affect overall survival (P = 0.880) or 5-year survival rate (80.3 versus76.8%; P = 0.340).. A distal margin of at least 5 mm with negative resection margin on frozen section does not reduce oncological safety in rectal cancer patients who receive pre- or postoperative CRT.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemoradiotherapy, Adjuvant; Cross-Sectional Studies; Deoxycytidine; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasm Staging; Rectal Neoplasms; Rectum; Retrospective Studies; Survival Analysis; Treatment Outcome

Controversy continues regarding the treatment of patients with resectable rectal cancer, particularly in regard to the effects of adjuvant therapies on long-term survival. The benefits of adjuvant chemotherapy alone in patients with stage III rectal cancer after curative resection remain unclear. The aim of this study was to compare the overall survival of patients who had received adjuvant chemotherapy after resection of a stage III rectal cancer (111 patients) with the survival of a historical control group who had surgery alone before chemotherapy was introduced (129 patients).. Treatment and outcomes data were drawn from a prospective hospital registry of consecutive patients who had a resection for stage III rectal cancer.. The estimated Kaplan-Meier overall 5-year survival rate in patients who received chemotherapy (68.7%, 95% CI 58.3-77.1%, log-rank P < 0.001) was improved compared with the historical controls (40.5%, 95% CI 31.4-49.5%, log-rank P < 0.001). No systematic differences between the treated and control group were found.. This study has shown improved survival after adjuvant chemotherapy in patients with stage III rectal cancer as compared with historical controls treated by surgery alone. Hence, there could be subsets of patients whom when treated with surgery in a specialized surgical unit, may benefit from chemotherapy and spared the toxicities of adjuvant radiotherapy. This should be explored further in a cooperative trial group setting.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cohort Studies; Female; Fluorouracil; Hospitals, Teaching; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Prospective Studies; Randomized Controlled Trials as Topic; Rectal Neoplasms; Registries; Treatment Outcome

The patient, a 75-year-old woman, who was referred to our hospital in April 2010 because of diarrhea and lower abdominal pain. Abdominal CT scan revealed a large tumor, over 8 cm in diameter within the pelvis, and colonoscopy detected rectal cancer. There was no obvious distant metastasis, although invasion to the uterus and regional lymph node metastasis was suspected. After admission, she had been suffering from tumor-accompanying symptoms such as fever, melena, and abdominal pain. Although loop sigmoid colostomy was performed, symptoms were unimproved, and the tumor had grown to 11 cm in diameter. Therefore, chemotherapy(mFOLFOX6)was started. After two courses of chemotherapy, the tumor-accompanying symptoms improved. Six courses of chemotherapy were administered, and subsequent examination revealed shrinkage of the tumor(effect judgment PR). Thirteen days after final chemotherapy, the tumor was successfully resected. Pathological diagnosis of the surgical specimen was tub2, pSI(sigmoid colon), pN0, and Stage II. The surgical margin was completely free of cancer(R0), and the histological effect of chemotherapy was judged as Grade 1b. The patient had received adjuvant chemotherapy with UFT+LV for half a year after discharge. She has been free from any sign of recurrence for 11 months. This case suggests that appropriate preoperative chemotherapy is useful for locally advanced rectal cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Magnetic Resonance Imaging; Neoplasm Invasiveness; Neoplasm Staging; Organoplatinum Compounds; Rectal Neoplasms

A 78-year-old man had undergone abdominoperineal resection for rectal cancer in 2003. After 7 years, he visited our hospital with complaints of turbid discharge from the stoma. A tumor 11 cm in diameter was shown at the site of the stoma. A partial resected biopsy revealed moderately-differentiated adenocarcinoma. We diagnosed metachronous multiple carcinoma or recurrent cancer at the colostomy site. After loop colostomy of the ascending colon was performed, systemic chemotherapy with mFOLFOX6 was performed. After 5 courses, the tumor revealed a significant reduction in its size. Afterwards, the stoma including the tumor and remaining left-side colon with adjacent abdominal wall was resected, keeping the surgical margin free. In the resected specimen, histological evaluation of the treatment with chemotherapy was assessed to be Grade 1a. As a result of preoperative chemotherapy, we finally were able to resect the minimal area of the adjacent skin and abdominal wall, and succeed in primary closure of the surgical wound. This case suggests that preoperative chemotherapy is a good option for treating cancer occurring at a colostomy site.

Topics: Abdominal Wall; Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Colostomy; Combined Modality Therapy; Fluorouracil; Humans; Leucovorin; Male; Neoplasm Grading; Organoplatinum Compounds; Rectal Neoplasms; Tomography, X-Ray Computed

A 48-year-old man, who had presented with anal pain and cloudy urine, was referred to our hospital. Colonoscopy showed a type 2 circular tumor at the higher rectum, and a diagnosis of well-differentiated adenocarcinoma was made by biopsy. CT demonstrated increased thickness of the rectum wall, an equivocal boundary between the rectum and the bladder, and abnormal gas production in the bladder. Following diagnosis of T4 rectal cancer, preoperative chemotherapy was initiated with the aim of downstaging the tumor and avoiding total pelvic exenteration. After 5 courses of mFOLFOX+bevacizumab, the tumor showed a partial response on CT, which enabled the tumor to be resected without sacrificing the bladder. The whole tumor was resected by performing low anterior resection (D3) and partial resection of the bladder. Subsequent pathological examination of the resected specimen indicated complete response to chemotherapy due to the absence of malignant cells. Because higher response rate is reported for modern chemotherapy, including targeted therapy, preoperative intensive chemotherapy is an option for the local treatment of advanced rectal cancer. Downstaging chemotherapy is expected to enhance the role of function-preserving surgery for T4 rectal cancer.

Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Combined Modality Therapy; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Rectal Neoplasms

Case 1: A 69-year-old man was diagnosed with rectal cancer and liver metastasis. After low anterior resection, mFOLFOX6 plus cetuximab therapy was started for resection of the liver metastasis. However, he had to forgo liver resection because he developed acute exacerbation of interstitial pneumonitis (IP) after 6 courses of chemotherapy. Despite beginning the second-line treatment with mFOLFOX6 plus bevacizumab, he died in June 2012. Case 2: A 71-year-old man had undergone sigmoidectomy for sigmoid colon cancer in 2005, and right lower lobe partial resection for metastatic lung cancer in 2006. Although radiofrequency ablation or transcatheter arterial chemoembolization had been performed for multiple liver metastases several times since 2007, his multiple liver metastases were uncontrollable. Therefore, FOLFOX4 therapy was started in 2010, and mFOLFOX6 plus cetuximab therapy was substituted for FOLFOX4 therapy in 2011. The patient died in March 2012 due to the rapid development of IP, and thus, it appears that IP was the cause of death in both patients. The general condition, including pulmonary function, of patients at risk of IP must be checked before starting cetuximab therapy for metastatic colorectal cancer.

Topics: Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Cetuximab; Fatal Outcome; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Diseases, Interstitial; Male; Neoplasm Staging; Organoplatinum Compounds; Rectal Neoplasms

An approximately 50-year-old man with rectal cancer(RbP)[ cT3(cA), cN3, cM0, and cStage IIIb] who desired anus preservation was administered mFOLFOX6 therapy. This treatment decreased the size of both the tumor and the lymph node, and intersphincteric resection (ISR) was performed. Histopathology demonstrated tumor invasion beyond the muscularis propria, and the histological effectiveness was Grade 2. Because computed tomography showed an abscess in the dissection area, we performed postoperative drainage and the patient recovered. Therapy with mFOLFOX6 was repeated after the patient was discharged from hospital. Increased adoption of anus-preserving surgery is expected via successful control of local recurrence and distant metastasis by neoadjuvant chemotherapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Rectal Neoplasms

In 2006, a 70-year-old man who underwent low anterior resection for rectal cancer (SS, N0, H1, Stage IV)at a nearby hospital was referred to our hospital. He was noted to have multiple liver metastases of approximately 1 cm in diameter in S2, S3, S6, and S7, and was subsequently treated with chemotherapy for 5 courses of mFOLFOX6 regimen. He achieved a complete response radiographically. Thereafter, he underwent lateral segmentectomy of the liver and was noted to have residual tumor cells by histopathological examination of the resected tissue. Seven months after the hepatectomy, recurrence occurred in S6 and S7 and a new lesion in S8 was noted. He then underwent 12 courses of mFOLFOX6. As of June 2012, the patient is alive without recurrence. A prolonged survival may be possible if downstaging is achieved with successful chemotherapy. However, similar to the present case, the detection of residual cancer cells during histopathological examination of the resected tissues has been reported in the literature. Thus, further investigation is needed to determine the optimal treatment of cases achieving a radiographic complete response.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Fluorouracil; Hepatectomy; Humans; Leucovorin; Liver Neoplasms; Male; Neoplasm Staging; Organoplatinum Compounds; Radiography; Rectal Neoplasms

A 48-year-old man with respiratory discomfort was diagnosed with rectal cancer with carcinomatous lymphangiosis, together with lung and sternum metastasis. As the patient's performance status(PS) was 2, mFOLFOX6+bevacizumab (Bmab)therapy with a 20% reduction in the dose was started. Three courses of this treatment resulted in improved respiratory function, and his PS dropped to 1. A chest computed tomography(CT) scan taken after four courses of this treatment indicated that pleural effusion had almost disappeared, and that the shadow on the lung had also reduced. However, after 20 courses of this treatment the disease had progressed. The regimen was changed to irinotecan (CPT-11)+Bmab administration. All of these chemotherapeutic treatments were administered on an outpatient basis. Sixteen months after the diagnosis of rectal cancer, the patient died. In recent years, combination chemotherapy for unresectable colorectal cancer has become recognized as a standard regimen, though adverse effects frequently occur. Thus, intensive chemotherapy is not always recommended for patients with poor PS. In this report, we presented a case of pulmonary metastases from rectal cancer, carcinomatous lymphangiosis, and sternum metastasis that was successfully treated with mFOLFOX6+Bmab.

Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Bone Neoplasms; Fatal Outcome; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Rectal Neoplasms

This case concerns a 50-year-old male patient who was diagnosed with rectal cancer without any obvious distal metastasis. The patient underwent abdominoperineal resection of the rectum with lateral lymph node dissection exclusively on the lesion side. An obturator lymph node metastasis was found, and histopathological tests revealed that the patient was in Stage IIIb. FOLFOX4 therapy was performed as postoperative adjuvant chemotherapy, and although temporary discontinuation was necessary due to abscesses in the buttocks, the patient completed 10 courses of chemotherapy. Lung metastasis was diagnosed when a chest computed tomography revealed a nodule 12 mm in diameter immediately above the diaphragm in the left S8. Since the nodule was a solitary tumor, radiofrequency ablation (RFA) therapy was performed, after which postoperative adjuvant chemotherapy was changed to FOLFIRI therapy. No obvious adverse events occurred, making it possible to continue the therapy without withdrawal. The lesions tended to gradually shrink, and during the 50th course of the therapy, the patient converted from partial remission (PR) to complete remission (CR). The FOLFIRI therapy was continued for another 6 months and then suspended for a while. The patient received 62 courses of FOLFIRI therapy in total. No sign of recurrence has been found. This case demonstrates the successful treatment and CR of recurrent lung metastasis after surgery for rectal cancer using lung RFA therapy and long-term administration of FOLFIRI.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Catheter Ablation; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Rectal Neoplasms; Recurrence; Time Factors

This study investigated whether total mesorectal excision (TME), when carried out at the original operation for rectal cancer, influenced the effectiveness of subsequent salvage treatment for pelvic recurrence.. Between September 1990 and January 2006, 124 patients underwent radiotherapy and salvage surgery at the Norwegian Radium Hospital for locally recurrent rectal cancer without known distant metastases. Most of the primary operations had been performed at other hospitals: 62 patients had undergone a non-TME procedure (most operations in this group of patients were carried out before 1994); and 62 patients had undergone a TME procedure (all operations in this group of patients were carried out after 1992). In the TME group, 17 patients also received radiosensitizing chemotherapy.. A lower proportion of primary abdominoperineal resection and more sensitizing chemotherapy seemed to be to the advantage of the TME group, while a higher frequency of intra-operative radiotherapy might be beneficial in the non-TME group. The 5-year survival and R0 stage achievement were 30/24% and 44/40% for non-TME/TME groups. The local re-recurrence rates were nearly identical, at around 50%, for both groups. There was no change in R stage over time.. A primary operation which includes TME does not reduce the effectiveness of subsequent salvage treatment for locally recurrent rectal cancer.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Combined Modality Therapy; Digestive System Surgical Procedures; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Norway; Radiation-Sensitizing Agents; Rectal Neoplasms; Salvage Therapy; Survival Rate; Treatment Outcome; Vitamin B Complex

To assess the safety and efficacy of oxaliplatin (OXA) plus dual inhibition of thymidilate synthase during preoperative pelvic radiotherapy (RT) in patients with poor prognosis for rectal carcinoma.. Sixty-three patients with the following characteristics, a clinical (c) stage T4, cN1-2, or cT3N0 of ≤5 cm from the anal verge and/or with a circumferential resection margin (CRM) of ≤5 mm (by magnetic resonance imaging), received three biweekly courses of chemotherapy with OXA, 100 mg/m2; raltitrexed (RTX), 2.5 mg/m2 on day 1, and 5-fluorouracil (5-FU), 900 mg/m2 (31 patients) or 800 mg/m2 (32 patients); levo-folinic acid (LFA), 250 mg/m2 on day 2, during pelvic RT (45 Gy). Pathologic response was defined as complete pathological response (ypCR), major (tumor regression grade(TRG) 2 to 3, with ypCRM-ve and ypN-ve) or minor or no response (TRG4 to -5, or ypCRM+ve, or ypN+ve). Adjuvant 5-FU/LFA regimen was given in cases of cT4, ypN+ve, or ypCRM+ve.. Overall, neutropenia (40%) and diarrhea (13%) were the most common grade≥3 toxicities, and tolerability was better with a 5-FU dose reduction. No significant difference in pathologic response was seen according 5-FU dosage: overall, a ypCR was obtained in 24 (39%) patients, and a major response in 20 (32%) patients. The 5-year probability of freedom from recurrence was 80% (95% confidence interval, 68%-92%); it was 56% for the minor/no response group, while it was around 90% for both the ypCR and the major response group.. OXA, RTX, and 5-FU/LFA administered during pelvic RT produced promising early and long-term results in rectal carcinoma patients with poor prognosis. The postoperative treatment strategy applied in our study supports the risk-adapted approach in postoperative management.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Diarrhea; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Proteins; Neoplasm Staging; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Postoperative Complications; Preoperative Care; Prognosis; Quinazolines; Radiotherapy Dosage; Rectal Neoplasms; Remission Induction; Thiophenes; Thymidylate Synthase; Treatment Outcome; Vitamin B Complex

The aim of this study was to identify criteria for three-dimensional anorectal ultrasonography (3D-AUS) to assess the response of rectal cancer to chemoradiotherapy; the 3D-AUS results were compared with the histopathological findings of the resected specimen.. Thirty-five patients underwent 3D-AUS and were grouped according to the presence (GI; n = 19) or absence (GII; n = 16) of anal canal invasion. All patients received chemoradiotherapy, then underwent a second 3D-AUS. The response (complete, partial or insignificant and lymph node metastasis) was evaluated. Tumour length (cm) and volume (cm(3) ), length and volume regression percentage (%), distal length regression, and distance between the distal tumour edge and the proximal border of the internal anal sphincter were measured before and after chemoradiotherapy. All patients underwent surgery, and the 3D-AUS image was compared with the histopathological findings.. Before chemoradiotherapy, the average tumour length was similar in G1 and GII, but the volume differed significantly (P = 0.0408). The response was insignificant in seven (37%) patients, partial in 10 (53%) patients and complete in two (10%) patients in GI. The corresponding figures for GII were one (6%) patient, 12 (75%) patients and three (19%) patients (P = 0.0318). The agreement between pathological and post-chemoratherapy 3D-AUS findings was almost identical for the identification of residual tumour or complete response (κ = 1.0) and substantial for lymph node metastases (κ = 0.74). The mean distance to the internal anal sphincter was greater in GII. A sphincter-saving resection was performed in 2/19 patients in GI and in 14/16 patients in GII (P < 0.0001). The histopathological examination revealed a free distal margin.. 3D-AUS was shown to evaluate accurately the response to chemoradiotherapy, helping in the selection of patients for a sphincter-saving resection. The distance between the tumour and the internal anal sphincter was the most important parameter in this respect.

Topics: Adenocarcinoma; Aged; Anal Canal; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Dose Fractionation, Radiation; Endosonography; Female; Fluorouracil; Humans; Imaging, Three-Dimensional; Leucovorin; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Organ Sparing Treatments; Patient Selection; Rectal Neoplasms; Tumor Burden

Adjuvant chemotherapy in rectal cancer is not well defined.After neoadjuvant chemoradiation and surgery, at least a short period of treatment with 5-fluorouracil is recommended, and some investigators claim a more aggressive approach, in particular, for those patients with a high risk of systemic relapse. Nevertheless, there are few studies about adjuvant combination therapy tolerance and efficacy, and no randomized trials have been conducted comparing fluoropyrimidines versus combination therapy such as folinic acid plus 5-fluorouracil plus oxaliplatin(FOLFOX), considered the standard of care in stage IIIcolon cancer. We present an institutional series of risk adapted adjuvant therapy. Sixty evaluable patients who had received treatment with neoadjuvant fluoropyrimidine radiotherapy and surgery now received adjuvant fluoropyrimidines in the case of pT0-2N0 or oxaliplatin based combination in the case of pT3-4 or N+ . Overall, 33 patients experienced downstaging to pT2-0N0 (55%) and27 patients were restaged as pT3-4 or N+ (45%) after surgery. Local recurrence rate was 5% (three patients), one local and one local plus systemic in the adjuvant single agent group and one local plus systemic in the adjuvant FOLFOX group. Systemic relapse occurred in 14 patients(23.3%), five (15%) in the single-agent group and nine(33.3%) in the FOLFOX group. Disease-free survival at 3 years for patients in the good prognostic group(pT0-2N0) and poor prognostic group (pT3-4 or N+ ) were 78.7 and 62.2%, respectively. Severe diarrhoea was more frequent with fluoropyrimidines and neutropenia, mucositis and peripheral neuropathy were more common with FOLFOX. There were no toxic deaths. A risk-adapted adjuvant therapeutic decision is feasible with an acceptable safety profile even with the use of oxaliplatin based combinations. Three-year disease-free survival compares favourably with historical controls, especially in those patients with high risk factors for relapse.Phase III controlled trials are needed.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemotherapy, Adjuvant; Deoxycytidine; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Radiotherapy, Adjuvant; Rectal Neoplasms

This study investigated the effects of preoperative chemoradiotherapy (PCRT) and the prognoses of patients with mucinous rectal cancer compared with those with nonmucinous cancer.. We retrospectively reviewed the medical records of 368 patients who underwent curative resection after PCRT, between 2000 and 2006, for midrectal to lower-rectal adenocarcinoma. Mucinous cancers were present in 23 patients (6.3%) and nonmucinous cancers in 345. In each patient, clinical stage before chemoradiotherapy was compared with pathologic stage to evaluate the extent of downstaging. Survival and multivariate analyses were performed using clinicopathologic variables. The median follow-up period was 42 months (range, 4-105 months).. There was no difference in clinical stage between the groups. Although 58 patients (16.8%) in the nonmucinous group achieved pathologic complete responses (pCR), no mucinous group patient showed such a response. T-downstaging was more frequently observed in the nonmucinous than in the mucinous group (189 vs 7 [54.9% vs 30.4%], P = .03), but N-downstaging was similar in the 2 groups. The 5-year overall survival rate (OS) was significantly lower in the mucinous than in the nonmucinous group (64.8% vs 79.8%, P = .049). Multivariate analysis revealed that mucinous histotype was an independent (negative) prognostic factor for survival (hazard ratio, 2.36; 95% confidence interval, 1.05-5.3; P = .04).. Patients with mucinous rectal cancer experienced a lower rate of T-downstaging after PCRT and had a poorer prognosis than did patients with nonmucinous cancer.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemoradiotherapy; Deoxycytidine; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Medical Records; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Preoperative Care; Prospective Studies; Radiotherapy; Rectal Neoplasms; Retrospective Studies; Survival Rate; Treatment Outcome

Cetuximab is an agent approved as epidermal growth factor receptor (EGFR)-positive for unresectable advanced or recurrent colorectal cancer. A 58-year-old man with liver metastasis had relapsed after resection of rectal cancer. We treated him with cetuximab monotherapy as third-line chemotherapy after treatment failures with infusional 5-FU, LV and oxaliplatin (FOLFOX4 regi- men); and infusional 5-FU, LV and irinotecan(FOLFIRI regimen). The patient was administered cetuximab (400 mg/m² initial dose and 250 mg/m²/ week thereafter). After sixteen weeks of treatment, a computed tomography scan revealed reduced sizes of the liver metastases. The tumor response has still been maintained after thirty courses of treatment, and the chemotherapeutic response was evaluated as a partial response according to the Response Evaluation Criteria In Solid Tumor guidelines. The main toxicity was a grade 2 rash, but was manageable by topical steroid and moisturizing agent. We have added some review of the literature, and the cetuximab therapy is reported.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cetuximab; Drug Resistance, Neoplasm; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Rectal Neoplasms; Recurrence; Salvage Therapy

The patient was a 54-year-old male with a huge advanced rectal cancer tumor. Abdominal CT showed liver metastasis and local progressive cancer of the rectum measuring 13 × 9 × 7 cm in diameter, which invaded the urinary bladder and sacrum. We established a diagnosis of unresectable rectal cancer and then performed sigmoid colostomy. After 16 courses of FOLFOX4, abdominal CT revealed the liver metastases to have disappeared, and the large-sized advanced rectal cancer had also remarkably decreased in size. Consequently, the patient underwent a resection of the rectum while his bladder was preserved. For 2 years 10 months after surgery, no local recurrence or distant metastasis has been observed, and the patient has received no postoperative chemotherapy. FOLFOX may therefore be a useful preoperative chemotherapy for the patients with unresectable primary rectal cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Fluorouracil; Humans; Leucovorin; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Pelvis; Rectal Neoplasms; Tomography, X-Ray Computed

The circulating cell-free DNA (cfDNA) in plasma has been reported to be a marker of cancer detection. The aim of this study was to investigate whether the cfDNA has a role as response biomarker in patients receiving preoperative chemoradiotherapy (CRT) for rectal cancer.. Sixty-seven patients (median age 61 years; male/female 42/25) who underwent CRT for rectal cancer were evaluated. After tumor regression grade (TRG) classification was made, the patients were classified as having disease that responded (TRG 1-2) and that did not respond (TRG 3-5) to therapy. Plasma samples were obtained from patients before and after CRT. The cfDNA levels were analyzed by quantitative real-time polymerase chain reaction of β-globin. On the basis of the Alu repeats, the cfDNA was considered as either total (fragments of 115 bp, Alu 115) or tumoral (fragments of 247 bp, Alu 247). The association between the pre- or post-CRT levels and between variations during CRT of the Alu 247, Alu 115 repeat, and Alu 247/115 ratio (cfDNA integrity index) and the pathologic tumor response was analyzed.. The baseline levels of cfDNA were not associated with tumor response. The post-CRT levels of the cfDNA integrity index were significantly lower in responsive compared to nonresponsive disease (P = 0.0009). Both the median value of the Alu 247 repeat and the cfDNA integrity index decreased after CRT in disease that responded to therapy (P < 0.005 and P < 0.005, respectively) compared to disease that did not respond to therapy (P = 0.83 and P = 0.726, respectively). The results of the multivariable logistic regression analysis showed that only the cfDNA integrity index was significantly and independently associated with tumor response to treatment.. The plasma levels of the longer fragments (Alu 247) of cfDNA and the cfDNA integrity index are promising markers to predict tumor response after preoperative CRT for rectal cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carboplatin; Case-Control Studies; Chemoradiotherapy; DNA; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Pilot Projects; Real-Time Polymerase Chain Reaction; Rectal Neoplasms; Survival Rate; Treatment Outcome; Young Adult

Early identification of inadequate response to preoperative chemoradiotherapy (CRT) may spare rectal cancer patients the toxicity of ineffective treatment. We prospectively evaluated tumor response with (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) early in the course of preoperative CRT.. A total of 27 prospectively accrued patients with locally advanced rectal cancer (T(3-4)/N(1)) received preoperative CRT (5040 cGy + 5FU-based chemotherapy). Patients underwent PET scanning before and 8-14 days after commencement of CRT. Scans were interpreted using 3 standard parameters: SUV(max), SUV(avg), and total lesion glycolysis (TLG) as well as an investigational parameter: visual response score (VRS). Percent pathologic response was quantified as a continuous variable. All PET parameters were correlated with pathology. Pathologic complete/near-complete response was defined as ≥95% tumor destruction, suboptimal response as <95%. Statistical analysis was performed using the Wilcoxon rank sum test and receiver operating characteristic (ROC) curve analysis.. Of the 27 patients, 11 (41%) had pathologic complete/near-complete response; 16 (59%) had suboptimal response. SUV(max), SUV(avg), and TLG did not discriminate between responders and nonresponders. Visual response score (VRS) was statistically significantly higher for complete/near-complete responders than for suboptimal responders (65 vs. 33%, P = 0.02). Suboptimal responders were identified with 94% sensitivity and 78% accuracy using a VRS cut-off of 50%.. In this pilot study, FDG-PET at 8-14 days after the beginning of preoperative CRT was unsuccessful at predicting pathological response with enough accuracy to justify an early change in therapy.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Female; Fluorodeoxyglucose F18; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Positron-Emission Tomography; Preoperative Care; Prospective Studies; Radiopharmaceuticals; Rectal Neoplasms; Sensitivity and Specificity; Survival Rate; Treatment Outcome

Disseminated intravascular coagulation (DIC) is a complication that may be experienced by patients with solid tumors. The prognosis of solid tumors with DIC is much poorer than those without DIC. Although treatment of the underlying disease is critical for improvement of DIC, the efficacy and safety of chemotherapy in patients with DIC associated with colorectal cancer are not clear. A 50-year-old man with advanced rectal cancer and multiple liver metastases experienced DIC during third-line treatment with cetuximab plus irinotecan, following 5-fluorouracil, leucovorin, oxaliplatin (FOLFOX) plus bevacizumab and 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab. Combination chemotherapy consisting of FOLFOX plus bevacizumab was reintroduced. Although platelet and fresh-frozen plasma transfusions were required daily before chemotherapy, the patient's laboratory values improved after two cycles of chemotherapy, without severe toxicity. The patient was discharged, and FOLFOX plus bevacizumab has been continued on an outpatient basis without sign of recurrence of DIC as of December 2010 (4 months after initiation of chemotherapy). This case suggests that reintroduction of combination chemotherapy with FOLFOX plus bevacizumab is effective and feasible in patients with colorectal cancer with DIC and that chemotherapy may be a treatment option for such patients.

Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Disseminated Intravascular Coagulation; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Rectal Neoplasms

The patient was a 70-year-old male who had multiple lung metastases of rectal cancer. He was administered UFT(300mg/ day)and LV(75mg/day)after Hartmann operation for rectal cancer. He complained of fever and difficulty breathing after 2 courses of these medicines, and was admitted for UFT-and LV-induced interstitial pneumonitis. Treatment with methylpredni- solone(30mg/day)improved his symptoms and revealed radical findings. He was ready for discharge on the 10th day after treatment. Interstitial pneumonitis-induced UFT and LV is rare, but can lead to severe complications, which should be diagnosed and treated by corticosteroid as soon as possible.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Humans; Leucovorin; Lung Diseases, Interstitial; Lung Neoplasms; Male; Rectal Neoplasms; Tegafur; Tomography, X-Ray Computed; Uracil

The study aimed to identify the factors predictive for extreme unresponsiveness to neoadjuvant therapy for rectal cancer.. Ninety-six patients with rectal cancer received neoadjuvant therapy (41 were treated with radiotherapy and 55 with chemoradiotherapy) before surgery. Tumour response, downstaging, pathological complete response (pCR) and disease-free survival were evaluated.. Tumour response, downstaging and pCR occurred in 70 (72.9%), 47 (49.0%) and 14 (14.6%) patients, respectively. Univariate analyses showed that a large tumour size, T4 stage, elevated serum tumour markers, poor differentiation, radiotherapy alone and mucinous tumour were indicators of poor tumour response and/or downstaging. On multivariate analysis, chemoradiotherapy was found to be predictive for tumour response and downstaging, whereas mucinous type and T4 stage negatively affected tumour response. No variable was found to be associated with pCR, but poor differentiation and T4 stage together predicted extreme unresponsiveness with a high specificity and a high positive predictive value. Very poor disease-free survival was also observed in patients simultaneously carrying these phenotypes.. Neoadjuvant chemoradiotherapy is superior to radiotherapy alone in producing a response of rectal cancer. Unresponsiveness was most likely to occur in patients with poor differentiation and T4 disease.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Disease-Free Survival; Dose Fractionation, Radiation; Drug Resistance, Neoplasm; Female; Fluorouracil; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Multivariate Analysis; Neoadjuvant Therapy; Neoplasm Grading; Neoplasm Staging; Organoplatinum Compounds; Predictive Value of Tests; Radiotherapy, Adjuvant; Rectal Neoplasms; Treatment Outcome

A 71-year-old man with eosinophilia was given a diagnosis of poorly differentiated adenocarcinoma of the rectum. Further examination showed that it had invaded the bone marrow. He had disseminated intravascular coagulation (DIC) from disseminated carcinomatosis of the bone marrow after colostomy. Chemotherapy (mFOLFOX6) was successful and his eosinophil count, DIC score and tumor markers normalized. We were able to continue chemotherapy after 5 months from the outbreak of disseminated carcinomatosis of the bone marrow. It is said that disseminated carcinomatosis of the bone marrow has a poor prognosis, but we were able to obtain a good response in this case by chemotherapy.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Neoplasms; Carcinoma; Disseminated Intravascular Coagulation; Eosinophilia; Fluorouracil; Humans; Leucovorin; Male; Organoplatinum Compounds; Rectal Neoplasms

The aim of this study was to investigate efficacy and toxicity of a modified 5-fluorouracil (5-FU), folinic acid, oxaliplatin (mFOLFOX-4) regimen followed by infusional 5-FU concomitant with radiotherapy for curatively resected stage III rectum adenocarcinoma patients.. Between April 2005 and July 2009, 55 operated stage III rectum cancer patients were evaluated retrospectively. mFOLFOX-4 regimen (oxaliplatin 85 mg/m2 1st day, folinic acid 200 mg/m2 1st day, 5-FU 400 mg/m2 iv bolus 1st day, 5-FU 1600 mg/m2 46 hours continuous infusion) was applied every 2 weeks. After four courses of mFOLFOX-4, 50.4 Gy (1.8 Gy in 28 fractions) radiotherapy with continuous 5-FU 200 mg/m(2)/day by infusion pump were given. On completion of chemoradiation four more mFOLFOX-4 courses were given.. Median age of the patients was 54 years (range 23-73 years). Low anterior resection was performed in 37 (67.3%) and abdominoperineal resection in 16 (29.1%) . Ten (18.2%) patients were at stage IIIA, 24 (43.6%) at stage IIIB and 21 (38.2%) at stage IIIC. Planned chemotherapy cycles were completed in 92.7% of patients. Grades 3-4 toxicity included neutropenia (9.1%), febrile neutropenia (3.6%), anemia (3.6%), diarrhea (21.8%), neuropathy (9.1%), renal toxicity (3.6%), hepatotoxicity (5.5%). Median follow-up time was 30 (9-57) months. Local recurrence and distant metastasis was observed in 3 (5.5%) and 10 (18.2%) patients, respectively. Ten (18.2%) patients died during follow-up. Three years disease free survival and overall survival were 67.5% and 77.3%, respectively.. mFOLFOX-4 following chemoradiotherapy with continuous 5- FU infusion is an effective and well tolerated adjuvant treatment for stage III rectal carcinoma patients.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Chemotherapy, Adjuvant; Disease-Free Survival; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Rectal Neoplasms; Retrospective Studies; Young Adult

The finding that some rectal cancers respond to neoadjuvant chemoradiation is broadening new surgical options for the treatment of some of these tumors that, until now, required a total mesorectal excision. Nevertheless, a fine match between clinical and pathological response is required when planning conservative surgical approaches.. This study aims to prospectively validate the use of endoscopic ultrasound as a predictor of clinical and pathological tumor response in patients with locally advanced rectal cancer.. : This is an observational study of a cohort of patients undergoing chemoradiation followed by surgery.. This study was conducted at a tertiary medical center.. A total of 235 consecutive patients who underwent chemoradiation followed by surgery at a single institution during a 7-year period were included.. All tumors were staged and restaged at 4 to 6 weeks after neoadjuvant treatment. Downsizing and downstaging were calculated between the initial and posttreatment measures and correlated to the pathological stage. The accuracy of endoscopic ultrasound to predict response was determined.. Findings after chemoradiation showed T-downstaging in 54 patients (23%) and N-downstaging in 110 (47%). Overstaging occurred in 88 (37%) patients and was more commonly observed than understaging (21 patients; 9%). Related to the pathological report, endoscopic ultrasound correctly matched the T stage in 54% and the N stage in 75% of tumors. Sensitivity, specificity, and positive and negative predictive values to predict nodal involvement were 39%, 91%, 67%, and 76%. Accuracy was not influenced by such factors as age, distance of the tumor from the anal verge, or time to surgery.. This study was limited by the lack of comparison with other imaging methods.. Endoscopic ultrasound allows prediction of involved lymph nodes in 75% of the cases; however, 1 in 5 patients are missclassified as uN0 after neoadjuvant treatment. In our point of view, this percentage is too high to rely only on this diagnostic modality to support a "wait and see" approach.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Colonoscopy; Endosonography; Female; Fluorouracil; Humans; Leucovorin; Lymphatic Metastasis; Male; Neoadjuvant Therapy; Neoplasm Staging; Prospective Studies; Radiotherapy Dosage; Rectal Neoplasms; Sensitivity and Specificity; Treatment Outcome

Seven patients with rectal cancers which were difficult to ensure surgical margins for because of huge tumors(over 60mm in diameter), invasion to other organs, or severe nodal metastases, were treated with preoperative chemotherapy consisting of 2-10 courses of mFOLFOX6.The response rate was 85. 7%.Complete response was observed in one patient, and partial response was observed in 5 patients.Four to 5 weeks after chemotherapy, surgery was performed for all patients.Following surgical procedures, abdominoperineal resections were performed in 4 cases, low anterior resections in 3 cases, and removal of the liver metastases(not diagnosed preoperatively)in 2 cases.R0 resections were also performed in all patients. According to the histological regression grading of the resected specimens, one patient had a complete disappearance of tumor, 5 had grade 1a regression, and one had grade 1b regression.One of the 7 patients had recurrence at the lung. However, another patient survived without recurrence. In this study, preoperative mFOLFOX6 chemotherapy was expected to be an effective treatment for improving the curative resection rate of patients with tumors which were difficult to ensure surgical margins because of huge tumors, invasion to other organs, or severe nodal metastases.

Topics: Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Organoplatinum Compounds; Pilot Projects; Rectal Neoplasms

We report a case of synchronous multiple liver metastases of rectal cancer successfully treated with tegafur/uracil(UFT) and oral Leucovorin (LV) chemotherapy. Lower anterior resection was carried out on the rectal cancer patient (an 80-year- old man), who had synchronous multiple liver metastases. The UFT (450 mg/day) and oral LV (75 mg/day) were orally administered for 4 weeks, followed by a 1-week interval after the surgical procedure. After completion of 16 courses, CT scan showed no liver metastases, and the patient was judged to have achieved a complete response (CR). The interval of CR was maintained for sixteen months until the age of 82. This chemotherapy is expected to have a potent therapeutic efficacy for older adult patients with advanced rectal cancer, because it is convenient and causes no severe diverse events.

Topics: Administration, Oral; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Humans; Leucovorin; Liver Neoplasms; Male; Rectal Neoplasms; Tegafur; Tomography, X-Ray Computed; Uracil

The safety of regional hyperthermia has been tested in locally advanced rectal cancer. The aim of this study was to assess the effects of shorter distal margins on local control and survival in rectal cancer patients who were treated with preoperative hyperthermochemoradiation therapy (HCRT) and underwent rectal resection by using the total mesorectal excision (TME) method.. Ninety-three patients with rectal adenocarcinoma who received neoadjuvant HCRT (total radiation: 50 Gy) were included in this study. Surgery was performed 8 weeks after HCRT, and each resected specimen was evaluated histologically. Length of distal surgical margins, status of circumferential margins, pathological response, and tumor node metastasis stage were examined for their effects on recurrence and survival.. Fifty-eight (62.4%) patients had tumor regression, and 20 (21.5%) had a pathological complete response. Distal margin length ranged from 1 to 55 mm (median, 21 mm) and did not correlate with local recurrence (p=0.57) or survival (p=0.75) by univariate analysis. Kaplan-Meier estimates of recurrence-free survival and local recurrence for the <10 mm versus ≥10 mm groups were not significantly different. Positive circumferential margins and failure of tumors to respond were unfavorable factors in survival.. Distal resection margins that are shorter than 10 mm but are not positive appear to be equivalent to longer margins in patients who undergo HCRT followed by rectal resection with TME. To improve the down-staging rate, additional studies are needed.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Digestive System Surgical Procedures; Female; Fluorouracil; Follow-Up Studies; Gamma Rays; Humans; Hyperthermia, Induced; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Rectal Neoplasms; Survival Rate; Treatment Outcome

A 56-year-old woman was referred to our hospital because of melena. After examinations she was diagnosed with rectal cancer. Anterior resection was performed and the final diagnosis was Stage IIIa. She was treated with adjuvant chemotherapy consisting of UFT/Uzel for one year, followed by UFT alone for one year. Two years after the surgery, abdominal CT suggested solitary paraaortic lymph node metastasis. As the patient denied a surgical treatment, mFOLFOX6 chemotherapy was induced. However, the patient developed a grade 3 allergic side effect, FOLFIRI was administered. Six months after the chemotherapy was started, the paraaortic lymph node metastasis had disappeared. After 50 courses, the case was considered to have achieved a clinical CR which has been maintained now. FOLFIRI was effective for recurrent rectal cancer with paraaortic LN metastasis.

Topics: Antineoplastic Combined Chemotherapy Protocols; Aorta; Camptothecin; Female; Fluorouracil; Humans; Leucovorin; Lymphatic Metastasis; Middle Aged; Rectal Neoplasms; Recurrence; Remission Induction; Tomography, X-Ray Computed

The safety and usefulness of FOLFOX therapy for elderly patients with metastatic colorectal cancer have not been clarified yet. We report an extremely aged patient case of metastatic colorectal cancer that was treated successfully with modified FOLFOX6 (mFOLFOX6) plus bevacizumab therapy. An 85-year-old man was diagnosed as having a low rectal cancer with paraaortic and left inguinal lymph node involvement. He was given mFOLFOX6 therapy after sigmoid colostomy. Bevacizumab was added to mFOLFOX6 after the second course. Although he experienced grade 2 neurtropenia and grade 1 neurotoxicity, the maximal diameter of the metastatic lymph nodes was decreased to a normal diameter after 9 courses. The primary tumor also disappeared and the biopsy revealed no cancer cells. He remains free of recurrence for 12 months after the end of chemotherapy.

Topics: Aged, 80 and over; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Aorta; Bevacizumab; Fluorouracil; Humans; Leucovorin; Lymphatic Metastasis; Male; Organoplatinum Compounds; Rectal Neoplasms; Tomography, X-Ray Computed

We describe the case of a 74-year-old man with liver resection for originally unresectable liver metastasis from colorectal cancer after multiagent chemotherapy. Eleven bilobar liver metastases appeared four months after curative resection for double cancer of sigmoid colon and upper rectum. After 6 courses of multiagent chemotherapy (mFOLFOX 6 with bevacizumab), the number of liver metastasis decreased from 11 to 5. The patient underwent curative resection for liver metastasis. A new lesion of 7 mm in the segment 6 appeared 8 months after an initial liver resection. After 3 months' observation, two more liver metastases appeared. All liver metastases were resected. Solitary lung metastasis appeared 10 months after the second liver resection. The lung metastasis was also resected. The patient was alive with no evidence of disease in 33 months after the initial liver resection. We experienced the case with repeated liver resections after multiagent chemotherapy for originally unresectable bilobar liver metastasis. The therapeutic strategy which combines surgical resection with cytotoxic chemotherapy will be important more than ever.

Topics: Aged; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Combined Modality Therapy; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Neoplasm Staging; Neoplasms, Multiple Primary; Organoplatinum Compounds; Rectal Neoplasms; Sigmoid Neoplasms

A 69-year-old male was operated on sigmoidectomy for sigmoid colon cancer (SS, N2, H0, P0, M0, stage IIIb) 7 years ago. Two years later, he was diagnosed for rectal cancer and bilateral lung metastases by TBLB. We performed Mile's operation, and the rectal focus was pathologically diagnosed with a recurrence of sigmoid colon cancer. After surgery, chemotherapy with FOLFOX was started for bilateral lung metastases, resulting in CR during the 22 months. But bilateral lung metastases were exacerbated, and then we administered several other chemotherapies. Five years have passed since chemotherapy started, although the focuses tended to progress. Right now, he has been a chemotherapy outpatient for last 5 years.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Organoplatinum Compounds; Rectal Neoplasms; Recurrence; Sigmoid Neoplasms; Time Factors; Tomography, X-Ray Computed

To evaluate the efficacy of modified De Gramont (mDG) and FOLFOX4 (mFOLFOX4) regimens in patients with locally advanced rectal cancer (LARC).. Patients that received adjuvant chemotherapy (CT) for the treatment of LARC (stage II and III) were retrospectively evaluated.. A total of 231 patients were examined. Median age was 58 (range, 18-83) and, of these patients, 36 (15.6%) had stage II and 195 (84.4%) had stage III disease. While the patients with stage II disease received only mDG regimen (36, 100.0%), of the patients with stage III disease, 71 (36.5%) received mDG and 124 (63.5%) received mFOLFOX4 regimen. Patients with stage III disease showed recurrences more often, but this difference was not statistically significant. Similarly, for the patients with stage III disease, there was no statistically significant relation between the adjuvant CT regimen received and the rate of recurrence. In patients with stage II disease, who received mDG, median DFS was 101 months and median OS was 106 months. For the patients with stage III disease, the patients that received mDG showed a median DFS of 78 months and a median OS of 96 months, while the patients that received mFOLFOX4 had a median DFS of 51 months and a median OS of 78 months. Although, for the patients with stage III disease, there are major differences between the two different regimens of CT in terms of DFS and OS, this difference was not statistically significant.When the results were evaluated from the perspective of toxicity, the patients that received mFOLFOX4 showed more toxicity. Neurotoxicity, which was seen in the patients that were given mFOLFOX4, was the most prominent toxicity.. mDG and mFOLFOX4 regimens are applicable regimens as adjuvant CT for the treatment of LARC.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Chemotherapy, Adjuvant; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Maximum Tolerated Dose; Middle Aged; Neoadjuvant Therapy; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Prognosis; Rectal Neoplasms; Retrospective Studies; Survival Rate; Young Adult

The extent to which neoadjuvant chemoradiotherapy for rectal cancer influences postoperative morbidity is controversial. This study investigated whether this treatment suppresses the normal perioperative inflammatory response and explored the clinical implications.. Prospective databases were queried to identify 37 consecutive study patients undergoing definitive surgery following 5-FU/capecitabine-based chemoradiotherapy and 34 consecutive untreated control patients operated upon for rectal or rectosigmoid cancer. Preoperative (< 10 days) and postoperative (< 24 h) neutrophil counts, along with morbidity data, were confirmed retrospectively. Univariate and multivariate analyses assessed the apparent effect of chemoradiotherapy on change in neutrophil count. The latter's association with postoperative morbidity was then examined.. Sufficient data were available for 34 study and 27 control patients. Repeated-measures ANCOVA revealed significant differences between their perioperative neutrophil counts (P = 0.02). Of the other characteristics which differed between the groups, only age and tumour location were prognostically significant regarding perioperative change in neutrophil count. Accounting for relevant covariates, chemoradiotherapy was significantly associated with a suppressed perioperative neutrophil leucocytosis. Local postoperative complications affected 25 of 61 patients, who had lower perioperative neutrophil increases than their counterparts (P = 0.016).. Chemoradiotherapy appears to suppress the perioperative inflammatory response, thereby increasing susceptibility to local postoperative complications.

Topics: Aged; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Leukocytosis; Male; Middle Aged; Morbidity; Neoadjuvant Therapy; Neutrophils; Postoperative Complications; Radiotherapy, Adjuvant; Rectal Neoplasms; Treatment Outcome; Vitamin B Complex

Pelvic recurrent rectal cancer is still a challenging clinical problem, and patients generally have a dismal prognosis and a poor quality of life. Surgical resection represents the only potentially curative treatment; neoadjuvant treatments are presently being taken into consideration to increase the resectability rate and to improve long-term survival.. Among 157 patients observed with recurrent rectal cancer, a series of 58 patients who underwent surgical exploration with curative intent for isolated local recurrence at a single referral institution was retrospectively analyzed. Demographic, pathologic, and therapeutic factors were evaluated to assess long-term prognosis and local control.. Forty-four (75.9%) of 58 patients underwent surgical resection. The overall 5-year survival rate for patients who underwent surgical resection was 54.2%, whereas none of the unresected patients lived 5 years (P < 0.001). Patients with R0 resection showed a statistically higher 5-year overall survival and local control rate (72.4 and 70.2%, respectively) compared to R1 patients (37.5 and 31.2%, respectively). At multivariate survival analysis, feasibility of a surgical resection and radicality of excision proved to be independent positive prognostic factors. In contrast, increased presalvage carcinoembryonic antigen serum levels, back pain at diagnosis, and an increasing degree of fixation of recurrent disease to the pelvic wall at preoperative computed tomographic scan were statistically significantly linked to decreased overall survival. Preoperative chemoradiation and radicality of the surgical excision independently influenced the local control among surgically resected patients.. Surgical resection still remains the most important therapeutic and prognostic factor for patients with locally recurrent rectal cancer. Multimodal treatments can be safely performed by an experienced team in referral tertiary centers and can result in a safer outcome, better local disease control, and even long-term survival in carefully selected patients.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Pelvic Neoplasms; Prognosis; Rectal Neoplasms; Retrospective Studies; Surgical Procedures, Operative; Survival Rate

Acute abdominal symptoms with CT scan evidence of intramural gas in bowel walls (pneumatosis cystoides intestinalis, PCI) and of gas in the portal venous blood (PBG) in patients undergoing chemotherapy may represent a worrisome picture, suggestive of bowel necrosis. This picture remains a major clinical clue and the reporting of new cases may help to share awareness and experience on management. We describe a patient with acute abdominal symptoms and evidence of PCI with PBG under cetuximab, oxaliplatin, tegafur-uracil and folinic acid chemotherapy for metastatic adenocarcinoma of the rectosigmoid junction.. After admission for mucositis with diarrhea and profound dehydration, and subsequent emergency laparotomy for derotation of an intestinal volvulus, on the tenth postoperative day the patient developed fever and abdominal pain, with CT scan evidence of PCI with PBG. The exam of the abdomen did not suggest major problems requiring emergency surgery, and antibiotic treatment with close monitoring were performed, followed by rapid improvement.. Twelve days later, after resumption of oral diet, the patient unexpectedly suffered a spontaneous jejunal microperforation, requiring emergency laparotomy and bowel resection. Pathology showed that the perforation was within an area of ulceration involving the inner superficial layer of the bowel. Subsequently recovery was normal and at present, after 15 months, the patient is well and continuing chemotherapy.. This is probably the first report of PCI with PBG related to intestinal toxicity during cetuximab, oxaliplatin, tegafur-uracil and folinic acid chemotherapy in a patient with advanced rectal carcinoma, followed by delayed small bowel perforation. It provides an example of the challenges involved in the management of this type of patient.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Cetuximab; Gases; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Pneumatosis Cystoides Intestinalis; Portal Vein; Rectal Neoplasms; Tegafur

Long-term hemodialysis is considered to be a significant risk factor for cancer, but little is known about the use of oxaliplatin in patients on chronic hemodialysis. A 58-year-old man on chronic hemodialysis was treated for unresectable rectal cancer with synchronous hepatic metastasis by FOLFOX6 therapy with therapeutic drug monitoring. Plasma levels of total platinum, ultrafiltrate (free) platinum and 5-fluorouracil were monitored from the start of oxaliplatin administration to 120 h after the end of oxaliplatin infusion. Pharmacokinetic data of free platinum showed a bimodal pattern, decreased rapidly during the first dialysis and subsequently rose until 48 h after oxaliplatin infusion. The free platinum area under the curve was 15.7-18.9 microg h/ml when 40 mg/m(2) of oxaliplatin was administered, which was comparable to the area under the curve at 85 mg/m(2) in patient with normal renal function. The total platinum level reached a peak immediately before dialysis and gradually decreased. The 5-fluorouracil level decreased rapidly after the start of dialysis and remained constant during the continuous infusion of 5-fluorouracil. Tumor response was judged to be stable disease for >6 months, and no peripheral neuropathy or other toxicity was observed even after 11 courses. FOLFOX6 therapy with reduced dose of oxaliplatin had been safely performed for >6 months without any severe toxicity. The serum levels of free platinum showed bimodal pattern, and this second peak increased the area under the curve of free platinum. This pattern seems to be unique in patients on hemodialysis.

Topics: Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Chronic Disease; Drug Monitoring; Fluorouracil; Glomerulonephritis; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Rectal Neoplasms; Renal Dialysis

A 56-year-old man with abnormal chest X-P and stool occult bleeding was admitted. Colonoscopy detected rectal cancer and sigmoid al polyps. The biopsy results suggested that the rectal lesion was well- to moderately-differentiated adenocarcinoma and the sigmoidal polyp contained well -differentiated adenocarcinoma. CT scan revealed multiple lung, liver and lymph node metastasis. We judged the case to be inoperable and decided to start systemic chemotherapy (FOLFOX4). After treatment with chemotherapy, the tumor shrank and metastatic lesions disappeared. Low anterior resection was done, and final pathological examination revealed a complete response of the main tumor by treating with FOLFOX4.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Fluorouracil; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoadjuvant Therapy; Rectal Neoplasms

The aim of the present study was to compare the influence of preoperative chemoradiotherapy (CRT) with postoperative CRT on the incidence and types of postoperative complications in rectal cancer patients who underwent sphincter-saving resection.. We reviewed 285 patients who received preoperative CRT and 418 patients who received postoperative CRT between January 2000 and December 2006.. There was no between-group difference in age, gender, or cancer stage. In the pre-CRT group, the mean level of anastomosis from the anal verge was lower (3.5 +/- 1.4 cm vs. 4.3 +/- 1.7 cm, p < 0.001) and the rate of T4 lesion and temporary diverting ileostomy was higher than in the post-CRT group. Delayed anastomotic leakage and rectovaginal fistulae developed more frequently in the pre-CRT group than in the post-CRT group (3.9% vs. 1.2%, p = 0.020, 6.5% vs. 1.3%, p = 0.027, respectively). Small bowel obstruction (arising from radiation enteritis) requiring surgical intervention was more frequent in the post-CRT group (0% in the pre-CRT group vs. 1.4% in the post-CRT group, p = 0.042). Multivariate analysis identified preoperative CRT as an independent risk factor for fistulous complications (delayed anastomotic leakage, rectovaginal fistula, rectovesical fistula), and postoperative CRT as a risk factor for obstructive complications (anastomotic stricture, small bowel obstruction). The stoma-free rates were significantly lower in the pre-CRT group than in the post-CRT group (5-year stoma-free rates: 92.8% vs. 97.0%, p = 0.008).. The overall postoperative complication rates were similar between the pre-CRT and the Post-CRT groups. However, the pattern of postoperative complications seen after sphincter- saving resection differed with reference to the timing of CRT.

Topics: Adenocarcinoma; Adult; Aged; Anal Canal; Anastomosis, Surgical; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Deoxycytidine; Drug Administration Schedule; Enteritis; Female; Fluorouracil; Humans; Ileostomy; Intestinal Obstruction; Korea; Leucovorin; Male; Middle Aged; Multivariate Analysis; Neoadjuvant Therapy; Postoperative Complications; Preoperative Care; Radiotherapy Dosage; Rectal Fistula; Rectal Neoplasms; Rectovaginal Fistula; Rectum; Urinary Bladder Fistula; Young Adult

The patient was a 55-year-old female who had multiple liver metastases of rectal cancer. This patient underwent hepatic arterial infusion chemotherapy after low anterior resection for rectal cancer. Hepatic arterial infusion was discontinued due to severe diarrhea, and the administration of UFT (300 mg/day) and LV(75 mg/day) was then begun. The carcinoembryonic antigen (CEA) level was normalized immediately after the start of this administration. One year later, liver metastases disappeared on computed tomography (CT) and a complete response (CR) was achieved. No adverse events were noted, and CR was maintained for 2 years. This therapy can serve as one of the chemotherapies for advanced colorectal cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Leucovorin; Liver Neoplasms; Magnetic Resonance Imaging; Middle Aged; Neoplasm Staging; Rectal Neoplasms; Remission Induction; Tegafur; Tomography, X-Ray Computed; Uracil

Angiogenesis plays an important role in tumor progression. The vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis. In the present study we evaluated single nucleotide polymorphisms (SNPs) -2578C > A, -1154G > A, and +936C > T in the VEGF gene, and their prognostic value for patients operated on for colorectal cancer (CRC).. VEGF polymorphisms have been analyzed in 177 patients who had undergone surgical resection at Hospital Clínico San Carlos. The analysis of these polymorphisms was performed with specific probes for each nucleotide in a multiplex reaction using real-time PCR.. We only found a statistically significant relationship for one of these three polymorphisms, +936C > T, with gender and tumor location; 10.7% of patients heterozygotes for this SNP had tumors located in proximal colon, 35.2% in distal segment and 54.1% in rectum (p = 0.03). Patients with the +936T/T genotype had 100% overall survival (OS).. Patients with a +936T/T genotype showed increased survival, therefore the +936C > T SNP could be a useful marker in the follow-up and clinical management of patients with colorectal cancer.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Colectomy; Colonic Neoplasms; Combined Modality Therapy; Female; Fluorouracil; Genetic Predisposition to Disease; Genotype; Humans; Leucovorin; Male; Middle Aged; Neoplasm Proteins; Neovascularization, Pathologic; Polymorphism, Single Nucleotide; Prospective Studies; Rectal Neoplasms; Survival Analysis; Vascular Endothelial Growth Factor A

Fundamental research identified new therapy targets implicated in tumor proliferation and angiogenesis which lead to the development of several targeted therapies. Currently, three drugs are used in the treatment of advanced colorectal cancer, cetuximab and panitumumab, two anti epidermal growth factor receptor, and bevacizumab, an anti vascular endothelial growth factor.. We evaluated a treatment with oxaliplatin-based chemotherapy (Folfox7 regimen) and bevacizumab in patients with locally advanced and/or metastatic colorectal cancer. Objectives of the study are the evaluation of the efficacy, toxicity, progression free survival, overall survival and tumor cell expression of the vascular endothelial growth factor by immunochemistry.. 47 patients are included in the study during the period between April 2005 and June 2007; 28 men and 19 women. After six cycles of treatment, we achieved 67.3% of objectives responses and 76% of tumor control. The median progression free survival evaluated was 12 months (9.3-14.6 months) and median overall survival 18 months (9-26.9 months). The immunochemistry study of 46 tumours of the study achieved the following results: 13% (0), 17.4% (1+), 23.9% (2+) and 45.7% (3+). A correlation between the vascular endothelial growth factor expression, therapeutic responses and survival has been demonstrated but the difference was not significant in term of survival. Both chemotherapy toxicity and bevacizumab related toxicity are acceptable in our study.. The fact that vascular endothelial growth factor expression is common in more than 80% of colorectal cancers, lead to recommend the systematic use of bevacizumab with chemotherapy in the treatment of advanced colorectal cancer.

Topics: Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colonic Neoplasms; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Proteins; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms; Vascular Endothelial Growth Factors; Young Adult

To determine the radiologic downstaging and histological response after neo-adjuvant concurrent chemoradiation in locally advanced rectal cancers.. Case series.. Radiation Oncology department of Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, from December 2004 to November 2005.. Thirty patients with histopathologically confirmed locally advanced carcinoma rectum who had not received any treatment (chemotherapy, radiotherapy or surgery) prior to presentation were enrolled. Radiation therapy was delivered with a three-field technique to a dose of 50.4 Gy over 5 weeks at the rate of 1.8 Gy/day. Two cycles of chemotherapy were given synchronously, which comprised of 5-fluorouracil 350 mg/m2 and folinic acid 20 mg/m2 continuous intravenous infusion over first five days and last five days of radiotherapy. Surgery was planned 4-6 weeks later to chemoradiation after radiologic post therapy staging. Viable specimens were identified and toxicity was observed.. All patients completed treatment without modification. Radiologic downstaging was found in 56.7%, stable disease was seen in 30.0% and progressive disease was present in 13.3% of the patients. Radiologically complete resolution of tumour was not observed. Pathological complete resolution of tumour was achieved in 3.3% and near complete resolution was observed in 13.3% of the patients. In 86.6% cases, a total gross tumour resection with no macroscopic residual disease was possible. All the patients tolerated the treatment well.. Neo-adjuvant chemoradiation for locally advanced rectal cancers is associated with high resectability rate and is relatively safe with acceptable morbidity which favours its use in future.

Topics: Chemotherapy, Adjuvant; Fluorouracil; Humans; Immunosuppressive Agents; Infusions, Intravenous; Leucovorin; Neoadjuvant Therapy; Radiotherapy Dosage; Radiotherapy, Adjuvant; Rectal Neoplasms; Vitamin B Complex

We report a case of pathologically complete response of multiple liver metastases from rectal cancer after neoadjuvant chemotherapy. The patient was a 74-year-old woman who had advanced rectal cancer with synchronous liver metastases (T4N1M1). Following resection of the primary tumor, she received biweekly mFOLFOX6 plus bevacizumab neoadjuvant chemotherapy. After 5 courses, the liver tumors were markedly reduced in size. Three weeks after the final treatment, she underwent partial hepatectomies. Histologically, no cancer cells were detected in any resected specimens. The postoperative course was uneventful, and she has been well without recurrence for one year at the time of writing. Regimens containing bevacizumab may result in good tumor response. Surgical resection is crucial for proof of pathologically complete response.

Topics: Adenocarcinoma; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Organoplatinum Compounds; Rectal Neoplasms

Although neoadjuvant chemoradiotherapy (CRT) is the standard treatment for advanced rectal cancer (RC), markers to predict the treatment response have not been fully established. In 73 patients with advanced RC who underwent CRT in a neoadjuvant setting, we retrospectively examined the associations between the clinical effects of CRT and blood cell counts before and after CRT. Clinical or pathological complete response (CR) was observed in 10 (14%) cases. The CR rate correlated significantly with the size and the circumferential extent of the tumor. Hemoglobin level, white blood cell (WBC) count and platelet count before CRT did not show a significant difference between CR and non-CR cases. Interestingly, however, lymphocyte ratio in WBC was significantly higher (p = 0.020), while neutrophil ratio tended to be lower (p = 0.099), in CR cases, which was shown to be an independent association by multivariate analysis. When all the blood data obtained in the entire treatment period were evaluated, circulating lymphocyte count was most markedly decreased in the CRT period and gradually recovered by the time of surgery, while the numbers of neutrophils and monocytes were comparatively stable. Moreover, the lymphocyte percentage in samples obtained from CR patients was maintained at a relatively higher level than that from non-CR patients. Since tumor shrinkage is known to be dependent not only on the characteristics of tumor cells but also on various host conditions, our data raise the possibility that a lymphocyte-mediated immune reaction may have a positive role in achieving complete eradication of tumor cells. Maintenance of circulating lymphocyte number may improve the response to CRT in rectal cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Drug Combinations; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Lymphocyte Count; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Radiotherapy, Adjuvant; Rectal Neoplasms; Retrospective Studies; Survival Rate; Tegafur; Treatment Outcome; Uracil

A 7 0-year-old man with multiple liver metastases from rectal cancer was admitted to our hospital. From imaging inspection, a resection was determined to be difficult, so he was treated with FOLFOX4 therapy. After ten courses of FOLFOX4, the liver metastases showed 52% reduction in size and were judged to be PR. Therefore low anterior resection of the rectum, left lobectomy of the liver and partial resection of the liver(S7, S8)were performed. He was able to undergo curative surgery after FOLFOX4 therapy.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Neoadjuvant Therapy; Organoplatinum Compounds; Rectal Neoplasms; Tomography, X-Ray Computed

An 80-year-old female visited our hospital with the chief complaint of lower abdominal pain and diarrhea. She was diagnosed to have rectal cancer. Hartmann operation was performed and curative resection was successfully achieved. Postoperative stage was III according to the classification of the Japanese Society for Cancer of the Colon and Rectum(The 7th Edition). She was treated with oral tegafur(UFT 300mg/body/day)as adjuvant chemotherapy for 6 months. Paraaortic lymph node metastasis and local recurrence were diagnosed by abdominal CT 1 year after the surgery. Her performance status score was 0. She was treated with modified FOLFOX6 chemotherapy combined with bevacizumab. Abdominal CT revealed a partial response after 5 courses. She experienced grade 2 leukocyopenia, grade 3 neutropenia, grade 2 proteinuria and grade 2 hypertension.

Topics: Aged, 80 and over; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Female; Fluorouracil; Humans; Leucovorin; Organoplatinum Compounds; Rectal Neoplasms; Recurrence; Tomography, X-Ray Computed

Adverse events associated with bevacizumab (BV) were haemorrhage, impaired wound healing and arterial thromboembolism. We report 2 patients with colorectal cancer who underwent percutaneous coronary intervention (PCI) for unstable angina soon after administration of chemotherapy including BV. CASE 1: A 74-year-old male with rectal cancer and simultaneous liver metastases was admitted to our hospital for unstable angina. Before admission he had received 4 courses of chemotherapy including BV. He had no coronary risk factors besides old age. Since coronary angiography (CAG) revealed significant stenosis in the mid-left circumflex coronary artery, PCI with a coronary stent was performed without any complications. CASE 2: A 67-year-old male with colon cancer and liver and lung metastases was referred to our Dept. of Internal Medicine for unstable angina. Before referral, he had undergone 28 courses of chemotherapy including BV. He had a history of familial hyperlipidemia and smoking. Since CAG revealed significant stenoses in the proximal left anterior descending coronary artery, PCI with coronary stents was performed without any complications. These 2 patients had no angina after PCI. PCI with coronary stent was safely performed in this patient with unstable angina soon after administration of chemotherapy including BV.

Topics: Aged; Angina, Unstable; Angiogenesis Inhibitors; Angiography; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colonic Neoplasms; Electrocardiography; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Organoplatinum Compounds; Rectal Neoplasms

Tumor response of rectal cancer to preoperative chemoradiotherapy (CRT) varies considerably. In experimental tumor models and clinical radiotherapy, activity of particular subsets of kinase signaling pathways seems to predict radiation response. This study aimed to determine whether tumor kinase activity profiles might predict tumor response to preoperative CRT in locally advanced rectal cancer (LARC).. Sixty-seven LARC patients were treated with a CRT regimen consisting of radiotherapy, fluorouracil, and, where possible, oxaliplatin. Pretreatment tumor biopsy specimens were analyzed using microarrays with kinase substrates, and the resulting substrate phosphorylation patterns were correlated with tumor response to preoperative treatment as assessed by histomorphologic tumor regression grade (TRG). A predictive model for TRG scores from phosphosubstrate signatures was obtained by partial-least-squares discriminant analysis. Prediction performance was evaluated by leave-one-out cross-validation and use of an independent test set.. In the patient population, 73% and 15% were scored as good responders (TRG 1-2) or intermediate responders (TRG 3), whereas 12% were assessed as poor responders (TRG 4-5). In a subset of 7 poor responders and 12 good responders, treatment outcome was correctly predicted for 95%. Application of the prediction model on the remaining patient samples resulted in correct prediction for 85%. Phosphosubstrate signatures generated by poor-responding tumors indicated high kinase activity, which was inhibited by the kinase inhibitor sunitinib, and several discriminating phosphosubstrates represented proteins derived from signaling pathways implicated in radioresistance.. Multiplex kinase activity profiling may identify functional biomarkers predictive of tumor response to preoperative CRT in LARC.

Topics: Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Combined Modality Therapy; Deoxycytidine; Female; Fluorouracil; Humans; Indoles; Least-Squares Analysis; Leucovorin; Male; Middle Aged; Neoplasm Proteins; Organoplatinum Compounds; Oxaliplatin; Phosphorylation; Phosphotransferases; Pyrroles; Radiation Tolerance; Rectal Neoplasms; Rectum; Remission Induction; Signal Transduction; Substrate Specificity; Sunitinib; Treatment Outcome

The patient was a 55-year-old man who complained of lower abdominal pain and fever, and was admitted to an emergency clinic. His diagnosis was rectal perforation combined with intraperitoneal abscess. Because his condition was in the preseptic state, an emergency operation was performed for colostomy and abscess drainage. After operation, he was diagnosed with rectal cancer colonoscopically. He refused reoperation and selected an oral chemotherapy regimen (UFT+LV therapy). 18 months later, he underwent Hartmann's operation. Histologically, cancer cells were absent. Complete response to chemotherapy was confirmed. He is free from any sign of recurrence until now.

Topics: Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Colostomy; Combined Modality Therapy; Humans; Leucovorin; Male; Middle Aged; Rectal Neoplasms; Remission Induction; Tegafur; Tomography, X-Ray Computed; Uracil

The aim of this study was to evaluate the feasibility of en bloc colorectal resection combined with radical prostatectomy as an alternative to total pelvic exenteration (TPE) for patients with locally advanced rectal cancer involving the lower urinary tract organs.. Twenty men with primary rectal cancer clinically involving the lower urinary tract organs underwent extended colorectal resection combined with radical prostatectomy. Data were entered prospectively into a database. Oncological and functional outcomes were analyzed.. Anal sphincter-preserving operation (SPO) with radical prostatectomy was performed in 12 patients, abdominoperineal resection with radical prostatectomy in 8, and urinary reconstruction in 16. Morbidity and mortality rates were 35.0% and 0%, respectively. Five-year overall and disease-free survival rates were 83.6% and 42%, respectively. The cumulative 5-year local recurrence rate was 20.0%. All patients with urinary reconstruction achieved good voiding function, and patients with SPO showed acceptable anal function.. For lower rectal cancers involving lower urinary tract, en bloc rectal resection combined with radical prostatectomy appears oncologically acceptable and can reduce the number of TPEs.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Feasibility Studies; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Organ Preservation; Plastic Surgery Procedures; Postoperative Complications; Prognosis; Prospective Studies; Prostatectomy; Prostatic Neoplasms; Radiotherapy Dosage; Rectal Neoplasms; Survival Rate; Urinary Bladder Neoplasms

The patient was a sixty-five-year-old man who had an advanced rectal cancer (Ra, type 2) with liver metastases. Low anterior resection with lymphnode dissection (D3) was done, but hepatectomy was not performed because of the multiple metastases besides the five tumors detected preoperatively. The pathological finding was moderately-differentiated adenocarcinoma. He was treated with 5-FU via the hepatic artery, but the therapy failed due to catheter infection after 3 postoperative months. Then, he received general 5-FU/l-LV therapy intravenously from 3 to 8 months after the operation, and oral UFT/LV (Uzel®) from 9 to 22 months. Next, we switched to single UFT therapy at 23 months because CT findings showed remarkable calcification in the liver metastases. But only one tumor of the liver (S6) among liver metastases enlarged at 27 months. We switched the chemotherapy again to UFT/Uzel and mFOLFOX6, but decided to perform hepatectomy of S6/7 at 39 months since it proved ineffective. The pathological finding was 90% necrosis and calcification of the tumor. Metastasis of the right 10th rib was newly found and was removed at 63 months after the first operation. Now, NC in the liver is continued 67 months after the first operation, and the patient is doing well.

Topics: Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Hepatectomy; Humans; Leucovorin; Liver Neoplasms; Male; Neoplasm Staging; Rectal Neoplasms; Tegafur; Tomography, X-Ray Computed; Uracil

Preoperative chemoradiotherapy (CCRT) followed by radical resection is an option for advanced low rectal cancer. This study was aimed to clarify the impact of CCRT on patients' outcome.. One hundred thirty-six patients with rectal cancer (<10  cm from anal verge) were enrolled prospectively between July 2000 and December 2004. The preoperative clinical stage was T3, T4, or node-positive disease. Sixty-nine and 67 patients underwent surgery with and without preoperative CCRT, respectively. The regimen of pre-op CCRT was a radiation dosage of 45  Gy in 20 fractions and oral tegafur-uracil (UFUR) and leucovorin.. There was no statistical difference in the preserved anorectal function between two groups after 5 years of follow-up (62.3% vs. 47.8%; P = 0.125). The 5-year overall survival and disease-free survival (DFS) percentage were 88.4% and 76.8% for patients with preoperative CCRT, and 65.7% and 58.2% for patients without CCRT, respectively. Patients with preoperative CCRT had a higher overall survival rate and DFS (P = 0.001 and 0.015).. In patients with advanced low rectal cancer, preoperative CCRT followed by radical surgery significantly improved overall survival and DFS compared with surgery alone. The effect of sphincter preservation with preoperative CCRT is questionable.

Topics: Adenocarcinoma; Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Humans; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Preoperative Care; Prognosis; Prospective Studies; Radiotherapy Dosage; Rectal Neoplasms; Survival Rate; Tegafur; Uracil

Combination of bevacizumab and FOLFIRI has currently become one of the standard therapeutic regimens. However, published information is still limited. The objective of the present retrospective observational study is to analyse the response and toxicity of first-line treatment with FOLFIRI+bevacizumab in patients with metastatic colorectal cancer (mCRC).. Data were collected from patients from nine Spanish sites diagnosed with mCRC, ECOG≤2, whose first treatment for advanced disease was at least three cycles of FOLFIRI+bevacizumab.. A total of 95 patients were enrolled into the study: 64.2% males, median age of 59 years (53.2-67.1 years), ECOG=0-1 in 96.9% of patients. The main site of primary tumour was the colon (69.7%), and most metastases occurred in the liver (71.6%). Clinical benefit was detected in 67.4% (57.0-76.6; 95% confidence interval (CI)), with 8.4% of CR and 42.1% of PR. Median TTP was 10.6 months (10.0-11.3; 95% CI), PFS was 10.6 months (9.8-11.3; 95% CI), and OS was 20.7 months (17.1-24.2; 95% CI). Main grade I-II toxicities included haematological toxicity (35.8%), diarrhea (27.3%), mucositis (25.3%), asthenia (19.0%), haemorrhages (11.6%), and emesis (10.6%). Toxicities reaching grades III-IV were haematological toxicity (9.5%), diarrhea (8.5%), mucositis (5.3%), hepatic toxicity (2.1%), asthenia (2.1%), proteinuria (1.1%), emesis (1.1%), pain (1.1%), and colics (1.1%).. Results of this study support the beneficial effect of adding bevacizumab to FOLFIRI regimen in terms of efficacy and show a favourable tolerability profile.

Topics: Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colonic Neoplasms; Colorectal Neoplasms; Disease Progression; Drug Tolerance; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Rectal Neoplasms; Retrospective Studies; Safety; Spain; Treatment Outcome

To evaluate whether expression of L-type amino acid transporter 1 (LAT1) in pretreatment rectal cancer biopsies is predictive of tumour response to neoadjuvant hyperthermo-chemoradiotherapy (HCRT).. Forty-four patients with rectal adenocarcinoma who received neoadjuvant HCRT were investigated. LAT1 expression was immunohistochemically evaluated using pretreatment biopsies. The operation was performed after 2-3 months following HCRT and each resected specimen was graded by the histological criteria of the Japanese Classification of Colorectal Carcinoma.. A positive LAT1 expression was recognized in 50.0% (22/44) of patients. Resected specimens were divided into 2 groups according to the histological grading criteria: good response (n=29) and poor response (n=15). LAT1-negative tumours had an 81.8% probability of good response and 18.2% probability of poor response. LAT1 expression showed marginally significant association with response to HCRT (p=0.05).. LAT1 may be a useful predictive marker of response to HCRT in rectal cancer.

Topics: Adenocarcinoma; Adult; Aged; Biopsy; Cell Membrane; Fluorouracil; Humans; Hyperthermia, Induced; Large Neutral Amino Acid-Transporter 1; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Predictive Value of Tests; Radiotherapy; Rectal Neoplasms; Treatment Outcome

Most colorectal cancer patients with liver metastases are not resectable upon initial diagnosis. Recently, chemotherapy improves overall survival of initially unresectable patients by allowing tumor downstaging and complete resection. We report a FOLFOX-refractory rectal cancer patient with unresectable multiple liver metastases, whose tumors could be downstaged and completely resected after initiation of FOLFIRI with cetuximab.. A 41-year-old male demonstrated rectal cancer with unresectable multiple liver metastases. He was treated by FOLFOX4 therapy as first-line chemotherapy. After initiating 14 courses, he was treated by FOLFIRI with cetuximab because of disease progression. After initiation of chemotherapy, radiographic examination demonstrated remarkable reduction of primary rectal tumor and metastatic liver tumors. He underwent complete rectal tumor resection after 13 courses of chemotherapy, and metastatic liver tumor resection after 18 courses of chemotherapy.

Topics: Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cetuximab; Drug Resistance, Neoplasm; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Organoplatinum Compounds; Rectal Neoplasms

A 62-year-old man had undergone anterior resection of rectum for rectosigmoid colon cancer with liver metastases. Postoperatively, the FOLOFOX6 regimen was performed in three courses. Metastatic liver tumors showed progressive disease(PD) on CT scan. The treatment was then changed to the FOLFIRI regimen for three courses. Metastatic liver tumors showed a partial response(PR)on CT scan. After six courses of the FOLFIRI regimen, the patient was given seven courses of the FOLFIRI +BV regimen. Hepatic resection of S2, S3, S4 and S6 segment was performed. The histological effect of chemotherapy was complete response(CR).

Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Rectal Neoplasms; Treatment Outcome

Complete tumor regression may develop after neoadjuvant chemoradiation therapy for distal rectal cancer. Studies have suggested that selected patients with complete clinical response may avoid radical surgery and close surveillance may provide good outcomes with no oncologic compromise. However, definition of complete clinical response is often imprecise and may vary between different studies. The aim of this study is to provide a clear definition for a complete clinical response after neoadjuvant chemoradiation therapy in patients with distal rectal cancer in addition to actual endoscopic videos from patients managed nonoperatively.. Patients with nonmetastatic distal rectal cancer treated by neoadjuvant chemoradiation therapy, including 50.4 Gy and concomitant 5-fluorouracil and leucovorin, were assessed for tumor response at least 8 weeks after chemoradiation therapy completion. Complete and incomplete clinical responses were defined based on clinical and endoscopic findings. Patients with complete clinical response were not immediately operated on and were closely followed. Early and late endoscopic findings were recorded.. Definition of a complete clinical response should be based on very strict clinical and endoscopic criteria. The finding of any residual superficial ulceration, irregularity, or nodule should prompt surgical attention, including transanal full-thickness excision or even a radical resection with total mesorectal excision. Standard or incisional biopsies should be avoided in this setting. Complete clinical responders should harbor no more than whitening of the mucosa, teleangiectasia with mucosal integrity to be considered for a nonoperative approach. In the presence of these findings, regularly scheduled reassessments may provide a safe alternative to these patients with early detection of recurrent disease.. Strict definition of the clinical and endoscopic findings of patients experiencing complete clinical response after neoadjuvant chemoradiation therapy may provide a useful tool for the understanding of outcomes of patients managed with no immediate surgery allowing standardization of classifications and comparison between the experiences of different institutions.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents; Endoscopy, Gastrointestinal; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Radiotherapy Dosage; Rectal Neoplasms; Treatment Outcome

Combined chemotherapy including 5-FU plus radiation treatment resulted in a synergistic effect has been reported. S-1 enhances a radiation response of colon cancer cell line xenografts. Also the effectiveness of S-1 + radiation therapy has been reported. A 66-year-old man underwent a low anterior resection for lower rectal cancer. Adjuvant chemotherapy was not performed due to Stage II rectal cancer. Twenty months after the operation, solitary sacral bone metastasis was found during the postoperative work-up. S-1 (120 mg/day) combined with radiotherapy was performed on days 1-14 and 21-35. Radiation (3 Gy) was administered a total of 45 Gy on days 1-5, 7-12 and 35-40. Moreover, the reduction was judged as complete response after 11 courses of mFOLFOX 6. There has been no sign of recurrence for 44 months. It suggested that local control therapy (S-1 + radiation) plus systemic chemotherapy (mFOLFOX6) was one of the promising effective therapies for single sacral bone metastasis of rectal cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Combined Modality Therapy; Drug Combinations; Fluorouracil; Humans; Leucovorin; Male; Organoplatinum Compounds; Oxonic Acid; Radiotherapy Dosage; Rectal Neoplasms; Sacrum; Tegafur

The advancement of systemic chemotherapy for colorectal carcinoma has improved a clinical response rate and expanded a possibility of resection, which we thought we could not have been operable at the initial visit. It also improved a prognosis of patients. We report here a case with liver resection of metastasis from rectal cancer followed by bevacizumab treatment.

Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Fluorouracil; Hepatectomy; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Rectal Neoplasms; Reoperation

Cetuximab (Erbitux) is a targeted therapy that used to treat metastatic colorectal cancer. It is classified as a "monoclonal antibody" and "signal transduction inhibitor" by binding to epidermal growth factor receptors (EGFR). We report 6 patients who responded well to cetuximab out of 8 patients with recurrent/advanced colorectal cancer who have received the drug at our hospital since November 2008. Four patients were men and 2 were women, with their ages ranging from 48 to 77 years. The primary cancers were located in the rectum (n=1), sigmoid colon (n=4), and ascending colon (n=1). Performance status (PS) was 0-1. These patients were treated with cetuximab as second-line (n=1), third-line (n=3), fifth-line (n=1), or seventh-line (n=1) therapy. Three patients received cetuximab monotherapy, while the other 3 were given CPT-11 (150 mg/m2, every 2 weeks) as concomitant therapy. Among the 3 patients receiving combination therapy, 2 patients had already received treatment with FOLFIRI. Even in the cetuximab monotherapy group, a partial response (PR) was observed in 2 patients, demonstrating a strong cytoreductive effect. Tumor markers also showed large decreases, with the percent decrease at 1 month being 31.7% and 60.8% in the monotherapy and combination therapy groups, respectively, while it was respectively 14.1% and 29.5% at 2 months. The mean progression-free survival (PFS) time and the time to treatment failure (TTF) were respectively 3.0 months and 4.5 months in the monotherapy group versus 7.3 months and 9.3 months in the combination therapy group. Acneiform rash and paronychia occurred in all 6 patients.

Topics: Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cetuximab; Colorectal Neoplasms; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Rectal Neoplasms; Sigmoid Neoplasms

We report two cases of venous thrombosis confirmed during the bevacizumab combination chemotherapy for colorectal cancer. Case 1 was a 59-year-old man. We performed an operation for cancer of the rectum. At 2 years after the operation, he received mFOLFOX6 + bevacizumab therapy for a recurrence in the pelvis and lungs metastasis. After the 14th courses, He had a right shoulder pain and contrast enhanced computed tomography revealed deep vein thrombosis to the right arms. Case 2 was a 65-year-old man. We performed an operation for cancer of the rectum. At 6 months after the operation, he received mFOLFOX6 + bevacizumab therapy for lung metastases. After the 6th courses, contrast enhanced computed tomography revealed deep venous and pulmonary thrombosis for both sides, pulmonary thrombosis.

Topics: Aged; Angiogenesis Inducing Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Pulmonary Embolism; Rectal Neoplasms; Venous Thrombosis

A 57-year-old man was diagnosed as having advanced rectal cancer that was suspected for a prostatic gland invasion. CPT-11 plus UFT/LV-based chemoradiotherapy (CRT) was administered. A total radiation dose was 50.4 Gy. After completion of CRT, rectal tumor has shrunken, but Virchow's lymph node metastasis was found on PET CT scan. Therefore, the main rectal tumor was resected first, and chemotherapy was then planned. After an abdominoperineal resection, mFOLFOX6 was started. We have stopped mFOLFOX6 after 9 courses because of grade 3 peripheral neuropathy. FOLFIRI was administered thereafter for 27 courses until the confirmation of the shrinkage of the Virchow's lymph node. With a request from the patient, the chemotherapy was stopped for 7 months. Virchow's lymph node has re-grown. We restarted chemotherapy with FOLFOX + bevacizumab regimen. Although the re-grown Virchow's lymph node was unresectable, a tumor in the rectum was resected for a control of local symptom. We, then, introduced a sequential systemic chemotherapy. After that, we could continue the treatment for 38 months without spoiling the QOL. The patient is alive and come to see us as an outpatient.

Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Combined Modality Therapy; Fluorouracil; Humans; Irinotecan; Leucovorin; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Organoplatinum Compounds; Rectal Neoplasms; Tegafur; Uracil

Neoadjuavnt chemotherapy for liver metastasis of colorectal cancer implies issues about timing for resection and management for adverse events due to chemotherapy.. A 50-year-old male patient with synchronous liver metastasis from rectal cancer had a surgery for primary lesion followed by neo-adjuvant chemotherapy for liver resection. Chemotherapy of bevacizumab + mFOLFOX6 achieved a partial response for liver metastasis. When we planned a liver resection, platelet count decreased to 1.4 × 10(4)/µL. The patient was diagnosed as idiopathic thrombocytopenic purpura (ITP) by several examinations but medical control including steroids failed. Partial splenic artery embolization could recover platelet count successfully. However, during the period of therapy for ITP, liver metastasis became unresectable. The patient is currently treated by FOLFIRI and with stable disease for three months.. NeoPyloriadjuvant chemotherapy for respectable liver metastasis should be considered carefully in terms of timing for resection and prompt management for adverse events.

Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Embolization, Therapeutic; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Purpura, Thrombocytopenic, Idiopathic; Rectal Neoplasms; Splenic Artery

A 42-year-old man with advanced rectal cancer underwent a low anterior resection with TME and pelvic lateral lymph-node and paraaortic lymph-node dissections. Pathological examination revealed as Type 2, 84 × 70 mm, tub 2 > por, A-SE, int, INF b, ly3, v1, pN3 (35/68), M1 (No. 216: 24/37), Stage IV (Cur B) by Japanese Classification of Colorectal Carcinoma. Three kinds of chemotherapy, 3 courses of irinotecan and bolus fluorouracil plus Leucovorin (IFL), 4 courses of irinotecan and S-1 (IRIS), and one-year of S-1 were administered sequentially. After 5 years from the operation, the patient survived and showed no sign of recurrence. Aggressive lymph-node dissection for rectal cancer patients with massive lymph-node metastasis followed by intensive chemotherapy may result in long-term survival.

Topics: Adult; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Aorta, Abdominal; Camptothecin; Combined Modality Therapy; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Fluorouracil; Humans; Irinotecan; Leucovorin; Lymph Node Excision; Lymphatic Metastasis; Male; Oxonic Acid; Pelvis; Rectal Neoplasms; Tegafur; Vitamin B Complex

We report a case of successfully treated lower rectal cancer with both inguinal lymph nodes by chemoradiotherapy. A 59-year-old man presented with anal pain. A colonoscopy revealed primary rectal cancer. The histological diagnosis was well to moderately differentiated adenocarcinoma. A computed tomography showed metastases to pararectal, both inguinal lymph nodes and right external iliac. After a ileostomy construction was done, he was treated with intensity modulated radiotherapy (a total 50.4 Gy) and chemotherapy with FOLFOX. The primary tumor had completely disappeared, and metastases to lymph nodes showed a remarkable shrinkage after the chemoradiotherapy. Nine months after radiation therapy, however, multiple lung and liver metastases were observed by a computed tomography, which were treated by systemic chemotherapy with FOLFOX and bevacizumab. The primary tumor and metastases to lymph nodes are still controlled well for 2 years after the initial chemoradiotherapy.

Topics: Adenocarcinoma; Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Combined Modality Therapy; Fluorouracil; Humans; Ileostomy; Inguinal Canal; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Organoplatinum Compounds; Radiotherapy, Intensity-Modulated; Rectal Neoplasms

A 54-year-old male had huge pre-sacral recurrent mass (54 × 41 mm) at the level of S1 sacral bone six months after he underwent a high anterior resection for advanced rectal cancer. He was considered inoperable although he had no distant metastasis. We planned a surgical resection for the recurrent tumor after the chemo-radiation therapy (radiation + CPT-11, UFT, Leucovorin). The tumor had a good response (33 × 29 mm) for CRT allowing a dissection area between sacral bone and posterior tumor margin. The surgical resection was performed. We dissected recurrent tumor and sacral bone below S2 and preserved S1 nerve roots under direct vision in order to prevent complications such as walking disorder and spinal fluid leakage. The operative time was 870 minutes and the blood loss was 3,600 g. There were no intraoperative complications. Macroscopically, surgical margin was well secured and a pathological examination of resected specimen revealed microfoci of cancer cells. The post operative hospital stay was 36 days. The patient is alive without any evidence of recurrence 72 months after surgery. He has no walking disability, and a good quality of life.

Topics: Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Combined Modality Therapy; Humans; Irinotecan; Length of Stay; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Quality of Life; Rectal Neoplasms; Sacrum; Tegafur; Uracil; Vitamin B Complex

A 72-year-old man was admitted with melena. Colonoscopy detected an advanced rectal cancer. CT scan revealed the prostate was invaded. We decided to start a systemic chemotherapy (mFOLFOX6). The chemotherapy (mFOLFOX6) was performed six times. After the treatment with chemotherapy, the tumor shrunk. Abdominoperineal resection of rectum was done, and a final pathological examination revealed a complete response of the main tumor.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Leucovorin; Male; Neoadjuvant Therapy; Organoplatinum Compounds; Rectal Neoplasms

We report here a case of rectal cancer with synchronous multiple liver metastases successfully treated with a combined chemotherapy of modified FOLFOX6 (mFOLFOX6) and bevacizumab. A 49-year-old man was admitted to our hospital due to constipation and anorexia. Abdominal ultrasonography and abdominal computed tomography (CT) scan revealed a rectal tumor (Rs) and abdominal abscess and 11 mm hepatic nodular lesion in S3 and 21 mm and 14 mm hepatic nodular lesions in S4. We diagnosed the patient had penetrated rectal cancer (Rs) and multiple liver metastases. We underwent a low anterior resection with D3 lymphadenectomy for the first time. After the operation, an 8 mm new liver metastasis in S6 appeared. We performed a combined therapy of mFOLFOX6 and bevacizumab 16 days after post operation. After the 8th course, there were a notable reduction in S3 and S4 liver metastases, and S6 liver metastasis was unidentifiable upon imaging. At this point, we underwent liver left lobectomy using the Liver Hanging Maneuver Method. After the second operation, there has been no recurrence and same chemotherapy is being continued.

Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Combined Modality Therapy; Fluorouracil; Hepatectomy; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Rectal Neoplasms

We report a CR case of advanced rectal cancer successfully treated with 39 courses of mFOLFOX6. The patient was a 29-year-old female with Stage IV rectal cancer. At first she was given IFL together with radiotherapy. It took effect for three months, and the therapeutic effect was PR, but interstitial pneumonia developed. Therefore, we shifted to mFOLFOX6, and she was treated with 39 courses. Grade 1 appeared several times for peripheral neuropathy, but recovered immediately. If we could control peripheral neuropathy with FOLFOX, it was thought that long-term survival could / be expected.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Neoplasm Staging; Organoplatinum Compounds; Proctoscopy; Rectal Neoplasms; Remission Induction; Tomography, X-Ray Computed

A 68-year-old man underwent laparoscopic low anterior resection for rectal carcinoma in December 2006. Nearly 19 mo after the operation, he developed recurrent rectal cancer with peritoneal metastasis. In September 2008, he subsequently underwent a laparotomy with a peritonectomy, omentectomy, splenectomy, and a Hartmann procedure. Hyperthermic intraperitoneal oxaliplatin 750 mg was administered. The patient was discharged with no postoperative complications and has been well with postoperative FOLFOX chemotherapy.

Topics: Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Fluorouracil; Humans; Laparoscopy; Leucovorin; Male; Neoplasm Metastasis; Neoplasm Recurrence, Local; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms; Rectal Neoplasms; Treatment Outcome

Oxaliplatin in combination with 5-fluorouracil (5-FU) and Leucovorin (FOLFOX) currently represents a valid approach for treating advanced colorectal cancer. In Japan, it is generally performed. Gastrointestinal, hematological and neurosensory toxicities are the most common. However, information concerning the pulmonary toxicity of this regimen is very limited. We report here two cases of interstitial lung disease occurring in association with the use of this combination chemotherapy. Reports of interstitial lung disease due to FOLFOX are infrequent, but could lead to severe complications. It is important to perform an X-ray examination regularly and detect symptoms early.

Topics: Aged; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Diseases, Interstitial; Male; Organoplatinum Compounds; Rectal Neoplasms; Tomography, X-Ray Computed

To date, the standard treatments for severe anticipatory nausea and vomiting is not well established. 5-HT3 antagonist is one of the effective drugs to reduce chemotherapy-induced nausea and vomiting, but had no effect on these symptoms for this patient. The patient could be successfully administered standard chemotherapy(FOLFOX or FOLFIRI, q2w)without adverse reactions by appropriate treatments in the form of increased doses of dexamethasone and normal dose administration of prochlorperazine. This report suggests a possibility that FOLFOX or FOLFIRI may be successfully treated by appropriate treatments for severe chemotherapy-induced vomiting colon cancer patients, and that this observation may lead to the improved prognosis of these patients.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Nausea; Neoplasm Staging; Organoplatinum Compounds; Rectal Neoplasms; Vomiting

Topics: Adenocarcinoma; Adrenal Gland Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Leucovorin; Middle Aged; Organoplatinum Compounds; Positron-Emission Tomography; Rectal Neoplasms; Tomography, X-Ray Computed

The 57-year-old man was underwent sigmoid colostomy due to unresectable rectal carcinoma. Then he was treated with chemotherapy of levofolinate/5-fluorouracil/oxaliplatin(FOLFOX). After completion of 12 courses of chemotherapy, MR revealed responses. The patient underwent a low anterior resection. Preoperative chemotherapy with FOLFOX appears a promising regimen for patients with unresectable rectal cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Leucovorin; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Organoplatinum Compounds; Proctoscopy; Rectal Neoplasms

A sixties-man had complained of melena. Colonoscopy revealed type 2 tumor at rectum. Computed tomography (CT)demonstrated lymph node metastasis in front of sacrum and two low density areas which were suspected metastases in the liver. The patient was diagnosed stageIV rectal cancer and resected primary focus and lymph node metastasis.[ Ra-RS, ant, type 2, moderately differentiated adenocarcinoma, ly1, v3, pSE, pN2, sH1(Grade C), sP0, pM1(No. 270)]without liver resection. It was due to high level of CEA and remote lymph node metastasis. The patient was treated with mFOLFOX6 and bevacizumab after the operation. The level of CEA decreased to normal level and CT revealed a partial response after 4 cycles of systemic chemotherapy. Liver resection was performed safely. Histological response was Grade 2 at liver metastases.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Carcinoembryonic Antigen; Fluorouracil; Humans; Immunotherapy; Leucovorin; Liver Neoplasms; Male; Organoplatinum Compounds; Rectal Neoplasms; Tomography, X-Ray Computed

A 78-year old man underwent low anterior resection for Stage IIIb rectal cancer(Ra). After surgery, he underwent the Roswell Park Memorial Institute(RPMI)regimen for 6 months followed by oral UFT for 8 months. Since liver metastasis(S6)recurred 2 years and 2 months after surgery, he underwent S6 subsegmentectomy. Four years and 4 months later, he developed multiple lymph node metastases(the Virchow, paraaortic, and intrapelvic lymph nodes), for which FOLFIRI therapy was started, but converted to the RPMI regimen because of strong gastrointestinal side effects. After 3 courses of this regimen, tumor markers returned to normal, and imaging studies showed that the metastases had disappeared. This was interpreted as a complete response(CR). The patient has maintained the complete response for 1 year and 4 months since the start of the RPMI regimen.

Topics: Aged; Antineoplastic Agents; Biomarkers, Tumor; Fluorouracil; Humans; Leucovorin; Lymphatic Metastasis; Male; Positron-Emission Tomography; Rectal Neoplasms; Remission Induction; Tomography, X-Ray Computed

A 54-year-old man was referred to our hospital because of a huge, unresectable rectal cancer occupying his entire pelvic space with a solitary liver metastasis. He had undergone a laparotomy for surgical resection, but ended up with a sigmoid colostomy due to possible invasion into the urinary bladder and pelvic wall. At the completion of seven cycles of FOLFOX regimen, radiographic examination revealed remarkable reduction of the primary rectal tumor and regional lymph nodes, and also a complete response (CR) of the liver metastasis. The tumor was extirpated without any macroscopic residues by a low anterior resection of the rectum, along with a partial resection of the urinary bladder and seminal vesicles. Since pathological and immunohistochemical examinations showed no viable cancer cells in any parts of the resected specimens, the lesion was regarded as a pathologically CR. Analysis for single-nucleotide polymorphisms in the genes involved in nucleotide excision repair, excision repair cross-complementing group 1 and xeroderma pigmentosum group D, showed a genotypic pattern sensitive to oxaliplatin. To our knowledge, this is a rare case of an initially unresectable primary rectal cancer, which was down-staged to a pathologically CR by FOLFOX chemotherapy instead of chemoradiotherapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; DNA-Binding Proteins; Drug Resistance, Neoplasm; Endonucleases; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Polymorphism, Single Nucleotide; Rectal Neoplasms; Remission Induction; Xeroderma Pigmentosum Group D Protein

A 75-year-old man was diagnosed with gastric cancer (UL post c0- II c (c T1N0) and M-less ctype II (cT2N0)) and rectal cancer (Rb ctype II (cT2N1) with multiple lung metastases (M1). The patient was treated with modified (m) FOLFOX6 regimen (oxaliplatin in combination with infusional 5-fluorouracil/Leucovorin). Chest and abdominal CT scan revealed that multiple lung metastases and abdominal lymph node metastases were obviously reduced in size. The primary lesion of the rectum almost disappeared on endoscopic examination. As for the lesions of the stomach, the UL post c0- II c lesion completely disappeared, and the M-less ctype II lesion was reduced remarkably. Thus, a significant reduction of the tumors was observed. This case suggests that mFOLFOX6 regimen can be an option for gastric cancer.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Leucovorin; Male; Neoplasms, Multiple Primary; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms; Stomach Neoplasms; Vitamin B Complex

5-Fluorouracil (5-FU) is a chemotherapeutic agent commonly used in a number of solid malignancies, including colorectal cancer. Herein, we report the first case of 5-FU-induced psychosis. Psychosis occurred after the first 2 cycles of 5-FU, oxaliplatin, leucovorin, plus bevacizumab and recurred upon rechallenge with further 5-FU and leucovorin.

Topics: Adenocarcinoma; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Female; Fluorouracil; Humans; Leucovorin; Magnetic Resonance Imaging; Neoplasm Recurrence, Local; Organoplatinum Compounds; Oxaliplatin; Prognosis; Psychotic Disorders; Rectal Neoplasms; Treatment Outcome

A postoperative rectum cancer patient with lung metastasis undergoing hemodialysis was treated with mFOLFOX6 therapy. The primary dose of oxaliplatin (L-OHP) ranged from 60 mg/m(2) to 85 mg/m(2), and adverse reactions and serum platinum concentration were monitored. The free platinum concentration (f-Pt), was eliminated efficiently using dialysis. The patient was tolerant of L-OHP doses of 60 mg/m(2) and 70 mg/m(2), but grade 2 neutropenia and grade 3 hemoglobin decrease developed with an L-OHP dose of 85 mg/m(2). The f-Pt after hemodialysis was higher than that before hemodialysis with a dose of 85 mg/m(2). But even with an 85 mg/m(2) dose, mFOLFOX6 therapy could be continued by extending the dosing interval. The monitoring of serum platinum concentrations, as well as therapeutic monitoring based on pharmacokinetics, contributes to safety management of cancer chemotherapy.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms; Renal Dialysis

Prognosis of stage II colorectal cancer varies. Whether or not to perform adjuvant chemotherapy on patients with stage II colorectal cancer is controversial. This study was to explore the prognostic factors for the patients with stage II colorectal cancer and evaluate the effect and the necessity of adjuvant chemotherapy.. Between January 2000 and January 2005, 443 patients with stage II colorectal cancer receiving radical surgery at Sun Yat-sen University Cancer Center were retrospectively analyzed. The overall survival rate and survival curve were analyzed using the Kaplan-Meier method and the log-rank test. The univariate and multivariate prognostic analyses were performed by the Cox regression model. Patients with or without chemotherapy (Xelox/Folfox regimen) with high-risk factors were analyzed respectively.. The median follow-up time was 59 months, and the 3-and 5-year survival rates were 88.4% and 82.5%, respectively. Univariate analysis showed that intestinal obstruction or perforation, diabetes mellitus, inadequate surgical margin, and the number of sampled nodes < 9 were poor prognostic factors. Patients with intestinal obstruction or perforation, the number of sampled nodes < 9 achieved higher 5-year survival (80% and 86%) undergoing adjuvant chemotherapy than those receiving surgery alone (67% and 64%).. The prognosis of colorectal cancer patients with intestinal obstruction or perforation, diabetes mellitus, inadequate surgical margin, and the number of sampled nodes < 9 are relatively poor. Adjuvant chemotherapy is recommended to patients with intestinal obstruction, perforation or sampled nodes < 9.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemotherapy, Adjuvant; Child; Colonic Neoplasms; Deoxycytidine; Female; Fluorouracil; Follow-Up Studies; Humans; Intestinal Obstruction; Intestinal Perforation; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaloacetates; Proportional Hazards Models; Rectal Neoplasms; Retrospective Studies; Survival Rate; Young Adult

Patients with locally advanced rectal cancer undergoing preoperative radiotherapy have disparity in pathological tumor regression. This study was to investigate clinicopathologic factors correlated with pathological complete response (pCR) following preoperative radiotherapy in rectal adenocarcinoma.. In total 132 patients with rectal adenocarcinoma received preoperative radiation from January 2002 to June 2008 at Sun Yat-sen University Cancer Center. Pathological tumor response after radiation was evaluated, and correlations of pCR to 12 clinicopathologic factors were analyzed using logistic regression method.. A total of 18 patients achieved pCR after preoperative radiation, with a pCR rate of 13.6%. Univariate analysis showed that pretreatment T stage with or without concomitant chemotherapy, pretreatment serum CEA level, and CA199 level were correlated with pCR after preoperative radiation in rectal adenocarcinoma. Multivariate analysis revealed that pretreatment serum CEA level and with or without concomitant chemotherapy were independent factors for pCR after radiotherapy in rectal adenocarcinoma.. Patients undergoing preoperative radiochemotherapy with a low pretreatment serum CEA level were more likely to achieve pCR.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; CA-19-9 Antigen; Carcinoembryonic Antigen; Female; Fluorouracil; Humans; Leucovorin; Logistic Models; Male; Middle Aged; Multivariate Analysis; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Preoperative Care; Rectal Neoplasms; Remission Induction

Neoadjuvant therapy (radiotherapy, RT or chemoradiotherapy, CRT) could change status of the invasion and lymph node metastasis of rectal cancer. The risk factors of lymph node metastasis in rectal cancers without neoadjuvant therapy have been well known, but those in rectal cancers treated with preoperative RT or CRT remain unclear. This study was to investigate the risk factors of lymph node metastasis in patients who underwent preoperative RT or CRT for rectal cancers.. Clinical data of 93 patients underwent preoperative RT or CRT followed by total mesorectal exesion (TME) for locally advanced rectal adenocarcinoma from August, 2003 to February, 2008 were reviewed. Twelve clinicopathologic factors and treatment-related factors were studied with univariate and multivariate analyses.. Univariate analysis showed that post-RT or post-CRT serum carcinoembryonic antigen (CEA) level, radiation dose, time interval from RT or CRT to TME, concurrent chemotherapy with oxaliplatin-containing regimens, and infiltration extent to bowel wall after RT or CRT (ypT stage) were significantly associated with lymph node status after RT or CRT (ypN stage). Multivariate analysis showed that concurrent chemotherapy with oxaliplatin-containing regimens (r=-0.481, P<0.01) and ypT stage (r=0.503, P<0.01) were independent risk factors of ypN stage.. Pathologic T stage is the most reliable predictor of lymph node stage in rectal cancer patients received preoperative RT or CRT. Oxaliplatin-containing regimens could significantly reduce the risks of lymph node metastases and potentially improve the prognosis.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; CA-19-9 Antigen; Carcinoembryonic Antigen; Female; Fluorouracil; Humans; Leucovorin; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Multivariate Analysis; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Preoperative Care; Radiation Dosage; Rectal Neoplasms; Rectum; Retrospective Studies; Risk Factors; Time Factors; Young Adult

An increase in carcinoembryonic antigen (CEA) and/or carbohydrate antigen 19-9 (CA19-9) levels is generally considered as tumor progression in patients with metastatic colorectal cancer (MCRC). However, a transient CEA surge has been observed in patients with MCRC responding to chemotherapy. This study was to investigate the clinical significance of transient CEA/CA19-9 surges in Chinese MCRC patients.. One hundred and twenty-one MCRC patients with histologically proven adenocarcinoma and baseline ECOG performance status of < or =2 were treated with oxaplatin and (or) irinotecan-based chemotherapy regimens. Serum CEA and CA 19-9 levels were measured before and after chemotherapy.. Of the 121 patients, 14 (11.6%) had transient CEA surges with median baseline CEA level of 45 microg/L (9.67-2208 microg/L) and median surge peak level of 80.1 microg/L (13.38-4044 microg/L). The transient CEA surge occurred at a median of 4 weeks (2-6 weeks), and lasted for a medium of 6.5 weeks (4-14 weeks). Of the 14 patients, 11 received oxaplatin-based chemotherapy; three received irinotecan-based chemotherapy. All the 14 patients showed clinical benefit from chemotherapy, among which seven achieved partial response and seven had stable disease. In the meantime, five patients (3.8%) had transient CA19-9 surges. However, no significant correlation was found between an increase in the CA19-9 level and clinical benefits.. Transient CEA surges can be observed in Chinese MCRC patients receiving oxaplatin or irinotecan-based chemotherapy, which does not indicate tumor progression, but good therapeutic efficacy. A transient elevation of CA19-9 is not correlated to short-term clinical benefits.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; CA-19-9 Antigen; Camptothecin; Capecitabine; Carcinoembryonic Antigen; Child; Colonic Neoplasms; Deoxycytidine; Disease Progression; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Oxaloacetates; Rectal Neoplasms; Remission Induction; Young Adult

We report a case of a 71-year-old male with rectal cancer accompanied by liver metastases. Abdominal CT scan revealed a hepatic tumor (S2, 3) about 4 cm in diameter. We performed a Mile's operation and planned to resect the liver metastases after chemotherapy of modified FOLFOX6(mFOLFOX6)regimen: l-leucovorin (200 mg/m2) and oxaliplatin (85 mg/m/2) were given as a 2-hour infusion followed by bolus injection of 5-FU 400 mg/m2 and a 46-hour infusion 5-FU 2,400 mg/m2 every 2 weeks. An abdominal CT scan 6 months later demonstrated regression of the liver metastases. Hepatectomy was performed after chemotherapy, and no viable tumor cells were seen.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Fluorouracil; Hepatectomy; Humans; Leucovorin; Liver Neoplasms; Male; Organoplatinum Compounds; Rectal Neoplasms

For rectal cancer in UICC stage II or III, a neoadjuvant chemoradiotherapy or short-course radiotherapy is established to reduce the incidence of local relapses. It has been documented that the neoadjuvant therapy is superior to the adjuvant therapy. In spite of the formulation of therapeutic principles in guidelines, they are not consistently applied. The actual rate of application and the reasons for a change from the recommended treatment strategy have been investigated.. The data of the tumour centre West Mecklenburg were analysed. Data concerning the type and stage of rectal cancer, multimodal treatment (surgery with or without neoadjuvant therapy or adjuvant therapy) and treatment according to the level of medical care of hospitals were recorded from 2000 to 2008. In addition, in our clinic prospectively collected data of patients with rectal cancer (September 2006 until December 2008) were used to find out the reasons for the denial of neoadjuvant therapy.. During the observation period we detected 348 patients with rectal cancer in UICC stage II or III in the area of the tumour centre West Mecklenburg. 16 % of these patients were treated pre-operatively. An increase in the preoperative multimodal treatment from 3 % to 39 % was observed. Hospitals with higher provisions of medical care applied the multimodal treatment 4-fold more frequently during this period of time. 55 patients of our own clinic were found to be of UICC stage II or III. 6 patients were emergency cases. The carcinoma was found in the lower or middle third of the rectum in 38 of our patients. The endosonographical examination could not adequately show the tumour or was falsely negative in 16 of these patients. A neoadjuvant treatment was started for 58 % of the patients. Overall, 76 of patients with rectal carcinoma were treated adjuvant or neoadjuvant, 62 of them with a complete treatment scheme.. The application of neoadjuvant treatment for rectal carcinoma in UICC stage II or III in West Mecklenburg was unexpectedly low during the observation period. However, an increase in treatment frequency was detected. During the same period of time the number of patients treated in hospitals of basic and standard medical care decreased by half. This is the reason for the regional increase of neoadjuvant treatment. 47 % of the patients of our clinic received neoadjuvant chemoradiotherapy or a short-course radiotherapy. Including the adjuvant treatment, 76 % of all patients were treated multimodally. An increase in neoadjuvant treatment can only be achieved by shifting patients to centres with an appropriate diagnostic facility and a regular tumour board for rectal cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cancer Care Facilities; Chemotherapy, Adjuvant; Combined Modality Therapy; Fluorouracil; Germany; Guideline Adherence; Humans; Leucovorin; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Radiotherapy, Adjuvant; Rectal Neoplasms; Referral and Consultation; Utilization Review

Despite of its rich vascularization and extensive circulatory communication with neighboring organs, penile metastases are rare. Even more infrequent is a penile metastasis of rectum tumors. Since the first report of rectal carcinoma with metastasis to the penis (Ehbert 1870), approximately 50 cases have been reported, most of them from the USA, the remaining from Western Europe, the Middle East and Japan. The first Hungarian case is reported now of penile metastasis of a rectal carcinoma. The case of a 65-year-old man is presented: isolated penile metastasis discovered 4.5 years after the primary rectal cancer resection. IHC tissue diagnosis and detailed clinical investigations confirmed metastatic rectal adenocarcinoma. As our patient refused penectomy and KRAS mutation was proven, FOLFIRI chemotherapy was initiated without cetuximab. This was followed by chemoradiotherapy that resulted only in transient regression. Currently the patient receives the FOLFOX regimen. At present the patient is in good performance status,without pain. The size and the number of penile metastases have not shown significant changes. According to the literature the average survival of patients with penile metastases treated with radiochemotherapy is 8 months. New chemotherapeutic modalities may improve the survival.

Topics: Adenocarcinoma; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cetuximab; Chemotherapy, Adjuvant; Diagnosis, Differential; Fluorouracil; Humans; Leucovorin; Male; Neoplasm Recurrence, Local; Neoplasms, Second Primary; Organoplatinum Compounds; Palliative Care; Penile Neoplasms; Radiotherapy, Adjuvant; Rectal Neoplasms; Treatment Outcome

The case was a 69-year-old man with liver metastasis who had relapsed after the resection of rectal cancer. We treated the patient with FOLFIRI+bevacizumab(BV)after the failure of S-1+CPT-11, radiation, UFT/LV, FOLFOX and FOLFIRI regimen. The tumor marker level and accumulation of FDG-PET were rapidly decreased after initiating FOLFIRI+BV. There was no serious adverse event, and a remarkable improvement of QOL was observed. This case suggests that the BV combination regimen is useful even after the failure of FOLFOX and FOLFIRI regimen.

Topics: Adenocarcinoma; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Organoplatinum Compounds; Oxaliplatin; Positron-Emission Tomography; Quality of Life; Rectal Neoplasms; Recurrence; Salvage Therapy

To suppress local recurrence and preserve sphincter function, we performed preoperative chemoradiotherapy( CRT) of rectal cancer. Sixteen patients with lower advanced rectal cancer received tegafur/uracil/calcium folinate+RT followed by curative resection with lateral lymph node dissection 2-8 weeks later. The male/female ratio was found to be 11:5 (41-75 years old) and the CRT was feasible for all patients. There were 11-PR and 5-SD according to RECIST criteria, and lower isotope accumulation was observed for all primary tumors in FDG-PET study. After CRT, all patients received R0 curative resection (11 APR, 2 LAR, 1 Hartmann and 1 ISR). On pathological study, 3 patients showed complete response. Surgical complications including pelvic infection, delayed a wound healing and deep venous thrombosis, etc. In conclusion, preoperative CRT of advanced rectal cancer could potentially be useful for local control and sphincter saving, however, it is necessary to manage specific surgical complications due to radiation.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Rectal Neoplasms; Tegafur; Uracil

We describe here two cases of locally advanced rectal cancer treated with neoadjuvant chemotherapy prior to surgery. The first patient was a 54-year-old man whose chief complaint was bloody stool. A detailed examination revealed a rectal cancer with direct invasion of the primary rectal carcinoma into the prostate. Four courses of FOLFOX4 were administered as neoadjuvant chemotherapy. Because the invasion to the prostate was difficult to determine by subsequent CT evaluation, we performed a radical resection. The pathological examination revealed that all surgical margins were negative for malignancy and no metastasis to lymph nodes was found, therefore a surgical evaluation of curability was classified as A. The second patient was a 49-year-old woman whose chief complaint was irregular menstruation. A detailed examination revealed a rectal cancer with metastasis to an ovary and paraaortic lymph node. One course of FOLFOX4 and six courses of mFOLFOX6 (combined with bevacizumab in the first five courses) were administered as neoadjuvant chemotherapy. Subsequent examinations revealed significantly reduced primary tumor and the size of metastatic lesion. Given that metastasis to the paraaortic lymph node was difficult to determine, we performed a radical resection. The pathological examination revealed that all surgical margins were negative for malignancy, and the postoperative FDG-PET evaluation did not find FDG accumulation to paraaortic lymph node. We determined that there was no residual cancer and evaluated the surgery as curability B. We conclude that neoadjuvant chemotherapy against locally advanced rectal cancer may improve the curability of the surgery and save the surrounding organs.

Topics: Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Rectal Neoplasms

A 78-year-old man was admitted to our institute with the symptom of melena. The patient was diagnosed as having advanced rectal cancer (T4N2M1) with multiple bone metastases. Chemoradiation therapy was chosen for the local control because our proposal of colostomy was rejected. Concurrent chemoradiation therapy [46 Gy/23 Fr+tegafur/uraci (l UFT 400 mg/m2)/calcium folinate (Leucovorin: LV 75 mg/body)] resulted in a good partial response and the patient became asymptomatic. UFT/LV were administrated and most of the bone metastases were diminished. After 3 years of disease remission with good quality of life, local tumor recurred with the symptoms of melena and bowel obstruction. Colostomy and additional radiotherapy were performed for the palliation. He died after 4 years from the initial treatment. In advanced rectal cancer with distant metastases, chemoradiation therapy for local control plus systemic chemotherapy could be an alternative to improve quality of life.

Topics: Aged; Bone Neoplasms; Combined Modality Therapy; Humans; Leucovorin; Male; Rectal Neoplasms

We report a case of multiple liver metastases of rectsigmoid colon cancer treated with systemic chemotherapy and hepatectomy. A 40s woman had undergone anterior resection of rectum for rectsigmoid colon cancer with multiple liver metastases. Then FOLFOX4 regimen was performed fifteen times, and FOLFIRI regimen was performed eleven times. After chemotherapy was enforced, an abdominal CT revealed that liver metastases were reduced in size (effect judgment of partial response). Hepatic resection of the right lobe and partial of S2 segment were performed. Pathological findings of the resected liver revealed no residual cancer cells, indicating that the histological effect of chemotherapy was complete response (CR).

Topics: Adult; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Organoplatinum Compounds; Rectal Neoplasms; Sigmoid Neoplasms

A man in his fifties with rectal cancer underwent low anterior resection in another Hospital in January 2006. He was finally diagnosed with Stage III a (pA, pN1, H0, P0). The patient who had postoperative complication such as ruptured suture left the hospital in May 2006, when he was detected with multiple liver metastases and was referred to our hospital for systemic chemotherapy. Systemic chemotherapy with mFOLFOX6 was performed from May 2006. Grade 3 diarrhea and grade 2 peripheral neuropathy, nausea and vomiting were observed. After 6 courses of mFOLFOX6, MRI revealed metastasis had been disappeared and levels of CEA and CA19-9 were decreased below normal. The treatment has been discontinued. Recurrence was not observed for 30 months.

Topics: Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Rectal Neoplasms; Treatment Outcome

We report a case of rectal cancer with unresectable multiple liver metastases, which was worried about the transition from liver dysfunction to liver failure. The male patient in his 70s was diagnosed as advanced rectal cancer with severe liver dysfunction because of multiple liver metastases. Hepatic arterial infusion (HAI) chemotherapy, which was effective to reduce the size of metastatic liver tumors, was initially started. During HAI chemotherapy, sigmoid colostomy was performed. He recovered from liver dysfunction after he had been treated with 13th cycle HAI chemotherapy. He was treated with the modified FOLFOX6 regimen following a resection of rectal cancer. Although the standard therapy for colorectal cancer with unresectable liver metastases is firstly systemic chemotherapy such as FOLFOX or FOLFIRI, it might be better to control the liver metastases by HAI chemotherapy when a liver function is severely damaged by extensive liver tumors.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Hepatic Artery; Humans; Infusions, Intra-Arterial; Leucovorin; Liver Diseases; Liver Neoplasms; Male; Organoplatinum Compounds; Rectal Neoplasms

A 63-year-old female diagnosed as rectal cancer underwent low anterior resection and received adjuvant chemotherapy (folinate/tegafur/uracil therapy). After 6 months, lymph node metastasis was confirmed by an elevation of the tumor marker (CEA) and a FDG-PET image. After administration of 37 courses of mFOLFOX6 therapy, surgical excision was performed to the lymph node recurrence, because it was difficult to continue mFOLFOX6 therapy with grade 3 neuropathy. After 8 months from the last operation, no lymph node metastasis was appeared in the para-aortic area.

Topics: Antineoplastic Combined Chemotherapy Protocols; Aorta, Abdominal; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Lymphatic Metastasis; Middle Aged; Organoplatinum Compounds; Rectal Neoplasms

This retrospective study was performed to clarify problems associated with surgery for local recurrence of rectal cancer in recent years when new anticancer drugs have come out to be available. We compared the background characteristics and treatment outcomes of patients who underwent resective surgery (resection group, n=9) and those who received chemotherapy comprised of new aniticancer drugs (chemotherapy group, n=5) for intrapelvic recurrence of rectal cancer between 1997 and 2008. In the resection group, the types of surgery included were abdomino-perineal resection in 1, posterior exenteration in 4, total pelvic exenteration in 4 and 5 who underwent sacrectomy. In the chemotherapy group, chemotherapy was continued to second-line treatment in 4 patients and third-line in 1. Oxaliplatin was given to 3 patients, irinotecan to 3, and Leucovorin to 5. The two groups did not significantly differ regarding various background factors including age, sex, stage at resection of the primary lesion, and the interval between resection of the primary lesion and detection of recurrence. The overall survival period after the start of treatment for recurrence did not significantly differ between the two groups (p=0.73). Patient's selection seems to have become a more important factor for resective surgery for intrapelvic recurrence of rectal cancer in recent years when the efficacy of new anticancer drugs is expected.

Topics: Aged; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Camptothecin; Female; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Organoplatinum Compounds; Oxaliplatin; Patient Selection; Pelvis; Rectal Neoplasms; Retrospective Studies; Treatment Outcome

The platinum agent oxaliplatin could be useful in treatment of cancer in pregnant women, but it is fetotoxic in rats and its effect on the human fetus is unknown.. Oxaliplatin was administered to a 25-year-old pregnant woman with metastatic rectal cancer from 20 to 30 weeks gestational age as part of the mFOLFOX-6 regimen.. The patient gave birth to a healthy girl at 33 weeks gestational age. At follow-up, the 3-year-old child had achieved all appropriate growth and developmental milestones.. Oxaliplatin is a component of several modern chemotherapy regimens. This report demonstrates the administration of oxaliplatin in the second and third trimesters of pregnancy without apparent fetal harm.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Disease-Free Survival; Female; Fetal Development; Fluorouracil; Humans; Infant, Newborn; Leucovorin; Liver Neoplasms; Lymphatic Metastasis; Organoplatinum Compounds; Oxaliplatin; Pregnancy; Pregnancy Outcome; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Rectal Neoplasms

Pneumatosis cystoides intestinalis (PCI) is a relatively rare condition characterized by intraluminal gas in the gastrointestinal tract. Several chemotherapeutic agents have been reported to be associated with PCI, although fluorouracil-related PCI is extremely rare. We report a case of a 76-year old man who received adjuvant chemotherapy for rectal cancer with fluorouracil (FU) and leucovorin (LV). After 1 cycle of the treatment, he presented with diarrhea and abdominal pain. Abdominal radiogram revealed the presence of free air under the diaphragm and intramural gas in the intestine. Laparotomy was performed, showing a suspected diagnosis of perforation in the gastrointestinal tract. Intraoperative findings revealed penumatosis of the intestine without evidence of perforation. He was treated supportively and his symptoms improved. In conclusion, we should consider the possibility of PCI occurring in patients with malignancies during chemotherapy treatment.

Topics: Aged; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colonoscopy; Combined Modality Therapy; Fluorouracil; Gastrostomy; Humans; Leucovorin; Male; Oxygen; Parenteral Nutrition; Pneumatosis Cystoides Intestinalis; Rectal Neoplasms; Tomography, X-Ray Computed; Treatment Outcome

Granulocyte-colony stimulating factor (G-CSF)-producing cancer has been reported to occur in various organs, especially the lung. However, G-CSF-producing colorectal cancer (CRC) has never been reported in the English literature.. A 57-year-old man was admitted for the surgical removal of a rectal cancer. Some hepatic tumors in the liver were revealed concurrently, and their appearance suggested multiple liver metastases. Low anterior resection was performed. with the help of histopathological examination and immunohistochemical studies, we diagnosed this case to be an undifferentiated carcinoma of the rectum. After the operation, the white blood cell (WBC) count increased gradually to 81,000 cells/microL. Modified-FOLFOX6 therapy was initiated to treat the liver metastases, but there was no effect, and peritoneal dissemination had also occurred. The serum level of G-CSF was elevated to 840 pg/mL (normal range, <18.1 pg/mL). Furthermore, immunohistochemistry with a specific monoclonal antibody against G-CSF was positive; therefore, we diagnosed this tumor as a G-CSF-producing cancer. The patient died from rapid growth of the liver metastases and peritoneal dissemination 2 months after surgery.. This is the first case of G-CSF-producing rectal cancer, and its prognosis was very poor.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Colectomy; Fatal Outcome; Fluorouracil; Granulocyte Colony-Stimulating Factor; Humans; Immunohistochemistry; Leucovorin; Liver Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Peritoneal Neoplasms; Prognosis; Rectal Neoplasms

The aim of our study was to determine the accuracy of endorectal ultrasonography (ERUS) in staging locally advanced rectal cancer after preoperative neoadjuvant chemoradiation and to point out the most common reasons for false interpretation.. Forty-four patients with locally advanced rectal cancer received neoadjuvant chemoradiation followed by radical surgery. Restaging was done 1-2 weeks before surgery and the results of ERUS staging were compared with histopathology findings of the resected specimen.. The accuracy of ERUS for T stage after chemoradiation was 75% (33/44). Overstaging occurred in 18% (8/44) of patients, and 7% (3/44) were understaged. The majority of overstaging occurred in patients with ERUS T3 tumors, eventually found to have pathological pT0-pT2 staging. Five patients (11.4%) had complete histology regression and only one of these patients was staged correctly while others were overstaged. In the detection of perirectal lymph node metastases, ERUS was accurate in 68% of patients (30/44). Twenty percent (9/44) of patients were overstaged and 11% were (5/44) understaged.. ERUS provides a good accuracy rate for staging rectal cancer after neoadjuvant chemoradiation. However, it is insufficient in detection of complete pathological response.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Endosonography; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Preoperative Care; Radiotherapy Dosage; Rectal Neoplasms

A 61-year-old man underwent amputation of the rectum for advanced lower rectal cancer in April 2005. UFT-E granules were administered orally daily at 400 mg/body/day following surgery. He developed perineal pain and perineal discharges following an increase the CEA level in April 2006. PET revealed a tumor in the perineum and multiple lung metastases. Chemotherapy with mFOLFOX 6 for 8 courses and FOLFIRI 2 for 4 courses were administered since July in 2006. Although CT revealed a the reduction in multiple lung metastases, CEA was increased to over a maximum 109, high fever continued and the pinealtumor was enlarged in December 2006. The patient underwent resection of the perinealmass, but he developed perinealsevere pain and perinealdischarge. So radiotherapy of the pelvic region was given at a total dose of 40 Gy(given 2 Gy each fragment)followed by administration of FOLFIRI 2 for 12 courses. After chemoradiotherapy, the CEA level was remarkably decreased. PET could not detect any mass in lung fields and revealed a little accumulation in the pelvic region. Chemotherapy with FOLFIRI 2 is administered monthly now, and the CEA level has been within the normal range since July of 2007. The pineal pain and pineal discharge disappeared, so the quality of life has improved dramatically.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoembryonic Antigen; Cisplatin; Combined Modality Therapy; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Peritoneal Neoplasms; Positron-Emission Tomography; Rectal Neoplasms; Recurrence; Tomography, X-Ray Computed

Chemotherapy for advanced or recurrent colorectal cancer is standardized as oxaliplatin/5-FU/LV therapy (FOLFOX)and irinotecan/5-FU/LV therapy(FOLFIRI). It is difficult to introduce cancer chemotherapy to hemodialysis patients, and limited chemotherapeutics are available. The case was a 57-year-old man who was undergoing continuous hemodialysis when rectal cancer was found with multiple hepatic metastases. After rectum elevation and anterior resection, we treated him with 5-FU/LV therapy. After three courses the number of hepatic metastatic foci decreased, and the ascites disappeared. Levels of carcinoembryonic antigen(CEA)decreased from 837 ng/mL to 29 ng/mL; carbohydrate antigen 19-9(CA19-9)decreased from 79.6 U/mL to 14.2 U/mL, and cancer-related antigen 72-4 (CA72-4)was reduced from 33.3 U/mL to 7.4 U/mL. Partial remission was achieved following the chemotherapy. We used 5-FU/LV therapy according to the Roswell Park Memorial Institute method. Our patient was able to undergo treatment safely without serious adverse drug response, except that he exhibited diarrhea and hand-foot syndrome of grade 2.

Topics: Biomarkers, Tumor; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Rectal Neoplasms; Renal Dialysis; Tomography, X-Ray Computed

Carcinoma of the large intestine is a common and relatively well known neoplastic malignancy of the digestive tract. In a very few cases its spread seems unpredictable and can cause a distant metastasis to head and neck region.. A 58 years old patient was admitted to the ENT Department because of an exulcerated tumour mass of the left mental and buccal region. 9 months earlier he underwent anterior resection of rectum due to carcinoma. Histopatological examination of specimen from the facial skin lesion revealed adenocarcinoma cells. Radiological findings suggested isolated character of lesion. The patient was treated by surgery and chemotherapy. Wide excision of tumour mass with partial mandibulectomy was performed and the tissue defect reconstructed with a pectoralis major musculocutaneous flap. A postoperative chemiotherapy with FA and 5-FU followed the surgical procedure. Regardless of the first promising results of the oncological treatment the patient died eight months later.. We present this case report as an example of an unusual and rare secondary malignancy of head and neck, emphasizing the interdisciplinary character of oncological treatment and the role of oncological vigilance on every step of diagnosis.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Facial Neoplasms; Fatal Outcome; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Radiotherapy, Adjuvant; Rectal Neoplasms; Skin Neoplasms

Oxaliplatin is a therapeutic platinum compound used for the treatment of colorectal cancer; however, it might induce hypersensitivity reactions, a critical situation that requires discontinuation of chemotherapies that contain oxaliplatin. Independent attempts of oxaliplatin desensitization have been reported, with mostly successful results. This letter reports a 53-year-old Japanese woman (weight, 70 kg) with chemorefractory metastatic rectal cancer who had undergone surgical intervention twice and received 3 treatment regimens. The patient developed grade 3 hypersensitivities to oxaliplatin during cumulative cycles of the FOLFOX (5-fluorouracil/leucovorin/oxaliplatin)-4 regimen. After the subsequent regimen failed, she was desensitized using a protocol of an 8-hour series of diluted-oxaliplatin infusions. Because, according to previously published desensitization reports, hypersensitivity reactions might recur during the final bag infusion of oxaliplatin despite intensive premedication, prophylactic antiemesis, corticosteroids, and antihistamines were administered twice (ie, before and during the oxaliplatin infusion). Allergic reactions were successfully and efficiently prevented with the 2 stages of intensive premedication in this patient who was able to receive oxaliplatin and had stabilized lung metastases. She was able to undergo desensitization for 5 cycles until acute development of obstructive pneumonia. In this report of a previously sensitized patient, a type I hypersensitivity reaction was successfully circumvented with 2-staged premedication for oxaliplatin desensitization. The optimum desensitization protocol for oxaliplatin administration in terms of efficacy and tolerability still needs to be defined.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Desensitization, Immunologic; Drug Hypersensitivity; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Premedication; Rectal Neoplasms

We report a 59-year-old woman with rectal cancer who underwent low anterior resection in March 2007. After curative operation at Stage IIIb(pT3N2M0), multiple liver metastasis was diagnosed in May 2007. Chemotherapy with FOLFOX4+bevacizumab was performed from June to August in 2007, and liver resection(left lobectomy and partial resection)was performed in September 2007. Bevacizumab was newly available from June 2007 in Japan, and liver resection after bevacizumab administration was safely performed.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Biomarkers, Tumor; Female; Fluorouracil; Hepatectomy; Humans; Immunotherapy; Leucovorin; Liver Neoplasms; Middle Aged; Organoplatinum Compounds; Rectal Neoplasms; Tomography, X-Ray Computed

The patient was a 57-year-old man. The chief complaints were bleeding upon defecation and decreased body weight. He came to our department in May 2006 because the bleeding had been observed since summer 2005 and he had lost 7 kg in one year. A tumor was palpable on the rectum, approximately 5 cm proximal to the anal verge. Abdominal CT revealed a large tumor within the pelvis and enlarged paraaortic lymph nodes. CEA was 14.0 ng/mL. The patient underwent surgery in June 2006, but the tumor was firmly fixed anterior to the sacrum. We judged it unresectable and performed double-barrel descending colostomy. FOLFOX4 chemotherapy commenced following the surgery, and the tumor marker level normalized following three cycles. Abdominal CT following five cycles showed that the size of the tumor had reduced significantly. Later, the patient developed grade 2 nausea and decreased appetite as adverse events, and the chemotherapy was discontinued at his request. We considered resection possible and performed rectal resection in November 2006. The patient underwent radiotherapy following surgery and is currently receiving S-1. FOLFOX4 may be an effective preoperative chemotherapy for unresectable primary rectal cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoembryonic Antigen; Colonoscopy; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Rectal Neoplasms; Tomography, X-Ray Computed

We report a case of diffusely infiltrating rectal cancer with pulmonary lymphangitis carcinomatosa that responded to mFOLFOX6 chemotherapy and enabled survival for 19 months. A 68-year-old man was admitted to our hospital for a dry cough and dyspnea. Chest X-ray and CT examination revealed prominent pulmonary markings and abnormal infiltrating shadows. Interstitial pneumonia was suspected, and we started treatment with steroid medication, but this had no effect. A colonoscopy and barium enema revealed diffusely infiltrating rectal cancer. Abdominal CT and PET showed lymphangitis carcinomatosa of the lung, paraaortic lymph node swelling, and left hydronephrosis due to rectal cancer. The patient was diagnosed with stage IV rectal cancer. Thus, a curative operation was deemed impossible. Because of subileus, we performed a decompression loop colostomy in the transverse colon, and started treatment with mFOLFOX6 chemotherapy as salvage in spite of the patient's poor respiratory condition. Though the patient's tumor markers were very high (CEA 107 ng/mL, CA19-9 7,940 U/mL) prior to chemotherapy, they decreased dramatically (CEA 49.7 ng/mL, CA19-9 772 U/mL), and subjective symptoms (dry cough and dyspnea) also improved after 2 courses. After 3 courses of treatment the patient was discharged. After 7 courses, pulmonary markings and abnormal infiltrating shadows had disappeared on chest X-ray and CT. This condition was maintained for 19 months by ambulant chemotherapy without sacrificing high quality of life. Thus, mFOLFOX6 chemotherapy could be an effective salvage regimen in cases of diffusely infiltrating rectal cancer with pulmonary lymphangitis carcinomatosa.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoembryonic Antigen; Fluorouracil; Humans; Leucovorin; Lung Diseases, Interstitial; Lymphangitis; Male; Organoplatinum Compounds; Rectal Neoplasms; Salvage Therapy; Tomography, X-Ray Computed

The patient was a 62-year-old male who underwent a high anterior resection for rectal cancer with multiple liver metastases in June 2004. After the operation, 66 courses of weekly hepatic arterial infusion(HAI)therapy of 5-FU/Leucovorin( LV)were performed. Thereafter 14 courses of FOLFOX 4, 5 courses of FOLFIRI and 5 courses of FOLFOX 4 therapy were also sequentially performed. As a result of the CT examination, which revealed a new metastatic lesion in the liver and lung metastases, combination chemotherapy consisting of UFT and HAI of low-dose CPT-11 was administered in July 2007. After 1 cycle of this therapy, metastatic liver and lung tumors showed a reduction rate of 8.5% and 27.0%, respectively, without any adverse events. The elevated serum CEA (2,055 ng/mL)and CA19-9 (924 U/mL) levels decreased to 623 ng/mL and 332U /mL, respectively, after 1 cycle of the treatment. The combination of oral UFT and HAI of CPT-11 may therefore be a useful treatment for patients after FOLFOX and FOLFIRI therapy.

Topics: Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Camptothecin; Fluorouracil; Humans; Infusions, Intra-Arterial; Irinotecan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Rectal Neoplasms; Tegafur; Tomography, X-Ray Computed; Uracil

A 75-year-old patient with colorectal cancer was treated by FOLFOX4 therapy. When the total dose of 5-fluorouracil reached 21,200 mg and the total dose of oxaliplatin reached 880 mg after about 100 days of treatment, epiphora developed. Because the pharmacist discovered it soon, he could consult with an ophthalmologist, and the man was diagnosed with subconjunctival hemorrhage. Thereafter, the symptom improved with ofloxacin eye drops. Attention must be paid to the visual side effect in case an anticancer agent is used and when aggressive involvement of the pharmacist in medical team treatment is expected.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Lacrimal Apparatus Diseases; Leucovorin; Liver Neoplasms; Male; Organoplatinum Compounds; Rectal Neoplasms

In the recent improvement in chemotherapy for advanced rectal cancer, a treatment for rectal cancer involving the surrounding organs has been well thought out. In this report, we described a case of advanced rectal cancer invaded into the surrounding organs was resected successfully after preoperative chemotherapy with mFOLFOX6. The case was a 74-year-old man with advanced rectal cancer (type 3). A close examination of the patient revealed a bowel movement disturbance. Bowel obstruction was treated with transverse colostomy. Then chemotherapy (mFOLFOX6) was performed six times. It was judged at first to be a huge tumor of 15 cm in diameter, which was unresectable due to invasion into the urinary bladder and sacrum. However, after mFOLFOX6 was enforced, the tumor was shrunk to about 5 cm in diameter (effect judgment PR). Then the tumor was successfully resected. A pathologic histology inspection of the tumor, judged to be Grade 2 prior to resection, revealed a differentiation type glandular carcinoma and a highly lymphocytic infiltration. These results suggested that an appropriate preoperative chemotherapy was useful for huge rectal cancers involving the surrounding organs such as urinary bladder and sacrum.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Leucovorin; Male; Neoadjuvant Therapy; Neoplasm Invasiveness; Neoplasm Staging; Organoplatinum Compounds; Rectal Neoplasms; Tomography, X-Ray Computed

Chemotherapy is potentially hazardous for patients with liver dysfunction. Although FOLFOX regimen is one of the standard chemotherapies for nonresectable liver metastases of colorectal cancer, the safety of this regimen has not been established yet in patients with obstructive jaundice associated with multiple liver metastases. We report a case of nonresectable liver metastases of rectal cancer treated by modified FOLFOX6 regimen after percutaneous transhepatic biliary drainage for obstructive jaundice, which was caused by hepatic lymph-node metastasis. Five days after giving a birth, a 32-year-old woman underwent Hartmann's procedure for perforation of rectal cancer associated with multiple liver metastases. She was admitted again to receive chemotherapy 35 days after surgery, but the level of total bilirubin was elevated (3.9 mg/dL). Since the total bilirubin level was not rapidly decreased after PTBD, the modified FOLFOX6 regimen was started with a 70% dose. After an introduction of mFOLFOX6 treatment, a biliary-stenting was successfully performed, and the mFOLFOX6 continued with a full dose starting from the 5th cycle. Although the therapeutic efficacy after an additional 8-cycle was classified as stable disease (SD), she did not show any sign of adverse effects except for grade 1 neurotoxicity.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Female; Fluorouracil; Humans; Jaundice, Obstructive; Leucovorin; Liver Neoplasms; Lymphatic Metastasis; Organoplatinum Compounds; Rectal Neoplasms; Stents; Tomography, X-Ray Computed

We report a case of complete remission of relapsed rectal cancer liver metastasis after systemic chemotherapy successfully treated by radiofrequency ablation (RFA). A 60-year-old man was diagnosed as having rectal cancer with colonoscopy and as solitary liver metastasis with enhanced CT. After primary tumor was resected, modified FOLFOX6 chemotherapy was performed. A complete response (CR) was observed after the eighth course, and the chemotherapy was finished at the twelfth course. Recurrence of liver metastasis was showed after the chemotherapy for six months, so RFA was performed without any complications. He is living without relapsing for eight months. We basically performed first was systemic chemotherapy to liver metastasis of colorectal cancer, and performed a local treatment including resection, if necessary. We suppose that RFA after systemic chemotherapy is one of the useful treatment strategies for liver metastasis of colorectal cancer, because RFA is less invasive than resection and a discontinuation of the drug is not required for RFA.

Topics: Antineoplastic Combined Chemotherapy Protocols; Catheter Ablation; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Radiography; Rectal Neoplasms; Remission Induction

A 64-year-old man was admitted to general practitioner because of dyschezia. He was diagnosed with lower rectal cancer by colonoscopy and referred to our hospital for therapy. At first, in spite of multiple liver metastases, we tried a resection of primary lesion in order to control of breeding, dyschezia and pain. However, we had to give up the resection, so we made sigmoid colostomy only. One month after the operation, a combination chemo-radiotherapy using S-1 was performed for controlling of local symptom. S-1 (120 mg/day) was administered on days 1-14, and 21-35. Radiation (2 Gy) was administered on days 1-5, 7-12, 14-19, 21-26, 28-33, and 35-40, a total of 60 Gy. One month after this therapy, the tumor was remarkably reduced and the reduction was judged as partial response. Moreover after 6 courses of FOLFIRI, the reduction was judged as complete response. Local control therapy (S-1+chemo-radiation) plus systemic therapy (FOLFIRI) is one of the promising effective therapies for advanced rectal cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Camptothecin; Drug Combinations; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Proctoscopy; Rectal Neoplasms; Remission Induction; Tegafur; Tomography, X-Ray Computed

The anal sphincter preservation rate (ASPR) according to tumor level and neoadjuvant chemoradiotherpy (CRT) has not been fully evaluated. Therefore, the aim of this study was to evaluate the correlation between the tumor level, neoadjuvant CRT, and the ASPR in rectal cancer patients. We studied 544 patients (tumor level, 0-6 cm) who underwent curative resection for rectal cancer between 1991 and 2005. Patients were divided six into groups according to tumor level over 1-cm intervals, and the ASPR was evaluated in patients with and without neoadjuvant CRT according to tumor level. Sphincter preservation surgery was performed in 191 patients, and 86 patents underwent neoadjuvant CRT. The overall ASPR was 43.0% (37/86) in patients with neoadjuvant CRT and 33.6% (154/458) in patients without neoadjuvant CRT (P=0.094). In an analysis according to tumor level, the ASPR was 0.0 vs 0.0% in

Topics: Adenocarcinoma; Anal Canal; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colectomy; Female; Fluorouracil; Follow-Up Studies; Humans; Injections, Intravenous; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Radiotherapy, Adjuvant; Rectal Neoplasms; Retrospective Studies; Risk Factors; Severity of Illness Index; Treatment Outcome

To evaluate results of preoperative irinotecan/5-FU/leucovorin plus radiotherapy for locally-advanced rectal cancer.. Thirty-five patients with locally-advanced rectal cancer were treated with preoperative irradiation 46 Gy plus concurrent chemotherapy(irinotecan 10 mg/m(2)/d d1-d5, d22-d26, 5-FU 350 mg/m(2)/d d1-d5, d22-d26, and leucovorin 20 mg/m(2) d1-d5, d22-d26), followed by radical surgery.. There were no treatment-related deaths. Acute toxicity was mainly in neutropenia and diarrhea, with both grade 4 neutropenia and grade 3 diarrhea observed in 4 patients(11%). Radical resectability was performed in 29 patients(83%)with sphincter preservation surgery in 7 patients. Six patients did not undergo the planned surgery due to patient refusal and disease progression. A complete pathological response was observed in 14%(4/29). Pathological T-downstaging was observed in 55%(16/29).. These results suggest that preoperative radiochemotherapy with irinotecan/5-FU/leucovorin is safe and effective in tumor downstaging and allows sphincter-saving resection to be performed in locally-advanced rectal cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Disease Progression; Female; Fluorouracil; Follow-Up Studies; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Neoplasm Staging; Rectal Neoplasms; Survival Rate

Although combined-modality therapy (CMT) is the preferred treatment for T3 and/or lymph node (LN)-positive rectal cancer, the German rectal cancer study published in 2004 demonstrated that 18% of patients deemed suitable for preoperative CMT by endorectal ultrasound (ERUS) may be overstaged. Because data also suggest that LN-negative rectal cancer after total mesorectal excision may not require radiotherapy, it is reasonable to consider omitting radiotherapy for the cT3N0 subset. We therefore determined the accuracy of pre-CMT ERUS or magnetic resonance imaging (MRI) staging, to explore the validity of a nonpreoperative CMT approach for cT3N0 disease.. One hundred eighty-eight ERUS-/MRI-staged T3N0 rectal cancer patients received preoperative CMT (fluorouracil based and 45-50.4 Gy) followed by radical resection. Rates of pathologic complete response (pCR) and mesorectal LN involvement were determined.. Tumors were located a median of 5 cm from the anal verge. Sphincter-preserving surgery was performed in 143 patients (76%). Overall pCR was 20%, and 41 patients (22%) had pathologically positive mesorectal LNs. The incidence of positive LNs significantly increased with T stage: ypT0, 3%; ypT1, 7%; ypT2, 20%; ypT3-4, 36% (P = .001).. The accuracy of preoperative ERUS/MRI for staging mid to distal cT3N0 rectal cancer is limited because 22% of patients have undetected mesorectal LN involvement despite CMT. Therefore, ERUS-/MRI-staged T3N0 rectal cancer patients should continue to receive preoperative CMT. Although 18% may be overstaged and therefore overtreated, our data suggest that an even larger number would be understaged and require postoperative CMT, which is associated with significantly inferior local control, higher toxicity, and worse functional outcome.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Cisplatin; Combined Modality Therapy; Endosonography; Female; Fluorouracil; Gamma Rays; Humans; Leucovorin; Lymph Nodes; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Staging; Preoperative Care; Rectal Neoplasms

Oxaliplatin is a third generation platinum compound used in patients with advanced colorectal carcinoma. Recently, the mechanism of a rare drug-induced immune thrombocytopenia in patients receiving oxaliplatin has been described. This complication is caused by oxaliplatin-dependent antibodies directed against platelet surface glycoproteins, and is unrelated to myelosuppression. In this report, we describe two patients who developed thrombocytopenia immediately soon after receiving oxaliplatin. Sensitization presumably had occurred after receiving oxaliplatin during preceding courses of multiagent chemotherapy that included oxaliplatin.

Topics: Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Blood Platelets; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Membrane Glycoproteins; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms; Thrombocytopenia

To determine complete resection and sphincter preservation rates, down-staging, local control and survival associated with concurrent chemoradiotherapy (CCRT) using a moderately high pelvic radiation dose before surgery in rectal cancer.. Fifty-seven patients with histologically proven adenocarcinoma of the mid to lower rectum were treated using preoperative CCRT and surgery. Median radiation dose to the pelvis was 5400 cGy (5040-5580 cGy). CCRT was administered during the first and fifth weeks of radiotherapy with bolus intravenous 5-fluorouracil (5-FU) 400 mg/m(2)/day and leucovorin (LV) 20 mg/m(2)/day for 5 days. Surgery was attempted 4-8 weeks after completing preoperative CCRT. Post-operative chemotherapy was then added for up to four cycles of intravenous 5-FU and LV.. Toxicities during CCRT were generally mild and manageable: Grade 1/2 anemia, 3.5%; Grade 1/2 leukopenia, 45.6%; Grade 3 leukopenia, 3.5%; Grade 1/2 diarrhea, 22.8%; Grade 1/2 abdominal discomfort, 7%; and perianal skin reaction, 5.3%. No late complication requiring surgical intervention occurred. Complete surgical resection with a negative resection margin was achieved in 98.2% of patients, and the down-staging rate was 52.6% (30/57; 95% CI 39.6-65.6%). Complete pathologic response was obtained in 5.3% patients (3/57; 95% CI 0-11.1%) and in other 2 patients only sporadic tumor cells nests were noted in surgical specimens. The sphincter preservation rate was 77.2% (44/57; 95% CI 66.3-88.1%). Of 30 patients with tumors located within 5 cm from the anal verge, sphincter preservation was possible in 18 patients (60.0%; 95% CI 47.3-72.7%). With a median follow-up duration of 40 months, overall and disease-free survival (DFS) rates over 3 years were 91.8% (95% CI 85.5-98.2%) and 79.7% (95% CI 71.2-88.2%), respectively. At univariate analysis, significant factors for DFS was LN involvement status (P = 0.024). Local and distant failure rates over the same period were 5.3 and 21.1%, respectively.. Preoperative CCRT produced encouraging down-staging rates and was found to facilitate complete resection and sphincter saving in distal rectal cancer with acceptable toxicity. Further studies are warranted using this moderately high radiation dose to the pelvis to improve the local control.

Topics: Adenocarcinoma; Adult; Aged; Anal Canal; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Disease-Free Survival; Dose-Response Relationship, Radiation; Drug Administration Schedule; Feasibility Studies; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Radiotherapy, Adjuvant; Rectal Neoplasms; Treatment Outcome

Solid tumors may occur in 3% of the patients with chronic myeloid leukemia (CML). Philadelphia (Ph)-positive CML was diagnosed in a 66-year-old man upon a white blood cell count of 58.1 x 10(9)/L. He had no symptoms and physical findings 3 years after treatment for rectal adenocarcinoma. Imatinib mesylate 400 mg/day was started and white blood cell count was lowered to 5.7 x 10(9)/L in 1 month. The patient had received several chemotherapeutic agents such as 5-fluorouracil, irinotecan, raltitrexed, capecitabine, and oxaliplatin. In the literature, there are two reports on CML after the treatment of colorectal carcinoma. The possibility of a relationship between oxaliplatin and/or irinotecan and CML may not be fully excluded. In conclusion, hematological disorders such as CML may emerge in colorectal carcinoma and whole blood counts should be carefully checked. The possibility of a relationship between CML and the chemotherapeutic agents in colorectal carcinoma should be further evaluated.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Capecitabine; Deoxycytidine; Fluorouracil; Fusion Proteins, bcr-abl; Humans; In Situ Hybridization, Fluorescence; Irinotecan; Leucovorin; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Liver Neoplasms; Male; Neoplasms, Second Primary; Organoplatinum Compounds; Oxaliplatin; Philadelphia Chromosome; Quinazolines; Rectal Neoplasms; Reverse Transcriptase Polymerase Chain Reaction; Thiophenes

A 63-year-old man had undergone a low anterior resection for rectal cancer with multiple liver metastases. Oral UFT (450 mg/day) administration alone was started after the operation. After 6 months post operatively, the patient was diagnosed as anastomosis recurrence because of ileus by abdominal X-ray. Transverse loop colostomy was performed by emergency surgery. After surgery, he suffered from paraplegia for lumbar vertebrae metastases. UFT+LV therapy was started. After chemotherapy a significant reduction of the lymph node and liver metastases and an apparent decrease in CEA and CA19-9 were observed. The patient left the hospital and showed no signs of tumor exacerbation for three months. The patient died of aggravation of primary disease afterwards. The therapy was safe and effective, and has successfully maintained the quality of life (QOL) of this patient.

Topics: Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Bone Neoplasms; Humans; Leucovorin; Lumbar Vertebrae; Magnetic Resonance Imaging; Male; Middle Aged; Rectal Neoplasms; Tegafur; Tomography, X-Ray Computed; Treatment Failure; Uracil

We report a case in which 5-fluorouracil/l-leucovorin (5-FU/l-LV) combination therapy was remarkably effective for non-resectable advanced rectal cancer with multiple liver metastasis. A 68-year-old man complaining of severe abdominal distension and abdominal pain was diagnosed as having ileus due to rectal cancer. We established a diagnosis of non-resectable rectal cancer with multiple liver metastasis and therefore performed only rectal colostomy. Systemic chemotherapy with 5-FU/l-LV was scheduled for a total of 22 courses postoperatively. After the chemotherapeutic regimen, a CT scan and colonofiberscopy revealed the primary lesions had disappeared, and a histological examination of biopsy confirmed that the patient had achieved complete response (CR).

Topics: Aged; Carcinoembryonic Antigen; Colonoscopy; Fluorouracil; Humans; Immunohistochemistry; Leucovorin; Liver Neoplasms; Male; Rectal Neoplasms; Time Factors; Tomography, X-Ray Computed

A 56-year-old woman with multiple lung metastases and lymphangiosis carcinomatosa due to recurrent rectal cancer was treated with chemotherapy of modified FOLFOX6 (mFOLFOX6) regimen: l-leucovorin (l-LV 200 mg/m(2)) and oxaliplatin (L-OHP 85 mg/m(2)) were given as a 2-hour infusion followed by bolus injection of 5-FU 400 mg/m(2) and a 46- hour infusion 5-FU 2,400 mg/m(2) every two weeks. Since partial response was achieved and dyspnea was remarkably improved, she was discharged without oxygen therapy after 5 courses.

Topics: Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Lymphatic Metastasis; Middle Aged; Neoplasm Recurrence, Local; Organoplatinum Compounds; Rectal Neoplasms

A 75-year-old man was referred to our hospital with a diagnosis of lower rectal cancer. Unstable angina attack occurred after admission and cardiac angiography revealed stenosis of three coronary arteries which were treated by percutaneous transluminal coronary angioplasty unsuccessfully. Coronary artery bypass graft was performed after colostomy. It is possible for operative stress, extracorporeal circulation and blood transfusion to diminish immunocompetence and increase the risk of recurrence. Therefore, CPT-11/5-FU/l-LV combination therapy (CPT-11 80 mg/m(2), 5-FU 500 mg/m(2), l-LV 250 mg/m(2) day 1, 8, 15 every 5 weeks) was carried out as neoadjuvant chemotherapy. The tumor decreased in size, and the level of tumor marker was normalized after two courses of the combination therapy. The patient is alive without recurrence three years after abdominoperineal resection.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Coronary Artery Bypass; Coronary Stenosis; Fluorouracil; Humans; Leucovorin; Male; Rectal Neoplasms

To analyze whether the expression of matrix metalloproteinases (MMPs) and their tissue inhibitors are associated with tumor response to preoperative chemoradiotherapy in rectal cancer patients.. Forty-four patients who had undergone preoperative chemoradiotherapy were evaluated retrospectively. Treatment consisted of pelvic radiotherapy and two cycles of 5-fluorouracil plus leucovorin. Surgery was performed 6-8 weeks later. MMP-2, MMP-9, and tissue inhibitors of metalloproteinase-1 and -2 expression was analyzed by immunohistochemistry of the preradiation biopsy and surgical specimens. The intensity and extent of staining were evaluated separately, and a final score was calculated by multiplying the two scores. The primary endpoint was the correlation of expression with tumor response, with the secondary endpoint the effect of chemoradiotherapy on the expression.. Preoperative treatment resulted in downstaging in 20 patients (45%) and no clinical response in 24 (55%). The pathologic tumor response was complete in 11 patients (25%), partial in 23 (52%), and none in 10 (23%). Positive MMP-9 staining was observed in 20 tumors (45%) and was associated with the clinical nodal stage (p = 0.035) and the pathologic and clinical response (p < 0.0001). The staining status of the other markers was associated with neither stage nor response. The overall pathologic response rate was 25% in MMP-9-positive patients vs. 52% in MMP-9-negative patients (p = 0.001). None of the 11 patients with pathologic complete remission was MMP-9 positive.. Matrix metalloproteinase-9 expression correlated with a poor tumor response to preoperative chemoradiotherapy in rectal carcinoma patients.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Logistic Models; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Middle Aged; Neoplasm Proteins; Neoplasm Staging; Rectal Neoplasms; Retrospective Studies; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2

This study was designed to evaluate the prognostic value of circumferential resection margin (CRM) in rectal cancer patients who underwent curative resection with adjuvant chemoradiotherapy (CRT).. We studied 504 patients who underwent total mesorectal excision with adjuvant CRT for rectal cancer between 1997 and 2001. The patients were divided into two groups: a negative CRM group (CRM > 1 mm) and a positive CRM group (CRM

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Chemotherapy, Adjuvant; Colectomy; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Prognosis; Radiotherapy, Adjuvant; Rectal Neoplasms; Rectum; Survival Analysis

To describe our experience with a bolus injection of 5-fluorouracil and leucovorin (FL) vs. capecitabine in terms of radiologic and pathologic findings in preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer.. The study enrolled 278 patients scheduled for preoperative CRT using two protocols with different chemotherapeutic regimens. Pelvic radiotherapy (50.4 Gy) was delivered concurrently with FL (n = 145) or capecitabine (n = 133). Surgery was performed 6 weeks after CRT completion. Tumor responses to CRT were measured using both radiologic and pathologic examination. Magnetic resonance volumetry was performed at the initial workup and just before surgery after completion of preoperative CRT. Post-CRT pathology tests were used to determine tumor stage and regression.. Radiologic examination showed that tumor volume decreased by 68.2% +/- 20.5% in the FL group and 68.3% +/- 22.3% in the capecitabine group (p = 0.970). Postoperative pathologic T stage determination showed that downstaging occurred in 44.3% of FL and 49.9% of capecitabine patients (p = 0.571). The tumor regression grades after CRT were Grade 1 (minimal response) in 22.6% and 21.0%, Grade 2 (moderate response) in 53.2% and 50.0%, Grade 3 (near-complete response) in 12.9% and 12.9%, and Grade 4 (complete response) in 11.3% and 16.1% of the FL and capecitabine groups, respectively (p = 0.758).. In the present study, the radiologic and pathologic findings did not reveal significant differences in short-term tumor responses between preoperative FL and capecitabine CRT for locally advanced rectal cancer. Long-term results and a prospective randomized trial are needed.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Capecitabine; Combined Modality Therapy; Deoxycytidine; Female; Fluorouracil; Humans; Leucovorin; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Staging; Preoperative Care; Radiotherapy Dosage; Rectal Neoplasms; Retrospective Studies

Topics: Adult; Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Fluorouracil; Humans; Kidney Failure, Chronic; Leucovorin; Male; Rectal Neoplasms; Treatment Outcome

We evaluated the efficacy and safety of modified FOLFIRI for patients with refractory advanced or recurrent colorectal cancer. Modified FOLFIRI was given 29 patients (21 men and 8 women, with a median age of 61.0 years) from 2 to 16 times (median 10.0). 19 out of 29 patients were colon cancer, and the other 10 were rectal cancer. 18 patients were administered as first-line chemotherapy, and 11 were more than second line. CPT-11 was administered at a dose of under 150 mg/m(2), to remain within the limits in Japan. The response to treatment was CR in 3 patients, PR in 8, and SD in 12. The response rate was 37.9%. Grade 4 hematologic toxicities included leukocytopenia in 2 patients, neutropenia in 7 and anemia in 1. Grade 3/4 non-hematologic toxicities included febrile neutropenia in 4 patients, anorexia in 3, fatigue in 3, and nausea, diarrhea and interstitial pneumonia in 1. Except in 2 patients, all reactions could be controlled with the use of G-CSF or by setting drug holiday. In summary, modified FOLFIRI is a safe and effective regimen even at a dose of under 150 mg/m(2), of CPT-11. It can be given with good tolerance for patients with refractory advanced or recurrent colorectal cancer on an outpatient basis with due care especially for neutropenia.

Topics: Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Drug Administration Schedule; Feasibility Studies; Female; Fluorouracil; Humans; Infusion Pumps, Implantable; Infusions, Intravenous; Irinotecan; Leucovorin; Leukopenia; Male; Middle Aged; Neutropenia; Quality of Life; Rectal Neoplasms

Patients aged > or = 70 years with colon cancer benefit from chemotherapy, with no major added toxicities compared with a younger population. However, the safety and efficacy of chemotherapy or chemoradiation therapy in octogenarians and nonagenarians with colorectal cancer (CRC) has not been previously reported.. We conducted a retrospective study of the safety and efficacy of chemotherapy or chemoradiation therapy in patients with CRC treated between January 2002 and June 2006 at Roswell Park Cancer Institute.. Thirty-three patients were identified, 24 of whom had colon cancer and 9 of whom had rectal cancer. Twenty-two patients with metastatic colon cancer and 8 patients with rectal cancer were evaluable for toxicity. All patients were started on an attenuated regimen of chemotherapy. A high rate of severe diarrhea (46%) and treatment-related hospitalizations (73%) were noted among patients with metastatic colon cancer. Toxicities were managed by treatment interruptions. The median overall survival among the metastatic colon cancer cohort was 20.6 months (95% confidence interval, 11.1-26.4 months). Among the patients with rectal cancer, 5 had locally advanced disease and were treated with chemoradiation therapy. Chemotherapy was interrupted in 3 of 5 patients because of toxicity. Radiation therapy was discontinued because of toxicity in 1 of 5 patients.. Our results suggest the susceptibility of patients with CRC aged > or = 80 years to chemotherapy toxicity. This age group should receive an attenuated dose of chemotherapy and be evaluated for dedicated clinical trials. Despite the high rate of treatment toxicity, selected octogenarians and nonagenarians with advanced CRC could benefit from chemotherapy, with overall survival neighboring that seen in younger populations.

Topics: Age Factors; Aged, 80 and over; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Capecitabine; Colonic Neoplasms; Combined Modality Therapy; Deoxycytidine; Female; Fluorouracil; Humans; Leucovorin; Male; Rectal Neoplasms; Retrospective Studies; Survival; Treatment Outcome

We have treated 14 advanced and metastatic colorectal cancers with irinotecan (CPT-11) plus fluorouracil (5-FU) and l-leucovorin (l-LV) combination chemotherapy. The 14 patients consisted of 8 males and 6 females with a mean age of 65 years. We diagnosed adenocarcinoma of the colon in 10 patients and of the rectum in 4 patients. Four patients had liver metastases, five had lung metastases, and one had both, while one had lung and lymph node metastases, two had lymph node metastases and one had a local recurrence. The chemotherapy consisted of CPT-11 100 mg/m(2) div, as a 150-minute infusion, simultaneously l-LV 10 mg/m(2) div, as a 30-minute infusion, followed by 5-FU 500 mg/m(2) iv, as a bolus injection. This treatment was administered weekly for 2 weeks followed by a 2-week rest period and repeated every 4 weeks. All patients received this regimen as first-line chemotherapy. All patients were evaluated for efficacy 1 CR, 2 PR, 9 SD, and 2 PD. The overall response rate was 21.4% with a median time to progression of 8.1 months and a median survival time of 18.6 months. Grade 3 nausea, diarrhea and the suppression of white blood cells were seen in 3 patients, respectively. All other adverse reactions were mild (grade 1 or 2). Except for one patient,residual patients were able to receive the systemic chemotherapy on schedule. CPT-11/5-FU/l-LV combination chemotherapy appears to be effective first-line chemotherapy for advanced and metastatic colorectal cancer.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Rectal Neoplasms; Retrospective Studies

A 72-year-old man was admitted to our hospital, complaining of severe diarrhea. Computed tomography, barium enema and colonoscopy revealed a cysto-rectal fistula and massive invasion to middle rectum and retroperitoneal space from the main tumor in the upper rectum. Because of obstruction of passage of stool, sigmoid colostomy was performed. Oral UFT/LV+CPT-11 were undertaken after surgery for 4 cycles to remarkably reduce the tumor both clinically and on an outpatient basis. During this period, no side effect was detected, and a performance status (PS) of 0 has been maintained. As the result, radical resection was performed 5 months after the first operation. The histological effect was judged to be grade 2. Furthermore, no recurrence was recognized after 16 months postoperatively. Therefore, oral administration of UFT/LV+CPT-11 was considered as effective neoadjuvant chemotherapy for advanced rectal carcinoma, and this also could be a promising regimen to maintain the quality of life (QOL) for patients in ambulatory therapy.

Topics: Adenocarcinoma; Administration, Oral; Aged; Ambulatory Care; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Drug Administration Schedule; Drug Combinations; Humans; Irinotecan; Leucovorin; Male; Neoadjuvant Therapy; Neoplasm Invasiveness; Pelvic Neoplasms; Quality of Life; Rectal Neoplasms; Tegafur; Uracil

Considerable progress has been made in improving disease-free survival in stage III colon cancer with the use of adjuvant chemotherapy. In recent years, it has been shown that infusional 5-fluorouracil regimens maintain the efficacy and reduce toxicity associated with bolus 5-fluorouracil, that improved tolerability can be achieved with use of the oral fluoropyrimidine capecitabine, and that improved efficacy can be achieved by combining 5-fluorouracil/leucovorin with other cytotoxic agents (eg, oxaliplatin and irinotecan). Studies are ongoing to identify optimal adjuvant regimens in stage II or III disease and to identify the potential benefits of adding bevacizumab or cetuximab to adjuvant therapy.

Topics: Antibodies, Monoclonal; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Capecitabine; Colonic Neoplasms; Deoxycytidine; Disease-Free Survival; Fluorouracil; Humans; Irinotecan; Leucovorin; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Prodrugs; Rectal Neoplasms; Vitamin B Complex

We performed a retrospective analysis in order to evaluate the compliance with preoperative radiotherapy in patients aged>or=70 with locally advanced resectable rectal cancer, and to evaluate the influence of comorbidities on treatment tolerance and oncological results.. From March 1984 to December 2000, 95 patients with T3-T4 N0 M0 rectal cancer received a preoperative radiotherapy in 2 radiotherapy departments. Nineteen patients received concomitant chemotherapy.. All patients completed the radiation schedule. Six patients suffered grade 3 acute WHO toxicity. Surgical resection was performed in 87 patients. There were 3 post-operative deaths. Analysis of peri-operative complications showed thromboembolism (4.9%), ileus (9.8%) and diarrhoea (6.1%). After a median follow-up of 29 months, the 3- and 5-year overall survival rates were 65% and 49% respectively. In univariate analysis, a tumour located in the mid part of the rectum, a radiation dose less than 40 Gy, the absence of chemotherapy were significantly associated with a poor prognosis. There was a trend to a better survival for patients with a Charlson score of 0 (P=0.0584). In multivariate analysis, only initial WHO performance status was significant.. Compliance with preoperative radiotherapy is good in elderly patients. Toxicity rates are similar to those described in randomised trials in which only younger patients were included. Initial WHO performance status

Topics: Age Factors; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; APACHE; Chi-Square Distribution; Combined Modality Therapy; Data Interpretation, Statistical; Female; Fluorouracil; Follow-Up Studies; Humans; Karnofsky Performance Status; Leucovorin; Male; Neoplasm Staging; Postoperative Complications; Preoperative Care; Prognosis; Radiotherapy; Radiotherapy Dosage; Radiotherapy, Adjuvant; Rectal Neoplasms; Rectum; Retrospective Studies; Risk Factors; Survival Analysis; Time Factors; Vitamin B Complex; World Health Organization

Preoperative chemoradiotherapy has demonstrated to improve resectability and local control in locally advanced rectal cancer (LARC). 5-fluorouracil (5FU) has traditionally been the drug of choice in combination with radiation therapy. Early studies of capecitabine (CAP) have shown its potential to replace 5FU. Between March 2002 and April 2005, 31 patients with newly diagnosed LARC (T2 N+ 2 cases, T3 N0-N+ 25 cases, T4 N0-N+ 4 cases) received the combined treatment. Surgery was planned 6-8 weeks after chemoradiation. Adjuvant chemotherapy with 5FU plus leucovorin for 6 courses was given in pN+ patients. All patients completed the planned treatment. Grade 3 acute toxicity was observed in 5 patients (16%). Nineteen patients (61%) had a downstaging. A complete pathological remission was observed in 3 cases (10%). Median follow-up is of 23 months (range; 6-36 months). The results of this experience confirm the data of the literature about the feasibility and efficacy of a neoadjuvant treatment with radiation and CAP in LARC.

Topics: Adenocarcinoma; Adult; Aged; Antimetabolites, Antineoplastic; Capecitabine; Chemotherapy, Adjuvant; Combined Modality Therapy; Deoxycytidine; Digestive System Surgical Procedures; Feasibility Studies; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Lymph Node Excision; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Invasiveness; Radiotherapy, Adjuvant; Rectal Neoplasms; Treatment Outcome; Vitamin B Complex

Chemotherapy alone without a multimodality approach has never been demonstrated to cure metastatic colorectal cancer patients. We report the case of a young woman referred in 1999 to our institution for a pelvic relapse of rectal cancer remained stable after oxaliplatin, 5-fluorouracil, and folinic acid therapy and never grown in size up to now, more than 6 years after the last relapse. Death of all the cancer cells, neuroendocrine cells selection, or cell dormancy are some of the discussed explanations to this unique observation. An intriguing question remains open: Should this patient be considered cured?

Topics: Adenocarcinoma; Adult; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Leucovorin; Neoplasm Recurrence, Local; Organoplatinum Compounds; Oxaliplatin; Pelvis; Rectal Neoplasms; Tomography, X-Ray Computed; Treatment Outcome

A 56-year-old man was hospitalized for anemia with appetite loss and body weight loss. He was diagnosed as advanced sigmoid colon cancer which invaded the rectal colon (Ra) and prostate (SI, N 0, P 0, H 0, M (-), cStage IIIa). We administered neoadjuvant chemoradiotherapy for fear of non-curative resection of the sigmoid colon and rectum after colostomy was performed. He was given radiation of the whole pelvis at a total dose of 39 .6 Gy (1.8 Gy x 22 times) combined with chemotherapy using continuous intravenous 5-FU (500 mg x 22 times). Two weeks after the chemoradiation, we administered chemotherapy (FOLFOX 4). Resectable resection was confirmed on Computed Tomography. We were able to conduct a low anterior resection of sigmoid colon and rectum. Postoperative histopathological examination of the resected sigmoid colon and rectum revealed no remnant cancer tissue. Neo-adjuvant chemoradiotherapy is considered to be effective for a study of non-curative resection of rectum.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Drug Administration Schedule; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Invasiveness; Organoplatinum Compounds; Prostatic Neoplasms; Radiotherapy, Adjuvant; Rectal Neoplasms; Sigmoid Neoplasms

There are a few clinical trials of combination chemotherapy of oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX-4) in Japan, and its efficacy and safety have not been confirmed yet, especially clinical experience in patients with prior chemotherapy.. To analyze the efficacy and safety of FOLFOX-4 in patients with colorectal cancer who received prior chemotherapy.. Twenty patients were treated with FOLFOX-4 beginning in April 2005. Three patients were entered into the safety study, and seventeen patients were treated on a reduced dose, because they had already received heavy doses of prior chemotherapy.. Number of prior chemotherapy was 1 regimen in 7 patients, more than two regimens in 13 patients. The median course of FOLFOX-4 was 10 (4-12), which gave an overall response rate of 20.0% and a median time to progression of 5.0 months. The median survival time was 15.6 months from initiation of the FOLFOX-4, and 28.5 months from the first-line treatment. Grade 3/4 neutropenia was seen in 12 patients (60%), and neuropathy was observed in 11 patients (55%). No response was seen in irinotecan based regimens after FOLFOX-4.. FOLFOX-4 in patients with pretreated colorectal cancer was effective, and contributed to prolonged life with the TTP of 5 months. However, hematological toxicity was high despite the reduced dose. Further extension of prolonged life is anticipated by administering incorporating molecular targeting agents.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Drug Administration Schedule; Fatigue; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Liver Neoplasms; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neutropenia; Organoplatinum Compounds; Rectal Neoplasms; Salvage Therapy; Survival Rate

Topics: Adenocarcinoma; Adult; Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colitis, Ischemic; Colonoscopy; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Rectal Neoplasms

To investigate the effect of preoperative radiotherapy or chemoradiotherapy on the sphincter preservation and local tumor control as well as survival for the patient with locally advanced middle-low rectal cancer.. 121 locally advanced middle-low rectal cancer patients were treated with preoperative radiotherapy or chemoradiotherapy followed by surgery after rest of 4 to 6 weeks. 103 of these patients who underwent radical surgery were finally included in this study. The irradiation regimen was: 40 Gy/4 - 5 weeks, whereas 57 of these 103 patients received concurrent chemotherapy of 5-Fu or Xeloda. Sphincter-preserving surgery was performed in 59 patients and abdominoperineal resection in 44 patients. The survival was estimated by Kaplan-Meier model, and the differences between groups were compared using Log rank test. Multivariate analysis was performed by Cox's model.. Ten patients (9.7%) achieved a complete pathological response (pCR) to preoperative radiotherapy or chemoradiotherapy. The sphincter preservation rate was 57.3%. The 3-year overall survival (OS) and disease free survival (DFS) was 66.3% and 59.5%, respectively. Univariate analysis showed that pCR and postoperative pTNM stage were prognostic factors affecting survival, whereas, only pTNM stage was an independent prognostic factor (P = 0.003) by multivariate analysis.. Neoadjuvant preoperative radiotherapy and chemoradiotherapy is effective in local tumor control and improving survival for locally advanced middle-low rectal cancer, which can raise the rate of sphincter-preserving surgery, and achieve comparable result to abdominoperineal resection.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Combined Modality Therapy; Deoxycytidine; Female; Fluorouracil; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Multivariate Analysis; Neoadjuvant Therapy; Particle Accelerators; Preoperative Care; Radiotherapy, High-Energy; Rectal Neoplasms; Retrospective Studies

This analysis assesses the efficacy and safety of a modified FOLFOX (oxaliplatin/leucovorin [LV]/5-fluorouracil [5-FU]) regimen given with a low dose of LV.. Forty patients with previously untreated metastatic colorectal cancer were enrolled to receive every-2-week cycles of oxaliplatin 100 mg/m(2) intravenously administered over 2 hours concurrently with LV 20 mg/m(2) bolus and 5-FU 400 mg/m(2) bolus, followed by a 46-hour infusion of 5-FU 2.4 g/m(2).. Thirty-nine patients received > or = 1 oxaliplatin dose and a median of 10 treatment cycles (range, 1-13 cycles). Thirteen patients (34%) experienced grade 3/4 neutropenia, whereas 21% of patients experienced grade 3 neurotoxicity. Of 37 eligible patients, complete or partial responses were observed in 18 patients (49% [95% confidence interval (CI), 32%-66%]). The median progression-free survival was 6.2 months (95% CI, 5.5-8.7 months) with a median overall survival of 14.2 months (95% CI, 10-20.5 months).. A modified schedule of FOLFOX using a lower than standard dose of LV provides good response and survival results with excellent safety. A comparison with a previous study undertaken in the same centers using identical inclusion/exclusion criteria but using higher doses of LV suggests that reducing the dose of LV improves safety without compromising efficacy.

Topics: Adenocarcinoma; Adult; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Dose-Response Relationship, Drug; Female; Fluorouracil; Humans; Leucovorin; Male; Neoplasm Staging; Organoplatinum Compounds; Rectal Neoplasms; Survival Rate

Combination therapy of irinotecan, leucovorin (LV), and 5-fluorouracil (5-FU)(FOLFIRI regimen) has certain effect on advanced colorectal cancer. However, data of this regimen as first-line chemotherapy for Chinese patients with advanced colorectal cancer is still lacking, and its efficacy and safety still needs to be defined. This study was to explore the efficacy of FOLFIRI regimen as first-line chemotherapy on advanced colorectal cancer in Chinese patients, and observe its safety.. Clinical data of 54 chemotherapy-naive patients with advanced colorectal cancer, treated with FOLFIRI regimen from Jan. 2002 to Sep. 2005 in Cancer Center of Sun Yat-sen University, were analyzed.. Of the 54 patients, 52 were evaluable for response. The overall response rate was 42.6%, the time to progression (TTP) was 6 months, and the overall survival time was 15.2 months. The most common drug-related adverse events were neutropenia (38.9%), diarrhea (37.1%) and nausea and vomiting (50.0%). The occurrence rates of these grade 3-4 events were 5.6%, 9.3%, and 9.3%, respectively. All adverse events were tolerable.. FOLFIRI regimen is effective and well-tolerated as first-line treatment for Chinese patients with advanced colorectal cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Diarrhea; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Nausea; Neoplasm Staging; Neutropenia; Rectal Neoplasms; Remission Induction; Retrospective Studies; Survival Rate; Young Adult

Active anticancer drugs and/or combination regimens for the treatment of patients failing oxaliplatin, irinotecan and 5-fluorouracil are desperately needed. In this analysis we describe the safety and efficacy of the combination of mitomycin C, UFT and leucovorin in such an extensively pretreated patient population. Between January 2002 and June 2004, a total of 41 patients were treated with mitomycin C (8 mg/m on day 1) and UFT (350 mg/m)+ leucovorin (90 mg) both divided into three daily doses from day 1 to day 14 every 4 weeks. All patients had failed prior first-line and second-line treatment with oxaliplatin, irinotecan and 5-fluorouracil. The aim of this retrospective analysis was to evaluate the efficacy and safety data of this potential salvage therapy regimen. Thirty-nine patients were evaluable for the response. The overall response rate (intent-to-treat) was 7.3% (95% confidence interval, 2.5-19.4%) and disease stabilization was achieved in 29.3%. Median time to progression was 2.5 months (range, 1.5-13.5) and median overall survival was 6 months (range, 1.5-26). Myelosuppression was the most frequent side effect. Grade 3 hematotoxicity, however, was observed in only three patients. The most common nonhematological toxicities consisted of mild and reversible nausea, emesis and diarrhea; again, severe symptoms were only occasionally seen. These data show that the combination of mitomycin C/UFT/leucovorin is safe and active in about one-third of patients in terms of abrogation of progression in extensively pretreated metastatic colorectal cancer.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Disease Progression; Disease-Free Survival; Female; Humans; Leucovorin; Male; Middle Aged; Mitomycin; Neoplasm Metastasis; Rectal Neoplasms; Retrospective Studies; Salvage Therapy; Tegafur; Uracil

Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Female; Fluorouracil; Humans; Hypotension; Leucovorin; Liver Neoplasms; Middle Aged; Rectal Neoplasms

To assess factors affecting long-term survival of patients undergoing radiofrequency ablation (RFA) of colorectal hepatic metastases, with attention to evolving chemotherapy regimens.. Prospective evaluation of 235 patients with colorectal metastases who were not candidates for resection and/or failed chemotherapy underwent laparoscopic RFA. Preoperative risk factors for survival and pre- and postoperative chemotherapy exposure were analyzed.. Two hundred and thirty-four patients underwent 292 RFA sessions from 1997 to 2006, an average of 8 months after initiation of chemotherapy. Twenty-three percent had extrahepatic disease preoperatively. Patients averaged 2.8 lesions, with a dominant diameter of 3.9 cm. Kaplan-Meier actuarial survival was 24 months, with actual 3 and 5 years survival of 20.2% and 18.4%, respectively. Median survival was improved for patients with 3 lesions (27 vs. 17 months, P=0.0018); dominant size<3 versus >3 cm (28 vs. 20 months, P=0.07); chorioembryonic antigen<200 versus >200 ng/mL (26 vs. 16 months, P=0.003). Presence of extrahepatic disease (P=0.34) or type of pre/postoperative chemotherapy (5-FU-leucovorin vs. FOLFOX/FOLFIRI vs. bevacizumab) (P=0.11) did not alter median survival.. To our knowledge, this is both the largest and longest follow-up of RFA for colorectal metastases. The number and dominant size of metastases, and preoperative chorioembryonic antigen value are strong predictors of survival. Despite classic teaching, extrahepatic disease did not adversely affect survival. In this group of patients who failed chemotherapy, newer treatment regimens (pre- or postoperatively) had no survival benefit. The actual 5-year survival of 18.4% in these patients versus near zero survival for chemotherapy alone argues for a survival benefit of RFA.

Topics: Adenocarcinoma; Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Carcinoembryonic Antigen; Catheter Ablation; Chemotherapy, Adjuvant; Cohort Studies; Colonic Neoplasms; Female; Fluorouracil; Follow-Up Studies; Humans; Laparoscopy; Leucovorin; Liver Neoplasms; Longitudinal Studies; Male; Middle Aged; Organoplatinum Compounds; Prospective Studies; Rectal Neoplasms; Risk Factors; Survival Rate; Treatment Outcome; Vitamin B Complex

The FOLFIRI regimen (irinotecan in combination with bolus and continuous infusion of 5-FU and l-LV) and FOLFOX regimen (oxaliplatin/5-FU/LV therapy) are now standard chemotherapy for metastatic colorectal cancer in Western countries. Combining those regimens, a median overall survival time (MST) of over 20 months has been reached. However, adverse reactions related to those regimens have included deteriorating patient quality of life (QOL). Here, we report a case of metastatic rectal cancer showing a complete response (CR) to cycle 4 in FOLFIRI regimen, while maintaining a CR status for over 11 months and good QOL, as a result of chemotherapy with 4 cycles of FOLFIRI followed by UFT.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Female; Fluorouracil; Humans; Leucovorin; Neoplasm Metastasis; Rectal Neoplasms; Tegafur; Uracil

Combination chemotherapy of oxaliplatin, fluorouracil/leucovorin (FOLFOX) has reportedly become a standard regimen for colorectal cancer. In this study, we investigated the efficacies and adverse effects of modified FOLFOX6 (m-FOLFOX6) regimen in elderly patients. Thirty-nine patients with colorectal cancer, who received m-FOLFOX6 in our institution, were studied. Ten of the 39 patients, were older than 70 (elderly patients). Efficacies and adverse effects of m-FOLFOX6 were compared between patients over 70 years of age and those younger than 69 (younger patients). In terms of the response rate, there were no differences between the older and younger elderly patients. Moreover, the grade and frequency of adverse events were similar between them. We concluded that m-FOLFOX6 may bring about the same response rate in older and younger elderly patients. Moreover, m-FOLFOX6 may be given safely regardless of patient age.

Topics: Age Factors; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Organoplatinum Compounds; Rectal Neoplasms; Remission Induction

We performed FOLFOX 4 therapy in a patient with lung metastasis (a 62-year-old woman) after surgery for rectal cancer and observed both normalization of tumor markers and disappearance of the metastasis. Low anterior resection was performed for progressive rectal cancer, and treatment with UFT and folinate was started one month after surgery. However, tumor markers increased after 2 months of treatment and CT scans showed metastases to both lungs. FOLFOX 4 therapy was started, and tumor markers became normal after four courses, while the lung metastases disappeared after 10 courses. The dosage of FOLFOX 4 was reduced after three courses due to neutropenia and diarrhea. This treatment appeared to be effective for the inhibition of lung metastasis associated with colorectal cancer.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Combined Modality Therapy; Drug Administration Schedule; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Lung Neoplasms; Middle Aged; Organoplatinum Compounds; Rectal Neoplasms

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoid Tumor; Chemotherapy, Adjuvant; Disease-Free Survival; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Middle Aged; Rectal Neoplasms; Rectum; Remission Induction; Soft Tissue Neoplasms; Time Factors; Treatment Outcome

The patient presented here is a 30-year-old woman who underwent anterior resection for the initial treatment of rectal cancer. A postoperative study showed a single liver metastasis. The patient received adjuvant pelvic radiotherapy with concomitant 5-fluorouracil (5-FU) treatment followed by liver metastasectomy 6 weeks after the completion of radiation therapy and chemotherapy. Adjuvant therapy with 5-FU, leucovorin, and oxaliplatin (FOLFOX 4 regimen) was continued. The initial five cycles were well tolerated with the occurrence of only paresthesia that did not interfere with function. After the sixth cycle of the treatment, progressive dyspnea and persistent cough developed in the patient, although her clinical history was negative for lung disease. A chest radiograph revealed diffuse bilateral interstitial infiltrates, and a chest CT scan showed bilateral alveolar infiltrates predominant in the right lung. Lung biopsy by video-assisted thoracoscopy was performed, and the histologic report showed cryptogenic organizing pneumonitis (COP). Prednisone therapy (1 mg/kg/d) resulted in a very good clinical response. In fact, the patient had complete remission of respiratory symptoms including cough and dyspnea after 4 days of treatment, and the chest CT scan showed complete resolution of lung infiltrates after 4 weeks. One month later, the patient continued adjuvant treatment with six cycles of 5-FU, leucovorin, and irinotecan (ie, the FOLFIRI regimen) without complications. Thus, oxiplatin was implicated as the likely cause of this drug-induced lung toxicity, which is a very rare complication associated with platins. Diffuse interstitial lung disease, particularly COP, has been described following the administration of the cytotoxic agents bleomycin and busulfan, but a connection to oxaliplatin has not been reported before this case.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Camptothecin; Cryptogenic Organizing Pneumonia; Female; Fluorouracil; Glucocorticoids; Humans; Leucovorin; Liver Neoplasms; Organoplatinum Compounds; Oxaliplatin; Prednisone; Radiotherapy, Adjuvant; Rectal Neoplasms; Thoracic Surgery, Video-Assisted; Tomography, X-Ray Computed

Topics: Algorithms; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Digestive System Surgical Procedures; Dose Fractionation, Radiation; Drug Administration Schedule; Fluorouracil; Follow-Up Studies; Humans; Hyperthermia, Induced; Leucovorin; Radiotherapy, Adjuvant; Rectal Neoplasms; Retrospective Studies; Survival Analysis; Treatment Outcome

Topics: Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Colonoscopy; Endoscopy; Female; Fluorouracil; Follow-Up Studies; Humans; Laparoscopy; Leucovorin; Male; Neoplasm Recurrence, Local; Neoplasm Staging; Palliative Care; Radiotherapy Dosage; Radiotherapy, Adjuvant; Rectal Neoplasms; Rectum; Vitamin B Complex

A worsened anorectal function after chemoradiation for high-risk rectal cancer is often attributed to radiation damage of the anorectum and pelvic floor. Its impact on pudendal nerve function is unclear. This prospective study evaluated the short-term effect of preoperative combined chemoradiation on anorectal physiologic and pudendal nerve function.. Sixty-six patients (39 men, 27 women) with localized resectable (T3, T4, or N1) rectal cancer were included in the study. All patients received 45 Gy (1.8 Gy/day in 25 fractions) over five weeks, plus 5-fluorouracil (350 mg/m2/day) and leucovorin (20 mg/m2/day) concurrently on days 1 to 5 and 29 to 33. Patients who had rectal cancer with a distal margin within 6 cm of the anal verge had the anus included in the field of radiotherapy (Group A, n = 26). Patients who had rectal cancer with a distal margin 6 to 12 cm from the anal verge had shielding of the anus during radiotherapy (Group B, n = 40). The Wexner continence score, anorectal manometry and pudendal nerve terminal motor latency were assessed at baseline and four weeks after completion of chemoradiation.. The median Wexner score deteriorated significantly (P < 0.0001) from 0 to 2.5 for both Groups A (range, 0-8) and B (range, 0-14). The maximum resting anal pressures were unchanged after chemoradiation. The maximum squeeze anal pressures were reduced (mean = 166.5-157.5 mmHg) after chemoradiation. This change was similar in both Groups A and B. Eighteen patients (Group A = 7, Group B = 11) developed prolonged pudendal nerve terminal motor latency after chemoradiation. These 18 patients similarly had a worsened median Wexner continence score (range, 0-3) and maximum squeeze anal pressures (mean = 165.5-144 mmHg). The results obtained were independent of tumor response to chemoradiation.. Preoperative chemoradiation for rectal cancer carries a significant risk of pudendal neuropathy, which might contribute to the incidence of fecal incontinence after restorative proctectomy for rectal cancer.

Topics: Adenocarcinoma; Adult; Aged; Antimetabolites, Antineoplastic; Biopsy; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Manometry; Middle Aged; Motor Neurons; Peripheral Nervous System Diseases; Preoperative Care; Pressure; Prospective Studies; Radiotherapy, Adjuvant; Rectal Neoplasms; Rectum; Risk Factors; Vitamin B Complex

Patients with bilobar colorectal cancer metastases to the liver present a unique problem in terms of resection. They sometimes require a staged approach to resection that takes advantage of the liver's ability to regenerate, as well as the newer chemotherapeutic agents (e.g., oxaloplatin, irinotecan (CPT-11), and bevacizumab) that have become available. In cases of multiple bilobar metastases, if segment IV is clear of tumor, a left lateral segmentectomy (LLS) can be performed, followed several months later by a formal right hepatectomy. The remnant liver composed of the hypertrophied segment IV is drained by the middle hepatic vein (MHV). In this context, patients with lesions between the origin of the MHV and the inferior vena cava (IVC) present a particularly difficult problem. Conventional excision would require an extended hepatectomy and division of the MHV along with either the right or left hepatic veins (RHV, LHV). This would make it impossible to continue with a formal resection of the remaining lesions in the contralateral liver without sacrificing the sole remaining hepatic vein. We present a novel two-step hepatectomy for lesions between the MHV and the IVC that allows the MHV to be preserved and all lesions to be resected.

Topics: Adenocarcinoma; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Camptothecin; Chemotherapy, Adjuvant; Colonic Neoplasms; Fluorouracil; Follow-Up Studies; Hepatectomy; Hepatic Veins; Humans; Irinotecan; Leucovorin; Liver; Liver Neoplasms; Liver Regeneration; Male; Rectal Neoplasms; Vena Cava, Inferior

We report a case in which l-Leucovorin/5-fluorouracil (l-LV/5-FU) therapy was remarkably effective for advanced rectal cancer as neoadjuvant chemotherapy (NAC). A 54-year-old man complained of bloody stool and constipation,and was diagnosed as having stage IIIB advanced rectal cancer with N2 lymphnode metastases on July 31, 2003. Two cycles of NAC by l-LV/5-FU therapy were performed. On abdominal computed tomography (micro CT), the primary lesion in the rectum decreased 82% and the metastatic lymphnodes had disappeared. As we established a diagnosis of the downstaging for stage II, a lower anterior resection with D3 lymphnode dissection was performed on December 5, 2003. The pathological examination demonstrated II, mod, 1.8 x 2.2 cm, a1, ly1,v0, ow(-), aw(-), n0, stage II. We could allow curability-A resection. The pathological effect of chemotherapy was grade 2 in which cancer cells became necrotic, suggesting apoptosis. The postoperative course was good. Postoperatively, 3 cycles of l-LV/5-FU therapy were performed. Although the patient had to be followed with internal use of 5-FU 200 mg/day as an outpatient from June 2, 2004, to date, there has been no sign of recurrence during the 12-month follow-up after the operation. Moreover, no adverse by chemotherapy was seen during the treatment. Thus, NAC by this therapy may be useful for patients with advanced rectal cancer.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Drug Administration Schedule; Fluorouracil; Humans; Leucovorin; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Rectal Neoplasms

To compare efficacy in terms of pathologic response in LARC patients treated with preoperative chemoradiation, with or without a short-intense course of induction oxaliplatin.. From 05/98 to 10/02, 114 patients were treated with preoperative chemoradiation (4500-5040 cGy + oral Tegafur 1200 mg/day) for cT(3)-(4)N(+/x)M(0) rectal cancer. Starting 05/01, 52 consecutive patients additionally received induction FOLFOX-4, oxaliplatin (85 mg/m(2) iv d1), 5-FU (400 mg/m(2) iv bolus d1) and 600 mg/m(2) iv continuous infusion in 22 h with leucovorin (200 mg iv) d1 and d2, every 15 days (2 cycles), followed by the previously described Tegafur chemoradiation regime. Surgery was performed in 5-6 weeks. Pathological assessment investigated post-treatment T and N status in the rectal wall and peri-rectal tissues.. Patients, tumor and treatment characteristics were comparable between groups. Incidence of pT(0) specimens was significantly increased by induction FOLFOX-4 (P = 0.006). Total T and N downstaging were 58% versus 75% and 42% versus 40%, respectively (P = ns). T downstaging of > or =2 categories was significantly superior in FOLFOX-4 group (P = 0.029).. Short-intense induction FOLFOX-4 significantly improves pathologic complete response in LARC patients treated with tegafur-sensitized preoperative chemoradiation. The 44% rate of pT(0)-(1) specimens observed in the oxaliplatin group should impulse innovative surgical approaches to promote ano-rectal sphincter conserving protocols.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Preoperative Care; Radiotherapy Dosage; Rectal Neoplasms; Tegafur

Liver is the most common site of metastasis in colorectal cancer, and 35% patients with colorectal cancer developed liver metastasis at diagnosis. The prognosis of the patients with liver metastases from colorectal cancer is poor. Surgical resection, radiofrequency ablation, and chemotherapy had been used in clinical treatment for liver metastasis from colorectal cancer with various outcomes. This study was to explore the treatment efficacy of surgical management for liver metastasis from colorectal cancer.. Clinical data of 198 patients with liver metastasis from colorectal cancer, treated from Jan. 1995 to Jan. 2000, were studied retrospectively. Of the 198 patients, 46 (23.2%) received radical resection, 43 (21.7%) received palliative resection, 29 (14.6%) received exploratory operation or supportive treatment, 41 (20.7%) received adjuvant hepatic arterial infusion, and 39 (19.7%) received adjuvant systemic chemotherapy. Survival statuses of the patients in different groups were compared.. The median survival time of radical resection group was significantly longer than those of palliative resection group, exploratory operation or supportive treatment group, adjuvant hepatic arterial infusion group, and adjuvant systemic chemotherapy group (37.1 months vs. 14.3, 6.3, 21.3, and 18.7 months, P<0.01). The 5-year survival rates of the 5 groups were 31.2%, 0, 0, 7.5%, and 0, respectively.. Radical resection could improve survival of the patients with liver metastasis from colorectal cancer. Palliative resection has no advantage over adjuvant therapy. Adjuvant hepatic arterial infusion should be applied in the unresectable cases.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colonic Neoplasms; Female; Fluorouracil; Follow-Up Studies; Hepatectomy; Humans; Infusions, Intra-Arterial; Leucovorin; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Organoplatinum Compounds; Prognosis; Rectal Neoplasms; Retrospective Studies; Survival Rate; Treatment Outcome

To report the retrospective analysis of patients with locally advanced rectal cancer treated with neodjuvant radiochemotherapy.. From January 1994 to December 2003, 101 patients with fixed (25%) or semi-fixed (75%) rectal adenocarcinoma were treated by preoperative radiotherapy with a dose of 45 Gy at the whole pelvis and 50.4 Gy at primary tumor, concomitant to four weekly chemotherapies with 5-Fluorouracil (425 mg/m2) and Leucovorin (20 mg/m2). In 71 patients (70.3%) the primary tumor was located up to 6 cm from the anal verge and in 30 (29.7%) from 6.5 cm to 10 cm. Age, gender, tumor fixation, tumor distance from the anal verge, clinical response, surgical technique, and postoperative TNM stage were the prognostic factors analyzed for overall survival (OS), disease-free survival (DFS), and local control (LC) at five years.. Median follow-up time was 38 months (range, 2-141). Complete response was observed in eight patients (7.9%), partial in 54 (53.4%) and absence in 39 (38.7%). OS, DFS and LC were 52.6%, 53.8%, and 75.9%, respectively. Distant metastasis occurred in 40 (39.6%) patients, local recurrence in 20 (19.8%) and both in 16 (15.8%). Patients with fixed tumors had lower OS (17% Vs 65.6%; p < 0.001), DFS (31.2% Vs 60.9%; p = 0.005), and LC (58% Vs 82%; p = 0.004). Patients with tumors more than 6 cm above the anal verge had better LC (93% Vs 69%; p = 0.04). The postoperative TNM stage was a significant factor for DFS (I:64.1%, II:69.6%, III:35.2%, IV:11.1%; p < 0.001) and for LC (I:75.7%, II: 92.9%, III:54.1%, IV:100%; p = 0.005). Patients with positive lymph nodes had worse OS (37.9% Vs 70.4%, p = 0.006), DFS (32% Vs 72.7%, p < 0.001) and LC (56.2% Vs 93.4%; p < 0.001).. This study suggests that the neoadjuvant treatment employed was effective for local control. Fixation of the lesion and lymph nodes metastasis were the main adverse prognostic factors. Distant failures were frequent, supporting the need of new drugs for adjuvant chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Chemotherapy, Adjuvant; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Prognosis; Radiotherapy; Rectal Neoplasms; Retrospective Studies

Patients with locally advanced rectal cancer (LARC) have a poor prognosis. Preoperative radiotherapy may shrink the tumour and make subsequent resection possible. The use of modern principles of preoperative radiotherapy in combination with chemotherapy and an active surgical attitude increases the chance for radical surgery and cure.. A single-institution, prospective evaluation of a new treatment strategy in patients with LARC was done.. From 1998 to 2000, 20 patients with LARC were treated with high-dose radiochemotherapy (60 Gy and chemotherapy, UFT/leucovorin), and resectability was evaluated four to six weeks after termination of radiochemotherapy. Sixty percent of the patients subsequently had microscopic radical surgery.. Patients with LARC should preferably be treated with high-dose preoperative radiotherapy in combination with chemotherapy. Evaluation of resectability should be performed at least four weeks after termination of radiotherapy. This strategy, in combination with modern surgical techniques, increases the probability of success of radical surgery and cure.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Humans; Leucovorin; Male; Middle Aged; Preoperative Care; Prognosis; Prospective Studies; Radiotherapy Dosage; Rectal Neoplasms; Tegafur; Uracil; Vitamin B Complex

Pharmacokinetic modulating chemotherapy (PMC) is designed to boost high serum 5-fluorouracil (5-FU) concentrations via modulation by uracil. The aim of this study was to evaluate the efficacy of PMC as a second-line chemotherapy for postresectional recurrences of colorectal carcinoma.. Thirteen patients with unresectable recurrences of colorectal carcinoma were treated with PMC as the second-line chemotherapy, after 5-FU or its derivatives as the first-line chemotherapy. PMC was initiated with a 400 mg combination of uracil and tegafur daily and a 24-hour continuous intravenous infusion of 600 mg/m(2) 5-FU once weekly. The 5-FU dose was increased as the disease progressed.. Six (46%) of the 13 patients exhibited a partial response (PR) to PMC, based on the RECIST criteria. PR was achieved in 2 of 5, 2 of 5, and 2 of 3 patients undergoing oral administration of 5-FU derivatives, intravenous infusion of 5-FU/l-leucovorin and hepatic-artery infusion of 5-FU, respectively. The median survival time of the 13 patients was 17 months.Grade-2 toxicity was found only in 2 patients.. Because PMC is chronomodulating, it is an effective and safe treatment for recurrent colorectal carcinoma. PMC with a dose increase of 5-FU is recommended as a promising second-line regimen for unresectable colorectal carcinoma resistant to 5-FU.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chronotherapy; Colonic Neoplasms; Drug Administration Schedule; Drug Combinations; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Rectal Neoplasms; Survival Rate; Tegafur; Uracil

An 81-year-old man was admitted to our department due to acute ileus. He was diagnosed with sigmoid colon cancer with multiple metastatic lesions in the right lobe of the liver. Two weeks after insertion of an ileus tube, he underwent sigmoidectomy and permanent colostomy. The final diagnosis was stage IV sigmoid colon cancer with metastasis to the omentum. One month after the operation, adjuvant chemotherapy with oral administration of tegafur/uracil compound (UFT) and Leucovorin (LV), and drip venous infusion of irinotecan hydrochloride (CPT-11) was initiated (UFT 300 mg/day for 14 days, LV 75 mg/day for 14 days, CPT-11 90 mg/m(2) on the 1 st day, with 1 course consisting of 21 days). The levels of tumor markers, CA19-9 and CEA, and the size of metastases on CT were reduced remarkably after one and 4 courses of this therapy, respectively. Although the administration was temporarily discontinued due to low-grade nausea, we continued the treatment. Adjuvant chemotherapy with an oral administering agent is favorable for older patients with advanced colorectal cancer to reduce side effects and preserve the quality of life.

Topics: Adenocarcinoma; Administration, Oral; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colon, Sigmoid; Colostomy; Drug Administration Schedule; Drug Combinations; Humans; Infusions, Intra-Arterial; Irinotecan; Leucovorin; Liver Neoplasms; Male; Omentum; Peritoneal Neoplasms; Rectal Neoplasms; Remission Induction; Tegafur; Uracil

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Aorta, Thoracic; Bevacizumab; Camptothecin; Fluorouracil; Humans; Irinotecan; Leucovorin; Lung Neoplasms; Male; Middle Aged; Rectal Neoplasms; Thromboembolism; Tomography, X-Ray Computed

The clinical efficacy and safety of tegafur/uracil (UFT) plus oral Leucovorin (LV) regimen for advanced or metastatic colorectal cancer were studied retrospectively. From September 2003 to March 2005, 82 patients were treated with UFT (300 mg/m(2)/day)/LV (75 mg/day) at our institute. The objective overall response rate was 14. 8% (95% confidence interval, 5.3 to 24.3%) in 54 evaluable patients. The response rate was 33.3% for previously untreated patients and 5.5% for previously treated patients, respectively. Grade 3 or more severe adverse reactions such as diarrhea or liver function abnormalities were only 7.3%. In 28 previously untreated patients,the median survival was 25.8 months with 1-and 2-year survival rates of 88.0% and 60.5%, respectively. This retrospective study demonstrated the reproducible activity and safety of UFT/LV for advanced or metastatic colorectal cancer in clinical practice.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Diarrhea; Drug Administration Schedule; Drug Combinations; Female; Humans; Leucovorin; Male; Middle Aged; Nausea; Neoplasm Recurrence, Local; Rectal Neoplasms; Remission Induction; Retrospective Studies; Survival Rate; Tegafur; Uracil; Vomiting, Anticipatory

To examine retrospectively whether levels of epidermal growth factor receptor (EGFR) expression can predict tumor downstaging after preoperative chemoradiotherapy in patients with locally advanced rectal cancer.. A total of 183 patients with rectal cancer (cT3-T4 or N+) were enrolled in this study. Preoperative chemoradiotherapy consisted of 50.4 Gy of pelvic radiation with concurrent 5-fluorouracil and leucovorin bolus intravenous chemotherapy in 94 patients or oral capecitabine and leucovorin in 89 patients. EGFR expression in pretreatment paraffin-embedded tumor biopsy specimens was assessed by immunohistochemistry. EGFR expression was determined from the intensity and extent of staining. Tumor downstaging was defined as a reduction of at least one T-stage level.. Tumor downstaging occurred in 97 patients (53%), and the tumors showed a pathologic complete response in 27 patients (15%). Positive EGFR expression was observed in 140 (76%) of 183 patients. EGFR expression levels were low in 113 patients (62%) and high in 70 patients (38%). On logistic regression analysis, the significant predictive factor for increased tumor downstaging was a low level of EGFR expression and preoperative chemotherapy using oral capecitabine (odds ratio, 0.437; p = 0.012 vs. odds ratio, 3.235; p < 0.001, respectively).. A high level of EGFR expression may be a significant predictive molecular marker for decreased tumor downstaging after preoperative chemoradiotherapy in locally advanced rectal cancer.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Biomarkers, Tumor; Capecitabine; Combined Modality Therapy; Deoxycytidine; ErbB Receptors; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Radiotherapy Dosage; Rectal Neoplasms; Retrospective Studies

In Japan, cancer chemotherapy for advanced and recurrent colorectal cancer has not been adequately developed in comparison with the USA and Europe. However, the number of patients with advanced colorectal cancer has increased dramatically in this decade. Therefore, effective and feasible regimens against colorectal cancer are urgently needed. We designed a new regimen to evaluate the efficacy and feasibility of weekly low dose CPT-11 combined with 5-FU/l-LV therapy based on an RPMI regimen against advanced and recurrent colorectal cancer. Twenty patients were enrolled in this study. Weekly administration (CPT-11; 60 mg/m(2) div for 1st-line chemotherapy, 40 mg/m(2) div for 2nd-or 3rd-line chemotherapy, l-LV; 200 mg/m(2) div, 5-FU; 500 mg/m(2) iv, 3 consecutive weeks, 1-week break) was performed on an ambulatory basis. The treatment cycles were repeated every 4 weeks until disease progression and/or severe toxic events occurred. The overall response rate was 31.6% with 5.3% complete response and 26.3% partial response in addition to 42.1% with no changes beyond 3 months. These results suggested that the clinical benefit was shown in 73.7% of patients. Furthermore, median TTF (time to failure) of this regimen was 6.5 months and MST was 20.4 months, respectively. On the other hand, adverse events were restricted to grade 3 with 30.0% neutorocytopenia and 5.0% thrombocytopenia. Therefore, weekly low-dose CPT-11 combined with 5-FU/l-LV therapy seems to be extremely useful, with excellent anti-tumor effect and tolerable adverse reactions, for the treatment of advanced and recurrent colorectal cancer on an ambulatory basis.

Topics: Aged; Aged, 80 and over; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluorouracil; Hepatic Artery; Humans; Infusions, Intra-Arterial; Irinotecan; Leucovorin; Leukopenia; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Quality of Life; Rectal Neoplasms

We report a case of a 44-year-old male with advanced lower rectal cancer that showed a significant effect after preoperative chemoradiation therapy. Preoperative radiation and chemotherapy included whole pelvis irradiation (30 Gy in total), oral UFT (500 mg/day), and Leucovorin (75 mg/day) was administered daily for 4 weeks. Consequently, the patient underwent a total pelvic exenteration with lymph node dissection (D 3). Histopathological findings showed: invasion to peritoneum(Ai); stage IIIa with n(-); and histological grading, Grade 2. Preoperative chemoradiation therapy appears to be effective for locally advanced lower rectal cancer.

Topics: Adenocarcinoma; Administration, Oral; Adult; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Humans; Leucovorin; Male; Quality of Life; Radiotherapy Dosage; Rectal Neoplasms; Rectum; Tegafur; Uracil

A 53-year-old man, admitted for inguinal hernia, complained of body weight loss in a preoperative condition check. We examined the digestive tract and diagnosed stage IV advanced rectal carcinoma with multiple lung metastases. It caused ileus, so emergency colostomy was performed. After that his general condition recovered, and two cycles of neoadjuvant chemotherapy (NAC) by irinotecan combined with 5-fluorouracil and l-leucovorin (IFL) therapy were performed on an outpatient basis. Lung metastatic nodules disappeared. We established a diagnosis of down staging for stage IIIa, and performed a lower anterior resection with D 2 lymph node dissection to allow a curability-A resection. The pathological effect of NAC was Grade 2. Post-operatively, two cycles of IFL therapy were then performed. There has been no sign of recurrence, and no adverse effects by chemotherapy have been seen during this treatment. Thus, NAC by IFL therapy can be one of the useful treatment approaches for patients with advanced rectal cancer.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Colostomy; Drug Administration Schedule; Fluorouracil; Humans; Ileus; Irinotecan; Leucovorin; Lung Neoplasms; Lymph Node Excision; Male; Middle Aged; Neoplasm Staging; Rectal Neoplasms

Topics: Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Fluorouracil; Humans; Leucovorin; Rectal Neoplasms; Survival Rate

Topics: Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Fluorouracil; Guideline Adherence; Humans; Leucovorin; Rectal Neoplasms

We treated 3 cases of local pelvic recurrence due to a rectal cancer post operation by arterial infusion chemotherapy with 5-FU and levofolinate calcium and also by radiation therapy. The result of imaging analysis showed that a recurrent tumor was decreased effectively in 2 cases by chemo-radiation therapy. We confirmed the cancer pain and tumor bleeding were gone for all of the 3 cases. As for side effects of arterial infusion chemotherapy and radiation therapy, we confirmed a paralysis of the pelvic nerve in 1 case and dermatopathy in 1 case. This therapy seemed to be an effective treatment for elderly patients with inoperable cases.

Topics: Aged; Aged, 80 and over; Combined Modality Therapy; Fluorouracil; Humans; Infusions, Intra-Arterial; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Pelvic Neoplasms; Rectal Neoplasms

We report a patient with a case of advanced rectal cancer with unresectable liver metastasis, who received the combination of systemic chemotherapy of 5-FU/l-LV and external radiation therapy. He was alive for 21 months. He had been able to maintain a good quality of life without any complaints of the primary rectal tumor.

Topics: Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Quality of Life; Rectal Neoplasms

Recently, chemotherapy for the treatment of colorectal cancer was widely administered in Japan. Many various ideas were necessary to perform safe and efficient chemotherapy at our hospital. We experienced that even a patient with intellectual disability could have chemotherapy carry out smoothly in collaboration with a clinical pathway and visiting nursing care. The patient was a 63-year-old man who underwent low anterior resection of the rectum for advanced rectal cancer on April 2004. Multiple liver metastases had appeared in November 2004. Chemotherapy was administered because of the liver metastases. However, it was difficult to manage the side effect of the chemotherapy and we could not get cooperation from his family. A visiting nursing care was employed in cooperation with outpatient nursing for managing of the side effect. IFL regimen was carried out using a clinical pathway. The response became PD after 5 courses of an IFL regimen. The regimen was changed to FOLFOX4 on April 2005. No adverse events were seen beyond grade 2 during 10 courses of FOLFOX4 regimen.

Topics: Ambulatory Care; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Community Health Nursing; Cooperative Behavior; Critical Pathways; Drug Administration Schedule; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Rectal Neoplasms

Neoadjuvant chemoradiation treatment (CRT) has resulted in significant tumor downstaging and improved local disease control for distal rectal cancer. The purpose of the present study was to determine the correlation between final stage and survival in these patients regardless of initial disease stage. Two hundred sixty patients with distal (0-7 cm from anal verge) rectal adenocarcinoma considered resectable were treated by neoadjuvant CRT with 5-FU and leucovorin plus 5040 cGy. Patients with incomplete clinical response 8 weeks after CRT completion were treated by radical surgical resection. Patients with complete clinical response were managed by observation alone. Overall survival and disease-free survival were compared according to Kaplan-Meier curves and log-rank tests according to final stage. Seventy-one patients (28%) showed complete clinical response (clinical stage 0). One hundred sixty-nine patients showed incomplete clinical response and were treated with surgery. In 22 of these patients (9%), pathologic examination revealed pT0 N0 M0 (stage p0), 59 patients (22%) had stage I, 68 patients (26%) had stage II, and 40 patients (15%) had stage III disease. Overall survival rates were significantly higher in stage c0 (P=0.01) compared with stage p0. Disease-free survival rate showed better results in stage c0, but the results were not significant. Five-year overall and disease-free survival rates were 97.7% and 84% (stage 0); 94% and 74% (stage I); 83% and 50% (stage II); and 56% and 28% (stage III), respectively. Cancer-related overall and disease-free survival may be correlated to final pathologic staging following neoadjuvant CRT for distal rectal cancer. Also, stage 0 is significantly associated with improved outcome.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Rectal Neoplasms; Remission Induction

To evaluate the efficacy and toxicity of pre-operative radiotherapy (RT) combined with oral tegafur-uracil (UFUR) plus leucovorin (LV) in rectal cancer.. Sixty-five patients with rectal adenocarcinoma (clinical staged T2-4N0-2M0) received pelvic RT of 45 Gy in 20 fractions over 28 days. Concurrent chemotherapy consisted of UFUR (200 mg/m(2)/day) and LV (45 mg/day) on day 1-28. UFUR (250 mg/m(2)/day) and LV were continued on day 36-63. Surgery was performed on day 70.. Sixty-three patients completed the concurrent chemoradiotherapy (CCRT) and 56 received curative or palliative surgery. Among the 52 patients receiving curative resection, downstaging (DS) occurred in 39 (75%), pathological complete response in 13 (25%), and sphincter preservation was achieved in 16 of 29 (55%) with lower-seated tumors. With a median follow-up time of 33 months, local failure developed in 4 (8%) and distant metastases occurred in 7 (14%). The 3-year overall survival was 92% and disease-free survival 76%. For all 65 patients, grade 3-4 diarrhea developed in 6 (9%) and grade 3-4 leucopenia observed in 2 (3%).. Oral UFUR + LV administered with pre-operative RT are effective in tumor DS, pathological complete response, and sphincter preservation with tolerable toxicity in rectal cancer.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Disease-Free Survival; Drug Combinations; Female; Humans; Leucovorin; Male; Middle Aged; Palliative Care; Rectal Neoplasms; Survival Rate; Tegafur; Uracil

This study determined the efficacy and safety of a modified FOLFOX regimen that improved patient convenience without compromising oxaliplatin dose intensity. A total of 62 patients with previously untreated metastatic colorectal cancer were enrolled to receive, entirely as outpatients, 2-weekly cycles of oxaliplatin 100 mg m(-2) i.v. over 2 h, together with leucovorin 400 mg m(-2) over 2 h, 5-fluorouracil (5-FU) 400 mg m(-2), bolus, followed by a 46-h infusion of 5-FU at 2.4 g m(-2). Treatment was given until progression or unmanageable toxicity. In all, 61 patients received > or =one oxaliplatin dose and a median of 11 treatment cycles (range 1-20 cycles); 22 (36%) reported grade 3/4 neutropenia and 13 patients (21%) experienced grade 3 neurotoxicity; 16 patients (26%) discontinued treatment due to disease progression or death, 15 (25%) due to neurotoxicity and six (10%) due to haematological toxicity. Of the 56 eligible patients, complete or partial responses were observed in 29 or 52% (95% confidence interval 38-65%). Median progression-free survival was 8.2 months (7.1-9.9) and median overall survival was 18.7 months (14.0-23.4). In our experience, a modified schedule of FOLFOX improves convenience without compromising efficacy or toxicity.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Australia; Chemotherapy, Adjuvant; Colonic Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Hospitalization; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms; Survival Analysis

The objective was to determine the presence and frequency of micrometastasis in lymph nodes of patients with rectal cancer treated by preoperative chemoradiation followed by curative resection.. All 56 patients included were treated with 5-FU and leucovorin plus 5,040 cGy, followed by radical surgery and were diagnosed with stage II distal rectal adenocarcinoma after complete pathological examination (ypT3-4N0M0). Immunohistochemistry was assessed with cytokeratin monoclonal antibody AE1/AE3. Three 4-microm paraffin sections were obtained from each lymph node, cut at 50 microm apart from each other. The results were reviewed by two independent pathologists.. Mean number of lymph nodes was 9.6 per patient. Four patients (7%) and seven lymph nodes (1.35%) were positive for micrometastasis. Three patients had pT3 and one a pT4 tumor. One of the patients had positive micrometastasis and the presence of mucinous deposits. One other patient had mucinous deposits without any micrometastasis. All four patients are alive with no evidence of recurrent disease. Fourteen patients negative for micrometastasis had recurrent disease (25%), eight systemic (14.7%) and six locoregional (10.3%). There were two cancer-related deaths. The mean follow-up period was 39 months.. Patients with rectal cancer treated by preoperative chemoradiation showed a surprisingly low rate of micrometastasis detection (7%), even in high-risk patients (T3 and T4 tumors). Lymph node micrometastasis was not associated with decreased overall or disease-free survival. The identification of mucinous deposits on lymph nodes with no viable tumor cells may be direct evidence of lymph node downstaging. The downstaging effect of preoperative chemoradiation therapy may be significant in reducing even micrometastasis detection in low rectal cancer managed by this treatment strategy.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Digestive System Surgical Procedures; Female; Fluorouracil; Follow-Up Studies; Humans; Immunohistochemistry; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Radiotherapy, Adjuvant; Rectal Neoplasms; Treatment Outcome; Vitamin B Complex

The patient was a 43-year-old male with bilateral multiple liver metastases, who had undergone high anterior resection for rectal cancer (ss, n 0, P 0, H 3, M (-), stage IV). Hepatic arterial infusion (HAI) of low-dose CDDP (10 mg/body) and 5-FU (250 mg/body), 5 times a week, was ineffective for the liver metastases. Consequently, HAI of levofolinate (425 mg/body) and 5-FU (1,000 mg/body), once a week, was attempted. All metastatic liver tumors diminished apparently with calcification after the treatment (PR). Tumor marker (CA19-9 and CEA) levels decreased to less than one-tenth of the pretreatment levels and stabilized for approximately seven months. Mediastinal lymph node metastases, paraaortic lymph node metastases and tumor thrombus in the inferior vena cava were successfully treated with systemic chemotherapy using levofolinate and 5-FU and/or radiotherapy. Although the liver and lung metastases showed rapid growth, the patient died 2 years after the diagnosis of liver metastases. The liver metastases were well controlled for about 20 months. It is important to select interdisciplinary therapies according to the site of the metastases due to rectal cancer.

Topics: Adenocarcinoma; Adult; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Drug Administration Schedule; Fluorouracil; Hepatic Artery; Humans; Infusions, Intra-Arterial; Leucovorin; Liver Neoplasms; Lymphatic Metastasis; Male; Neoplastic Cells, Circulating; Radiotherapy Dosage; Rectal Neoplasms; Rectum; Vena Cava, Inferior

Toxicities and response are different when patients with advanced colorectal cancer were treated with standard FOLFOX6 regimen. Serum level of dihydropyrimidine dehydrogenase (DPD) relates to efficacy and toxicities of chemotherapy containing 5-fluorouracil (5-FU). This study was to explore relationship of DPD to serum concentration of 5-FU in colorectal cancer patients treated with FOLFOX6 regimen, and their correlation to treatment response and adverse events.. Serum level of DPD in 72 patients with colorectal cancer was detected by high-performance liquid chromatography (HPLC) before chemotherapy. Serum concentration of 5-FU at steady state was detected by HPLC after patients received FOLFOX6 regimen. Treatment response and adverse events in the patients were assessed.. Serum levels of DPD were normally distributed in 72 patients (ranged 1.55-5.94), while serum concentrations of 5-FU at steady state were not (ranged 141.1-1 741.9 microg/L). Serum level of DPD was negatively correlated with serum concentration of 5-FU (r=-0.460, P < 0.01). Occurrence of adverse events was lower when 5-FU concentration was less than 600 microg/L than when 5-FU concentration was more than 600 microg/L (P < 0.05). The mean serum concentration of 5-FU was significantly higher in patients with complete response and partial response than in patients with steady disease, and progressive disease (513.9 microg/L vs. 409.8 microg/L, and 259.3 microg/L, P < 0.05). Serum level of DPD was lower in patients suffered oral mucositis and diarrhea of grade II-IV than in patients suffered oral mucositis and diarrhea of grade 0-I (P=0.016, P=0.047). Serum level of DPD had no relation with treatment response of the patients (r=0.312, P=0.078).. DPD level and serum 5-FU concentration vary a lot among patients with colorectal cancer. DPD level negatively correlates with serum 5-FU concentration. Serum concentration of 5-FU correlates with treatment effect and toxicities.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Diarrhea; Dihydrouracil Dehydrogenase (NADP); Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Mucositis; Nausea; Organoplatinum Compounds; Rectal Neoplasms

This prospective study reports the results of a multimodality treatment protocol in patients with locally advanced rectal cancer and assesses outcome after curative vs non-curative surgery and in relation to primary advanced vs locally recurrent cancer.. Between 1991 and 2002, 122 patients completed the protocol. Fifty-eight had primary advanced and sixty-four had locally recurrent rectal cancer. Median follow up was 82 months (5-143).. A potentially curative resection was achieved in 59% of the patients with primary advanced and in 34% of patients with locally recurrent cancer. After curative resection, 53 and 59%, respectively, were free from recurrence during the observation time (median 82 months) and the overall 5-year survival was 34 and 40%. Overall 5-year survival in all patients with primary advanced cancer was 29 and 16% in all patients with locally recurrent rectal cancer.. Multimodality treatment may cure at least a third of patients with locally advanced rectal cancer provided a radical resection is performed. As the post-operative morbidity is high, an optimised patient selection for neo-adjuvant treatment and surgery is essential. However, palliative surgery may benefit the patient if local control is achieved. Future studies should focus on the problem of distant metastasis.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Prospective Studies; Rectal Neoplasms; Survival Analysis; Treatment Outcome

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials, Phase III as Topic; Combined Modality Therapy; Fluorouracil; Humans; Leucovorin; Neoadjuvant Therapy; Randomized Controlled Trials as Topic; Rectal Neoplasms

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Medical Oncology; Neoplasm Staging; Organoplatinum Compounds; Radiotherapy, Adjuvant; Rectal Neoplasms

The aim of this study was to evaluate the efficacy and toxicity of 5-fluorouracil (5-FU) and l-leucovorin (I-LV) in 50 patients with advanced or recurrent colorectal cancer in our institute. The dose of 5-FU was 600 mg/m2 and the dose of l-LV was 250 mg/m2. Objective response were 36.8% of patients who had administration of full-dose and 14.8% of patients who had the administration of reduced dose or prolonged interval. No significant difference was observed in clinical benefit rates between patients administrated in full-dose and patients in reduced dose or prolonged interval. Median survival time (MST) of patients in reduced dose or prolonged interval is longer than patients in full-dose. These data suggest that 5-FU/l-LV can be given in the outpatient and yields improved prognosis and minimal adverse reactions even in patients in reduced dose or prolonged interval.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Diarrhea; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Rectal Neoplasms; Retrospective Studies; Survival Rate

Intersphincteric resection of low rectal tumors is a surgical technique extending rectal resection into the intersphincteric space. This procedure is performed by a synchronous abdominoperineal approach with mesorectal excision and excision of the entire or part of the internal sphincter. This study was designed to evaluate the long-term results of this method focused on continence function and oncologic results.. From 1984 to 2000, a total of 121 patients were operated on. The patients were evaluated prospectively according to a detailed preoperative and postoperative program.. One hundred seventeen patients had rectal cancers, two had dysplastic villous adenomas, and two had carcinoid tumors. Cancers were staged according to the Dukes classification (Stage A in 41 percent, Stage B in 28 percent, and Stage C in 31 percent; median distance from the anal margin, 3 (range, 1-5) cm). Postoperative complications were: one death because of pulmonary embolism, 5.1 percent developed an anastomotic fistula, one patient had a fistula to the bladder requiring reoperation, one patient with ileus needed relaparotomy as well as one for intra-abdominal hemorrhage and a small-bowel fistula. One patient developed a fistula after closing the protective colostomy. Five patients developed late strictures of the coloanal anastomosis. After a median follow-up of 72.86 months, 5.3 percent of patients developed local recurrence. The continence status was satisfactory with 16 patients (13.7 percent) showing continence for solid stool only, and 1 patient (0.8 percent) showing episodes of incontinence. A transient problem was a high stool frequency after closure of the protective stoma.. Intersphincteric resection is a valuable procedure for sphincter-saving rectal surgery. We showed that this technique has satisfactory long-term results in functional and oncologic respects. An important prerequisite is a careful preoperative evaluation of local tumor spread with rectal magnetic resonance imaging excluding infiltration of the external sphincter.

Topics: Adenocarcinoma; Adenoma, Villous; Aged; Anal Canal; Antineoplastic Combined Chemotherapy Protocols; Carcinoid Tumor; Colectomy; Fecal Incontinence; Female; Fluorouracil; Humans; Leucovorin; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Staging; Prospective Studies; Recovery of Function; Rectal Neoplasms; Treatment Outcome

Pre-operative treatment with chemoradiotherapy (CRT) seems to improve local control and overall survival in patients with rectal cancer. The aims of the study were to analyse the impact on overall, disease free and cancer related survival of tumour response to pre-operative CRT and to analyse the influence of the degree of response on long-terms results.. Patients with a locally advanced rectal cancer, treated by pre-operative CRT were studied. A radical resection of the rectal tumour with mesorectal excision was performed within 6-8 weeks. Judged on the final TNM classification patients were considered responders when the tumour showed histologically a complete response, microscopic residual disease or a partial response. Non-responders were those in whom the extent of disease remained stable or progressed. Results Radical excision was performed in 103 patients, and a palliative resection in five. Forty-three patients underwent abdominoperineal resection and 65 anterior resection of the rectum. Seventy-one (65.7%) patients showed a response to CRT, while 37 (34.3%) did not. The overall local and distant recurrence rates were 6.8% and 21.3%. Tumour recurrence (P < 0.008) and disease free survival (P < 0.007) were significantly different in responders and nonresponders. Of the 71 responders, 16 had a pathological complete response, 27 had persisting microscopic disease and 28 had macroscopic residual disease. No differences in cancer specific outcome were observed in these groups.. Pathological response to pre-operative CRT is associated with improved tumour recurrence and disease-free survival rates. Any response to pre-operative CRT appears to improve outcomes as much as a complete response.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chi-Square Distribution; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Patient Selection; Rectal Neoplasms; Survival Rate; Treatment Outcome

To determine the prognostic significance of the nodal stage and number of nodes recovered in the surgical specimen after preoperative synchronous chemoradiation (SCRT) and surgery for locally advanced or unresectable rectal cancer.. One hundred and eighty-two consecutive patients with locally advanced or unresectable (T3/T4) rectal carcinomas were entered on a prospective database and treated in this department with preoperative chemoradiation, followed 6-12 weeks later by surgical resection. Most patients received chemotherapy in the form of low-dose folinic acid and 5-fluorouracil (5-FU) 350 mg/m2 via a 60-min infusion on days 1-5 and 29-33 of a course of pelvic radiotherapy delivered at a dose of 45 Gy in 25 fractions over 33 days to a planned volume. After resection, patients with a positive circumferential margin (< or = 1 mm), extranodal deposits or Dukes' C histology received adjuvant 5-FU-based-chemotherapy (n = 40).. After SCRT, 161 patients underwent resection. Twenty-one patients remained unresectable or refused an exenterative operation. Median follow-up is 36 months. Down-staging was achieved in most patients, with 19 having a complete pathological response (pT0). The median number of lymph nodes recovered for all patients was five (range 0-21). The 3-year survival rate for node-positive patients is 47%, for node-negative patients with less than three lymph nodes recovered is 62% and for node-negative patients with three or more lymph nodes recovered is 70%. Compared with node-positive patients, simple regression models revealed a reduced hazard ratio (HR) of 0.72 (0.36-1.43) for node-negative patients with less than three nodes recovered and 0.48 (0.26-0.89) for node-negative patients with three or more lymph nodes recovered. In a multivariate model, including nodal status, excision status, age and sex only positive excision margins significantly predicted a poor outcome: HR = 3.05 (1.55-5.97).. The number of nodes found after preoperative chemoradiation is a significant prognostic factor by univariate analysis. In this study, patients with node-negative histology, and at least three nodes recovered, had better long-term survival than patients in whom two or less nodes were recovered or with positive nodes. This effect was attenuated by the inclusion of excision status in multivariate models.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Preoperative Care; Prognosis; Prospective Studies; Rectal Neoplasms; Reproducibility of Results; Risk Factors; Survival Rate; Treatment Outcome

This study set out to determine the impact of a positive circumferential resection margin (CRM) (R1-R2) and pathologic downstaging on local recurrence and survival in patients with borderline resectable or unresectable rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy (CRT).. A total of 150 patients with locally advanced rectal cancer were treated with long-course neoadjuvant CRT using low-dose folinic acid and 5-fluorouracil. CRT was followed 6-12 weeks later by surgical excision. The CRM rate and incidence, site, and pattern of local and systemic recurrences were recorded. The median follow-up was 25 months.. The overall median survival was 37 months, with a 5-year overall survival rate of 34%. Of the 150 patients, 122 underwent curative resection; 12% had a complete pathologic response, and downstaging to pT1-T2 occurred in an additional 16%. A negative CRM (R0) was achieved in 65% overall (98 of 150). Local recurrence occurred in 10% of those with R0 resection and 62% of those with R1-R2 resections. Distant metastases occurred in 29% of those with R0 resections and 75% of those with R1-R2 resections. The 3-year disease-free and 3-year overall survival rate was 9% and 25% and 52% and 64%, respectively, for patients with and without a histologically positive CRM.. After 5-fluorouracil-based CRT, a positive CRM predicted for a high risk of subsequent local recurrence and a 3-year disease-free survival rate of only 9%. For this reason, the CRM should be considered a major prognostic factor and should be validated in future trials as an early alternative clinical endpoint.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Antimetabolites, Antineoplastic; Combined Modality Therapy; Disease-Free Survival; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Mitomycin; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasm, Residual; Radiotherapy Dosage; Rectal Neoplasms; Survival Rate

The aim of this study was to evaluate the efficacy of tegafur/uracil (UFT) and oral Leucovorin(UZEL) in patients with advanced or recurrent colorectal cancer. Eight patients were treated with UFT/UZEL therapy as a first-line chemotherapy. UFT(300 mg/m(2)/day) and UZEL (75 mg/body/day) were administered orally for 28 consecutive days followed by a 7-day rest period, and this schedule was repeated every 5 weeks. The mean of treatment courses given to the patients was 7.6. Tumor response was evaluated in 7 patients who had assessable lesions, and the response rate was 86% (6 PR and 1 NC). Adverse reactions of grade 3 were observed in 2 patients (25%), but toxicity did not cause a discontinuance of treatment in any case. The UFT/UZEL therapy was considered to be a promising regimen for advanced or recurrent colorectal cancer from a standpoint of effect, safety and QOL of patients.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Drug Administration Schedule; Female; Humans; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Quality of Life; Rectal Neoplasms; Tegafur; Uracil

Fifty-one-year-old male visited our hospital suffering from anal pain and subileus. Further examination revealed that advanced rectal cancer which invaded to presacral space (Ai, N 0, P 0, H 0, M(-), stage IIIa) caused such symptom. We administered neo-adjuvant chemoradiotherapy for fear of non curative resection of the rectum. The regimen was once weekly administration of intravenous CPT-11 40 mg, plus daily oral administration of UFT-E 600 mg/day and Uzel 75 mg/day for 4 weeks. In addition we underwent radiation 2.4 Gy/day and intravenous low-dose cisplatin (CDDP) 5 mg/day, 5 days/week for 3 weeks. Four weeks after the first administration, a partial response was confirmed on CT, and so we carried out an abdominoperineal resection. The postoperative course is almost uneventful without a little perineal infection. The specimen revealed that no malignant lesion remained, which changed to necrotic tissue. The side effects were not so severe. For example, diarrhea, nausea, and mucosal dysfunction were each less than grade 2, and there was much tolerate for renal, liver, and bone marrow function. This combination chemoradiotherapy is considered to be effective for locally advanced rectal cancer.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Colostomy; Drug Administration Schedule; Drug Combinations; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Preoperative Care; Rectal Neoplasms; Rectum; Remission Induction; Tegafur; Uracil

Topics: Adult; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colonoscopy; Colorectal Neoplasms; Diagnosis, Differential; Female; Fluorouracil; Humans; Leucovorin; Male; Mass Screening; Middle Aged; Neoplasm Staging; Occult Blood; Organoplatinum Compounds; Oxaliplatin; Prognosis; Radiography, Abdominal; Rectal Neoplasms; Tomography, X-Ray Computed; Vitamin B Complex

Intra-arterial infusion chemotherapy via the internal iliac artery was performed in 5 patients with locally advanced rectal cancer or recurrent rectal cancer. Arterial infusion chemotherapy was conducted into the internal iliac artery via bilateral femoral artery following a blood flow change with a coil. 5 FU 500 mg and l-leucovorin 125 mg/m2 were injected weekly. An average time of injections or its duration was 40 (17-74) times or 12.8 (5-23) months, respectively. Disappearance or improvement of symptoms was observed in 4 cases. A decrease of tumor size observed by CT was in 2 cases and a decrease of blood CEA level was in 3 cases. As for the complication of arterial infusion chemotherapy, dermatopathy was found in all of the cases, and sensory disturbance of lower extremities was in 3 cases, infection was in 2 cases and catheter obstruction was in 2 cases. A decrease of dosage or abundance of continuation was done during the course due to complications. Two patients with primary cancer died 1-3 years after the treatment, and 2 patients with recurrence died 7 months to 1 year after the treatment. One patient with primary cancer is continuing the treatment for the last 2 years though multiple metastatic diseases have been confirmed.

Topics: Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Iliac Artery; Infusions, Intra-Arterial; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Rectal Neoplasms; Treatment Outcome

We present a patient with colon carcinoma metastatic to the thyroid. Review of the literature reveals only a few reports of metastatic colorectal carcinoma to the thyroid. Metastatic tumors of the thyroid are no longer considered rare. Unfortunately, they often remain undetected because only a small minority of patients present with a mass lesion or enlargement of the gland. This is further evidenced by the fact that most reports come from autopsy series. Establishing this diagnosis is important because metastatic deposits in the thyroid can sometimes cause respiratory compromise as well as thyrotoxicosis.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Camptothecin; Colectomy; Female; Fluorodeoxyglucose F18; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Middle Aged; Positron-Emission Tomography; Radiopharmaceuticals; Radiotherapy; Rectal Neoplasms; Thyroid Neoplasms; Thyroidectomy; Treatment Outcome

Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Chemoradiotherapy; Colonic Neoplasms; Fluorouracil; Humans; Leucovorin; Organoplatinum Compounds; Practice Guidelines as Topic; Radiotherapy, Adjuvant; Rectal Neoplasms

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Cetuximab; Colonic Neoplasms; Fluorouracil; Humans; Leucovorin; Organoplatinum Compounds; Rectal Neoplasms

In stage II (T3-4N0) and III (TxN1-2) rectal cancer, adjuvant radiochemotherapy improves overall survival and decreases the rate of local failure compared to only surgical therapy and is regarded as standard for patients with carcinoma of the lower and intermediate rectum. (Preoperative) radiotherapy also decreases the local failure rate following total mesorectal excision. Postoperative radiotherapy has no proven influence on distant metastasis rates or on overall survival. In adjuvant therapy, continuous infusion of 5-flourouracil compared to bolus application increases long-term survival. However, additional administration of leucovorin or levamisole results in increased toxicity and not improved survival. Results of randomized trials of adjuvant therapy with new drugs such as capecitabine, UFT, irinotecan, or oxaliplatin are not yet available. These drugs should not be used outside clinical trials. Elderly patients benefit from adjuvant therapy to the same extent as younger patients and should receive adjuvant radiochemotherapy, if no contraindication exists.

Topics: Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Camptothecin; Chemotherapy, Adjuvant; Clinical Trials as Topic; Combined Modality Therapy; Fluorouracil; Humans; Irinotecan; Leucovorin; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Organoplatinum Compounds; Oxaliplatin; Radiotherapy Dosage; Randomized Controlled Trials as Topic; Rectal Neoplasms; Time Factors

The patient was a 58-year-old female who had a cancer of the rectum with multiple lymph node metastases including paraaortic lymph nodes and Virchow lymph nodes. Abdominoperineal resection was performed palliatively. After the operation, weekly bolus of 5-fluorouracil combined with levofolinate was carried out. After 2 courses of chemotherapy, metastases of paraaortic lymph nodes and Virchow lymph nodes completely disappeared upon CT examination. Chemotherapy has continued for 14 months, and she is well and has maintained a complete response for more than 1 year. This case suggests that this combination chemotherapy of LV/5-FU, admitted in Japan, is effective against advanced colorectal cancer.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Rectal Neoplasms; Remission Induction

Topics: Administration, Oral; Anticonvulsants; Antimetabolites, Antineoplastic; Carcinoma; Drug Interactions; Epilepsy; Humans; Leucovorin; Male; Middle Aged; Phenytoin; Rectal Neoplasms; Tegafur

Preoperative adjuvant radiation combined with chemotherapy is a recent development in the management of patients with rectal cancer invading perirectal tissue and regional lymph nodes. This study was performed to assess the impact of preoperative adjuvant therapy in patients judged by endorectal ultrasound to have extramural invasion of rectal cancer and/or regional lymph node involvement on tumor regression in bowel wall T and lymph nodes N. The predictive value of ultrasound in staging wall penetration and lymph node involvement after preoperative adjuvant therapy was also assessed.. Fifty-one patients were selected by ultrasound to have preoperative irradiation (40-50 Gy over 5-6 weeks). In 29 patients this was combined with 5-fluorouracil chemotherapy. Assessments of ultrasound were compared with pathologic findings in the resected specimen in all patients.. Partial downstaging was seen in 37 (72.5%) patients with wall invasion T and in five (9.8%) of 51 patients with lymph node involvement N. Complete downstaging was achieved in one (2.0%) patient with wall invasion T and in 20 (39.2%) of 51 patients with lymph node involvement N. Positive predictive values of ultrasound after irradiation were 47 (92.2%) and 45 (82.2%) for wall penetration and lymph node status, respectively. Negative predictive values of ultrasound after irradiation were rare 3.9% and 5.9%, respectively.. In the majority of patients with rectal cancer invading perirectal tissues or lymph nodes, lesions downstages by preoperative chemo radiotherapy. Endorectal ultrasound examination before and after chemo radiotherapy for rectal cancer is one of the most recommended in staging rectal cancer.

Topics: Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Carcinoma in Situ; Chemotherapy, Adjuvant; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Predictive Value of Tests; Preoperative Care; Radiotherapy Dosage; Radiotherapy, Adjuvant; Rectal Neoplasms; Rectum; Time Factors; Treatment Outcome; Ultrasonography

Colon and rectal cancer are in France a challenging problem in public health, reaching the second place in cancer related deaths. Surgery is still the key of curative treatment. Crude survival increased from 33% to 55% during twenty years. Colonoscopy is the referent exam for positive diagnosis. In rectal cancer, endorectal ultrasound and MRI have optimised local staging. The quality of general staging is important since it could change therapeutic strategy. Spiral CT scan is now probably superior to conventional ultrasound in the detection of liver metastases. Laparotomy is still the standard surgical approach. Main prospective studies in the evaluation of laparoscopic approach are still ongoing. Rectal resection for cancer is today a standardised procedure: total mesorectal excision (TME) should be done for rectal tumours below peritoneal reflection; TME decreases both the risk of local recurrence and the frequency of urogenital sequelae. The quality of surgical resection for colorectal cancer should always be checked and particularly, the number of lymph nodes, the longitudinal and lateral margins for rectal cancer, and resection for fixed tumours. Adjuvant chemotherapy with 5 fluorouracil and folinic acid is a standard for UICC stage III patients, but with a clearer benefit for colon tumours. Preoperative irradiation for T3-T4 rectal tumours is an European standard, providing a better local control; irradiation could also improved survival. In the oncoming years, surgeon and hospital specialization will probably be the main factor of progress in the management of colorectal cancer in France.

Topics: Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Colon; Colonoscopy; Colorectal Neoplasms; Drug Therapy, Combination; Endosonography; Fluorouracil; Humans; Laparoscopy; Laparotomy; Leucovorin; Liver Neoplasms; Magnetic Resonance Imaging; Neoplasm Recurrence, Local; Neoplasm Staging; Preoperative Care; Prospective Studies; Radiotherapy, Adjuvant; Rectal Neoplasms; Rectum; Risk Factors; Tomography, Spiral Computed

We treated 2 patients with colorectal cancer accompanied by liver metastasis who showed favorable response to combined treatment with fluorouracil and l-Leucovorin. Case 1 was a 40-year-old man with rectal carcinoma (moderately differentiated adenocarcinoma; se, n1, p1, H0, stage IV). He underwent low anterior resection of the rectum and postoperatively showed an increase peritoneal dissemination and liver metastasis. The patient was given 600 mg/m2 fluorouracil and 250 mg/m2 l-Leucovorin concomitantly for 7 courses. At course 3, the liver metastasis showed partial response and, during the 18 months after the 7th course, his peritoneal dissemination and other lesions were well controlled. As of 30 months post-treatment the patient was alive. Case 2 was a 60-year-old man with rectal carcinoma (well differentiated adenocarcinoma; ss, n1, p0, H1, stage IV). He underwent low anterior resection and postoperatively was given 3 courses of fluorouracil and l-Leucovorin. At course 2, he showed complete response, and, at present 8 months after the 2 courses, the patient continues to show complete response. Adverse drug reactions in both patients were controlled on an outpatient basis. While in the past liver metastasis has been treated by hepatic arterial infusion chemotherapy, a combination therapy with fluorouracil and l-Leucovorin can be used on an outpatient basis and results in a favorable response. This suggests that this combination therapy has clinical significance.

Topics: Adenocarcinoma; Adult; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Fluorouracil; Hepatic Artery; Humans; Infusions, Intra-Arterial; Leucovorin; Liver Neoplasms; Male; Middle Aged; Peritoneal Neoplasms; Rectal Neoplasms

Oxaliplatin is a third-generation platinum analog that is used mainly to treat advanced colorectal cancer. The reported incidence of hypersensitivity reactions to oxaliplatin, especially after multiple cycles of therapy, is less than 1%. We report a patient with metastatic colon cancer who developed a hypersensitivity reaction to oxaliplatin during the sixth cycle of combination chemotherapy with oxaliplatin, high-dose 5-fluorouracil and leucovorin. The same reaction occurred again after re-exposure to oxaliplatin 2 weeks later even with prophylactic administration of steroids and H1 antihistamines. After failing third-line treatment with oral tegafur-uracil, we desensitized the patient by using a fixed-rate 24-h continuous infusion of dilute oxaliplatin (0.15 mg/ml), in addition to steroids and H1 antihistamines. He had no hypersensitivity reaction during or after that infusion or when the same concentration was infused in the same way 2 weeks later. Because his condition subsequently deteriorated and the cancer progressed, no further oxaliplatin was given. Our experience does demonstrate, however, that a fixed-rate 24-h continuous infusion of oxaliplatin in a low concentration may prevent a hypersensitivity reaction in a previously sensitized patient.

Topics: Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Desensitization, Immunologic; Dexamethasone; Diphenhydramine; Drug Administration Schedule; Drug Hypersensitivity; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Liver Neoplasms; Male; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms; Taiwan; Time Factors

For synchronous liver metastases from rectal cancer, after extirpation of the primary lesion, a transcatheter arterial embolization was postoperatively performed 3 times at 6-month intervals. Metastatic lesions in S1 and S8 resulted in progressive disease at 8 and 13 months postoperatively, and simultaneous sharp elevation of both CEA and CA19-9 levels. Therapy was then changed to hepatic arterial infusion (HAI) chemotherapy combined with 5-fluorouracil and l-leucovorin (17 months postoperatively). S1 and S8 demonstrated CR and PR, respectively, 8 months after initiation of HAI. Correspondingly, both CEA and CA19-9 levels decreased dramatically, and have thereafter remained stable to date without marked elevation 36 months after the start of HAI. These findings suggest that our regimen for HAI chemotherapy may effectively control liver metastases and restrain progression over the long-term, that is, establish "tumor dormancy" as proposed in recent years. Moreover, CEA and CA19-9 played important roles as surrogate markers that reflect the response to metastatic tumors.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Drug Administration Schedule; Fluorouracil; Hepatic Artery; Humans; Infusion Pumps, Implantable; Infusions, Intra-Arterial; Leucovorin; Liver Neoplasms; Male; Rectal Neoplasms

Report overall long-term results of stage 0 rectal cancer following neoadjuvant chemoradiation and compare long-term results between operative and nonoperative treatment.. Two-hundred sixty-five patients with distal rectal adenocarcinoma considered resectable were treated by neoadjuvant chemoradiation (CRT) with 5-FU, Leucovorin and 5040 cGy. Patients with incomplete clinical response were referred to radical surgical resection. Patients with incomplete clinical response treated by surgery resulting in stage p0 were compared to patients with complete clinical response treated by nonoperative treatment. Statistical analysis was performed using chi2, Student t test and Kaplan-Meier curves.. Overall and disease-free 10-year survival rates were 97.7% and 84%. In 71 patients (26.8%) complete clinical response was observed following CRT (Observation group). Twenty-two patients (8.3%) showed incomplete clinical response and pT0N0M0 resected specimens (Resection group). There were no differences between patient's demographics and tumor's characteristics between groups. In the Resection group, 9 definitive colostomies and 7 diverting temporary ileostomies were performed. Mean follow-up was 57.3 months in Observation Group and 48 months in Resection Group. There were 3 systemic recurrences in each group and 2 endorectal recurrences in Observation Group. Two patients in the Resection group died of the disease. Five-year overall and disease-free survival rates were 88% and 83%, respectively, in Resection Group and 100% and 92% in Observation Group.. Stage 0 rectal cancer disease is associated with excellent long-term results irrespective of treatment strategy. Surgical resection may not lead to improved outcome in this situation and may be associated with high rates of temporary or definitive stoma construction and unnecessary morbidity and mortality rates.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Agents; Colostomy; Disease-Free Survival; Female; Fluorouracil; Follow-Up Studies; Humans; Ileostomy; Leucovorin; Longitudinal Studies; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Radiotherapy Dosage; Rectal Neoplasms; Remission Induction; Survival Rate; Treatment Outcome

We have experienced successful treatment of a multiple hepatic metastasis of rectal cancer with combination chemotherapy. The patient is a 57-year-old male with bowel obstruction accompanied by rectal cancer (SE, N3, P1, H3, M (-) stage IV) who underwent a Hartmann operation with D3 lymph node dissection on July 6, 2000. The histopathological findings revealed a well-differentiated adenocarcinoma (se, INFbeta, n3, ly2, v2, p1). From the 11th postoperative day, combination chemotherapy using 5-FU 750 mg/day and LV 300 mg/day was performed once a week. When he underwent 5 combination chemotherapy treatments, adverse effects of grade 3 occurred, and the serum CEA level rose rapidly. We changed his regimen at that time. He underwent 2 courses of combination chemotherapy with 5-FU 500 mg/day and CDDP 10 mg/day for 5 days. Additional courses of combination chemotherapy with 5-FU 500 mg/day, LV 25 mg/day and CDDP 10 mg/day were performed weekly in the outpatient department. The treatment was effective, and a complete response (CR) was noted 4 months after the chemotherapy. The same combination chemotherapy was performed biweekly for one year after CR. The patient has been receiving a subsequent single administration of UFT and has remained in remission for 3 years and 7 months after surgery.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Administration Schedule; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Peritoneal Neoplasms; Rectal Neoplasms; Remission Induction

A 55-year-old man underwent a rectal amputation for rectal cancer in 1994. As the tumor marker was elevated in 2002, we performed an abdominal CT scan and detected local and multiple liver recurrences. We treated the patient with intra-arterial infusion of 5-FU/LV via the internal iliac artery and the hepatic artery. The chemotherapy was performed on a weekly basis; it consisted of 5-FU (500 mg/body), administered for 5 hours to bilateral reservoirs through an infusion pump and l-leucovorin (400 mg/body), administered intravenously for 2 hours. After 18 administrations of this regimen during a hospital stay and after a discharge from the hospital as an outpatient, the multiple liver metastases that were observed have disappeared. Further, the local recurrences showed a partial reduction in tumor size with a decrease in perineal pain. Subsequently, the patient did not require further doses of morphine. He exhibited no severe side effects except for grade 1 nausea, and his QOL was also good. Therefore, local intra-arterial infusion chemotherapy with 5-FU/LV appears to have been effective for rectal cancer recurrences.

Topics: Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Hepatic Artery; Humans; Iliac Artery; Infusions, Intra-Arterial; Infusions, Intravenous; Leucovorin; Liver Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Pelvic Neoplasms; Postoperative Complications; Rectal Neoplasms

The efficacy and toxicity of 5-FU was various in different patients. It was reported that they were correlated to the activity of dihydropyrimidine dehydrogenase (DPD). This study is to measure DPD activity in blood and to analyze the relationship among DPD activity, the toxicity of 5-FU based adjuvant chemotherapy and the 5-FU plasma concentration in colorectal cancer patients.. 30 colorectal cancer patients were enrolled into the study to receive adjuvant chemotherapy 2 weeks after cured resection. The regimen was 5-FU 425 mg/m(2) plus CF 60 mg/m(2) continuous infused for 2 hours, daily for 5 days. The concentration of endogenous uracil (U) and dihydrouracil (UH(2)) were assayed by high performance liquid chromatography (HPLC). The UH2-U ratio in plasma was used to represent DPD activity in blood. The plasma samples were collected before chemotherapy in all patients to detect the DPD activity in blood, and after 5-FU infusion at day 1 and day 5 to measure 5-FU plasma concentration. The relationship among the DPD activity in blood, the toxicity of chemotherapy and the plasma concentration of 5-FU in all patients were analyzed.. 30 colorectal cancer patients have received adjuvant chemotherapy. The DPD activity in the blood of 30 colorectal cancer patients before chemotherapy was 4.09+/-1.21 (2.14-6.7), showed a trend of normal distribution. The 5-FU plasma concentration after 5-FU infusion was (2 079.12+/-621.41) microg/L (1 200.10-3 554.80 microg/L) at the first day, and (2 197.64+/-606.78) microg/L at the fifth day (1 259.00-3 441.03 microg/L). There was a negative relationship between the DPD activity in blood and the 5-FU plasma concentration at day 1 (r=-0.773, P=0.00), and day 5 after 5-FU infusion(r = -0.833, P = 0.00). No significant difference between the 5-FU plasma concentration of day 1 and day 5 was found (P=0.458). The 5-Fu associated toxicities had a negative relationship with DPD activity in blood, and had a positive relationship with 5-FU plasma concentration (P< 0.05).. The results indicated that the DPD activity in blood can be used to predict the toxicity and the 5-FU plasma concentration in patients with 5-FU based chemotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colonic Neoplasms; Dihydrouracil Dehydrogenase (NADP); Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Rectal Neoplasms

The aim of this study was to evaluate factors associated with pathologic tumor response following pre-operative chemoradiation therapy, and the prognostic impact of pathologic response on overall and disease-free survival.. Between 1994 and 2002, 132 patients underwent chemoradiation therapy followed by surgery for middle to lower rectal cancer. After excluding 26 cases (metastatic cancer, n = 13; nonradical surgery, n = 6; local excision procedure, n = 4; non-5-fluorouracil-based chemotherapy, n = 2; incomplete data on preoperative chemoradiation therapy regimen used, n = 1), the remaining 106 patients were included in the study. Variables considered were the following: age, gender, tumor location, pretreatment T and N stage, modality of 5-fluorouracil administration, total radiotherapy dose delivered, chemoradiation therapy regimen used (Regimen A: chemotherapy (bolus of 5-fluorouracil and leucovorin, days 1-5 and 29-33) + radiotherapy (45 Gy/25 F/1.8 Gy/F); Regimen B: chemotherapy (5-fluorouracil continuous venous infusion +/- weekly bolus of carboplatin or oxaliplatin) + radiotherapy (50.4 Gy/28 F/1.8 Gy/F)), time interval between completion of chemoradiation therapy and surgery, postoperative chemotherapy administration, surgical procedures, pT, pN, and pTNM stage, and response to chemoradiation therapy defined as tumor regression grade, scored from 1 (no tumor on surgical specimen) to 5 (absence of regressive changes). Statistical analysis was performed by means of logistic regression analysis (Cox's model for overall and disease-free survival).. Median age of the 106 patients was 60 (range, 31-79) years and the male:female ratio, 66:40. Median distance of tumor from the anal verge was 6 (range, 1-11) cm. Pretreatment TNM stage, available in 104 patients, was cT3T4N0, n = 41; cT2N1, n = 9; cT3N1, n = 39; and cT4N1, n = 17. The median radiotherapy dose delivered was 50.4 (range, 40-56) Gy; 58 patients received 5-fluorouracil by continuous venous infusion, and carboplatin with oxaliplatin was added to the chemotherapy schedule in 71 cases. Patients were given Regimen A in 47 cases and Regimen B in 59. The median interval between chemoradiation therapy and surgery was 42.5 (range, 19-136) days, and 94 patients underwent a sphincter-saving procedure. Tumor regression grade, available in 104 cases, was 1, n = 19; 2, n = 18; 3, n = 15; 4, n = 13; and 5, n = 39. At a median follow-up of 42 (range, 1-110) months, 11 patients had died, and 95 were alive. None of the patients had local recurrences, but 13 had distant recurrences. At logistic regression analysis, the chemoradiation therapy regimen used was the only independent predictor of tumor response following preoperative chemoradiation therapy (odds ratio = 0.29, 95% confidence interval = 0.13-0.67, P = 0.003). At Cox's regression analysis, pretreatment T stage was the only independent prognostic factor for both disease-free survival (relative risk = 7.13, 95% confidence interval = 2.3-21.8, P = 0.001) and overall survival (relative risk = 4.83, 95% confidence interval = 1.1-19.9, P = 0.029).. Tumor response following preoperative chemoradiation therapy is mainly related to the preoperative regimen used. For patients receiving preoperative chemoradiation therapy, pretreatment T stage, but not tumor response to preoperative chemoradiation therapy, is prognostic for outcome (both disease-free and overall survival).

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Chi-Square Distribution; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Logistic Models; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Prognosis; Proportional Hazards Models; Radiotherapy Dosage; Rectal Neoplasms; Retrospective Studies; Survival Analysis; Treatment Outcome

Irinotecan (CPT11) has established activity against advanced colorectal cancer without cross-resistance with 5-fluorouracil + leucovorin-based therapy. We conducted this pilot study to evaluate the efficacy and tolerance of combination treatment with irinotecan and 5-fluorouracil (5-FU) for patients in whom combination treatment with oxaliplatin with 5-FU + leucovorin has failed.. Patients were enrolled in this study after oxaliplatin treatment had failed. The treatment protocol consisted of CPT11 (180 mg/m(2) for 90 min) on day 1 and a 2 h infusion of 200 mg/m(2) leucovorin followed by 400 mg/m(2) 5-FU as an intravenous bolus injection plus a 22 h continuous infusion of 600 mg/m(2) 5-FU. This regimen was repeated for two consecutive days every 2 weeks.. A total of 18 patients were eligible for this study and in total 144 cycles of therapy (median eight cycles) were given to these patients. Four patients (22.2%; 95% CI: 8-36.4%) achieved an objective response of partial remission (PR) and an additional seven obtained stable disease (SD) status or minor response. The median duration of response was 8 months and 14 patients were alive at the end of the study. Hematological toxicity (neutropenia) was the most common serious side effect (29.2%), followed by gastrointestinal effects (diarrhea, 28.5%). Grade II-III diarrhea was experienced for at least one cycle by each patient.. The results of treatment for patients after oxaliplatin failure are encouraging and this treatment protocol is also well tolerated by previously heavily treated patients.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Drug Administration Schedule; Fluorouracil; Humans; Irinotecan; Leucovorin; Leukopenia; Middle Aged; Nausea; Pilot Projects; Rectal Neoplasms; Salvage Therapy; Survival Analysis; Treatment Outcome; Vomiting, Anticipatory

To evaluate the role of strength and endurance training for the muscular, cardiac, respiratory, and immune systems and the quality of life (QOL) during intrahepatic chemotherapy (folinic acid, 5-fluorouracil).. Single case.. Teaching hospital in Germany.. An elderly athlete with liver metastasis after resection of a carcinoma of the rectum (pT3, N0, M-liver, G2).. Strength and endurance training during chemotherapy.. During the intervals between training cycles (14d), beginning in postoperative week 6, a strength and endurance training regimen was performed twice weekly for 13 weeks, with an intensity of 40% to 60% of the maximum postoperative individual power and endurance. Before and after chemotherapy, we checked echocardiograms, resting and exercise electrocardiograms, lung function, natural killer (NK) cells, and the Gastrointestinal Quality of Life Index (GIQLI) scores.. The increase in strength was between 0% and 144%. The improvement in endurance expressed by reduction of heart rate and lactate concentration was 10% and 21.5%, respectively. Lung function also improved with regard to forced expiratory volume in 1 second (12.9%), forced vital capacity (11.3%), and inspiratory vital capacity (11.4%). The relative count of the NK cells increased to 27.2%. An improvement in the GIQLI was observed from 109 points (pathologic) to 129 points.. Strength and endurance training was associated with an increase of physical strength and endurance with positive influence on illness-related QOL. Postoperative physical exercise during regional chemotherapy is beneficial.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Exercise Therapy; Fluorouracil; Forced Expiratory Volume; Heart Rate; Humans; Infusions, Intralesional; Killer Cells, Natural; Leucovorin; Liver Neoplasms; Lymphocyte Count; Male; Middle Aged; Palliative Care; Physical Endurance; Physical Fitness; Quality of Life; Rectal Neoplasms; Vital Capacity; Weight Lifting

Topics: Adult; Aged; Anticoagulants; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Drug Therapy, Combination; Female; Fluorouracil; Humans; Incidence; International Normalized Ratio; Leucovorin; Liver Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Prothrombin Time; Rectal Neoplasms; Warfarin

The purpose of this study was to determine whether a complete pathologic response after neoadjuvant therapy in rectal cancer patients improves disease control and survival.. The study reviewed Stage II and III rectal cancer patients treated with preoperative chemoradiation and resected for cure. Complete pathologic response was defined as no cancer in the resected specimen. The main outcome measures were cancer-specific and disease-free survival in patients achieving a complete pathologic response and a noncomplete pathologic response. Kaplan-Meier curves were evaluated using log-rank analysis.. Eighty-nine rectal cancer patients received neoadjuvant chemoradiation followed by radical resection for cure. Twenty-one patients (24 percent) achieved a complete pathologic response. Median follow-up for the complete pathologic response group was 23.5 months and 31 months for the noncomplete pathologic response group. There were more Stage III patients in the noncomplete pathologic response group than the complete pathologic response group (P = 0.005). Complete pathologic response patients were less likely to receive postoperative adjuvant chemotherapy than noncomplete pathologic response patients (P = 0.004). Cancer-specific and disease-free survival were not statistically different between the two groups. However, a trend was noted toward improved survival and decreased recurrence in association with a complete pathologic response.. Stage III patients were less likely to be in the complete pathologic response group than Stage II patients. Complete pathologic response patients were less likely to receive postoperative adjuvant chemotherapy than noncomplete pathologic response patients. Complete pathologic response after neoadjuvant chemoradiation for rectal cancer patients demonstrated a trend toward improved survival and decreased recurrence compared with noncomplete pathologic response patients.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Female; Fluorouracil; Humans; Leucovorin; Male; Neoplasm Recurrence, Local; Neoplasm Staging; Postoperative Care; Preoperative Care; Radiotherapy Dosage; Radiotherapy, Adjuvant; Rectal Neoplasms; Survival Analysis

The treatment of colorectal cancer with administration of a 2-h infusion of calcium folinate followed by a 24-h infusion of 5-fluorouracil (5-FU) is a standard therapy. Based on newly published data we have applied an infusion of both compounds, 5-FU and calcium folinate, mixed together in an ambulatory pump.. We report on a patient suffering from metastatic rectal cancer. After first and second line chemotherapy we started third line chemotherapy consisting of calcium folinate (1,000 mg) and 5-FU (4,000 mg) mixed together in a total volume of 240 ml in an ambulatory pump and administered over a period of 24 h. After a total of 11 applications the patient developed a port thrombosis resistant to lysis with urokinase. The blocked catheter was surgically explanted and the firm material inside was analyzed.. The material from inside the lumen of the catheter was analyzed using x-ray spectroscopy and a scanning electron microscopy. Both analyses confirmed that the isolated material is calcium carbonate.. This case and the results of the analyses are in accordance with the described problems and results published earlier. A physical and/or chemical in vitro compatibility of 5-FU and calcium folinic acid, without validated clinical data is not sufficient to use this mixture in routine clinical practice.

Topics: Antineoplastic Combined Chemotherapy Protocols; Calcium Carbonate; Catheterization, Central Venous; Catheters, Indwelling; Drug Interactions; Drug Therapy, Combination; Equipment Failure Analysis; Fluorouracil; Humans; Infusion Pumps; Infusions, Intravenous; Leucovorin; Male; Microscopy, Electron; Middle Aged; Neoplasm Staging; Palliative Care; Rectal Neoplasms; Spectrometry, X-Ray Emission

A 71-year-old man underwent low anterior resection for rectal cancer. Two years after the surgery, liver metastasis and local recurrence were found on the CT scan. The first-line treatment was systemic chemotherapy (CPT-11 and 5'-DFUR). Effect was satisfactory for local recurrence, but a new liver tumor was found on the CT scan. The second-line treatment was a hepatic arterial infusion (5-FU) and systemic chemotherapy (UFT). After 4 courses, the liver metastasis was reduced, but after 5 courses, the liver tumors had enlarged. The third-line treatment was a hepatic arterial infusion (5-FU + levofolinate) and systemic chemotherapy (UFT). After 5 courses, the liver tumor disappeared, and no other recurrence was found on the CT scan.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Drug Administration Schedule; Drug Combinations; Floxuridine; Fluorouracil; Hepatic Artery; Humans; Infusions, Intra-Arterial; Irinotecan; Leucovorin; Liver Neoplasms; Male; Neoplasm Recurrence, Local; Rectal Neoplasms; Tegafur; Uracil

A 61-year-old man underwent curative low anterior resection for rectosigmoid colon cancer. Follow-up ultrasonography revealed unresectable multiple liver metastases at 10 months after surgery. Arterial infusion therapy with 5-fluorouracil (5-FU) was given at 1,500 mg every 2 weeks up to a total dose of 37.5 g, resulting in complete remission (CR) of the liver metastases. However, recurrence was seen 4 months after CR. Following partial hepatectomy and local ablation therapy, he received multidisciplinary treatment including local ablation therapy, arterial infusion of 5-FU and mitomycin C, and systemic chemotherapy with 5-FU/Leucovorin/CPT-11. The patient died of liver failure at 3 years and 7 months after the detection of hepatic metastases. If arterial infusion therapy achieves CR of unresectable hepatic metastases from colorectal cancer, the patient may survive for several years with multidisciplinary treatment including surgery, local ablation therapy, and systemic chemotherapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Combined Modality Therapy; Drug Administration Schedule; Fluorouracil; Hepatectomy; Hepatic Artery; Humans; Infusions, Intra-Arterial; Irinotecan; Leucovorin; Liver Neoplasms; Male; Middle Aged; Mitomycin; Rectal Neoplasms; Sigmoid Neoplasms

Chemotherapy combined with 5-FU and l-leucovorin has been reported to elicit a quick response in cases of lower rectal carcinoma. A 65-year-old woman developed pain in the right gluteal region due to locally extended rectal carcinoma, and was treated with intraarterial infusion therapy. The chemotherapy regimen was 5-FU (500 mg/body) and l-leucovorin (175 mg/body) administered over 3 hours once weekly to bilateral reservoirs through an infuser pump. After 2 sessions of the chemotherapy, the gluteal pain decreased, and after 3 sessions, CEA level was confirmed and the patient's QOL began to improve. Side effects of the intraarterial infusion chemotherapy were gluteal dermatitis, leg desensitization, and infection of the circumferential reservoir. Local intraarterial infusion chemotherapy can be safely performed on an outpatient basis, and appears to elicit quick response for locally extended advanced rectal carcinoma.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusion Pumps, Implantable; Infusions, Intra-Arterial; Leucovorin; Lymphatic Metastasis; Rectal Neoplasms; Skin Ulcer

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carcinoembryonic Antigen; Colonic Neoplasms; Fluorouracil; Humans; Leucovorin; Organoplatinum Compounds; Oxaliplatin; Practice Guidelines as Topic; Prognosis; Rectal Neoplasms

Topics: Adenocarcinoma, Mucinous; Adult; Camptothecin; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Neoadjuvant Therapy; Patient Care Planning; Rectal Neoplasms; Rectum; Ultrasonography

In this study, we evaluated the efficacy and tolerability of biweekly irinotecan (CPT-11) plus 5-fluorouracil (5-FU) and folinic acid (FA) regimen (IFL) in patients with advanced stage colorectal cancer.. A total of 28 patients were examined. The median age was 51 years (range, 30-74 years). One treatment cycle consisted of CPT-11 180 mg/m(2) on days 1 and 15; 5-FU 425 mg/m(2) on days 1, 2, 15 and 16; and FA 20 mg/m(2) on days 1, 2, 15 and 16, every 4 weeks. A total of 119 cycles (median, 4.0 cycles) were administered. Of the 28 patients, 18 received the chemotherapy as first line treatment, seven received it as second line and three received it as third line.. An overall objective response rate of 21.5% was achieved in the patient group. However, the overall response rate for the 18 patients receiving first line treatment was 27.7%. The median response duration was 10.5 months (range, 3-19 months). An additional 28.6% of the patients had stable disease for a median duration of 6.5 months (range, 3-8 months). Median time to disease progression was 4.5 months (range, 1-22+ months) and median overall survival time was 11+ months (95% confidence interval, 9-15 months). Toxicities were mild and manageable.. We conclude that biweekly IFL is a practical and tolerable treatment option with a disease control rate of 50.1% in patients with advanced stage colorectal cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Staging; Rectal Neoplasms; Survival Analysis

Capecitabine (Xeloda) is a new orally administered fluoropyrimidine carbamate that was rationally designed to exert its effect by tumor-selective activation. We attempted to evaluate the efficacy and toxicity of preoperative chemoradiation using capecitabine in locally advanced rectal cancer.. Between July 1999 and March 2001, 45 patients with locally advanced rectal cancer (cT3/T4 or N+) were treated with preoperative chemoradiation. Radiation of 45 Gy/25 fractions was delivered to the pelvis, followed by a 5.4 Gy/3 fractions boost to the primary tumor. Chemotherapy was administered concurrent with radiotherapy and consisted of 2 cycles of 14-day oral capecitabine (1650 mg/m(2)/day) and leucovorin (20 mg/m(2)/day), each of which was followed by a 7-day rest period. Surgery was performed 6 weeks after the completion of chemoradiation.. Thirty-eight patients received definitive surgery. Primary tumor and node downstaging occurred in 63% and 90% of patients, respectively. The overall downstaging rate, including both primary tumor and nodes, was 84%. A pathologic complete response was achieved in 31% of patients. Twenty-one patients had tumors located initially 5 cm or less from the anal verge; among the 18 treated with surgery, 72% received sphincter-preserving surgery. No Grade 3 or 4 hematologic toxicities developed. Other Grade 3 toxicities were as follows: hand-foot syndrome (7%), fatigue (4%), diarrhea (4%), and radiation dermatitis (2%).. These preliminary results suggest that preoperative chemoradiation with capecitabine is a safe, well-tolerated, and effective neoadjuvant treatment modality for locally advanced rectal cancer. In addition, this preoperative treatment has a considerable downstaging effect on the tumor and can increase the possibility of sphincter preservation in distal rectal cancer.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Capecitabine; Deoxycytidine; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Radiotherapy Dosage; Rectal Neoplasms

The purpose of this study was to determine the efficacy and toxicity of uracil/ftorafur (UFT) plus oral leucovorin (LV) as first-line chemotherapy for patients with metastatic colorectal cancer and salvage chemotherapy with weekly high-dose 5-fluorouracil (5-FU)/LV 24 h infusion.. Adult patients with no prior chemotherapy for metastatic diseases were enrolled to receive oral UFT 300 mg/m(2)/d plus LV 90 mg/d for 28 days. Treatment was given continuously for 28 days followed by a 7 day rest period from all treatment. For UFT failed patients, weekly 24 h infusion of 5-FU 2600 mg/m(2) plus LV 100 mg/m(2) was used as salvage therapy.. Fifty-one patients with metastatic colorectal cancer were enrolled in the study. The objective response rate was 29.5% [95% confidence interval (CI), 16.8-45.2%] among the 44 evaluable patients and 25.5% in the intent-to-treat population. The median survival for all 51 patients was 16.6 months. The median time to progression was 5.9 months. Diarrhea was the major adverse effect of UFT/LV that made patients reduce dosage. Grade 3 or 4 diarrhea developed in 13.7% of patients. Twenty-six patients were treated with weekly 24 h infusional 5-FU/LV as salvage therapy and only two patients responded.. Our results suggest that this 28 day schedule of UFT/LV regimen may offer a well-tolerated, full oral treatment option with efficacy that appears comparable to that of intravenous 5-FU/LV regimens. Parenteral 5-FU/LV as salvage therapy for UFT refractory patients is not recommended.

Topics: Adult; Aged; Antineoplastic Agents; Colonic Neoplasms; Diarrhea; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Fluorouracil; Humans; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Metastasis; Rectal Neoplasms; Salvage Therapy; Tegafur; Uracil

Epidermal growth factor receptor (EGFR) expression is observed in 50%-70% of colorectal carcinomas and is associated with poor prognosis. The aim of this study was to determine the EGFR expression rate in locally advanced rectal cancer and to analyze whether EGFR expression predicts tumor response to preoperative radiotherapy.. Between December 1997 and October 2000, 45 patients were included. Treatment consisted of preoperative pelvic radiotherapy and, in 21 patients, 2 courses of 5-fluorouracil leucovorin. Surgical resection was performed 4-8 weeks later. Immunohistochemistry for EGFR was determined at the preradiation diagnostic biopsy and in the resected specimens. Immunostaining was performed using EGFR monoclonal antibody (Biogenex, MU 207-UC). Immunohistochemical staining was evaluated according to extension and intensity. We defined positive staining (EGFR+) as extension of 5% or more.. Preoperative treatment resulted in pathologic complete remission in 7 patients (15%), downstaging in 13 patients (29%), and no response in 25 patients (56%). EGFR+ was observed in 29 of 45 tumors (64%) and was associated with neither clinical tumor stage nor clinical nodal stage. The overall response rate was 34% in EGFR+ patients vs. 62% in those who were EGFR- (p = 0.07). Only 1 of the 7 pathologic complete remission patients was EGFR+ (p = 0.003).. EGFR is expressed in a significant number of locally advanced rectal tumors. EGFR expression is an indicator for poor response to preoperative radiotherapy in advanced rectal carcinoma.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Combined Modality Therapy; ErbB Receptors; Female; Fluorouracil; Humans; Immunohistochemistry; Leucovorin; Male; Middle Aged; Prognosis; Rectal Neoplasms; Remission Induction

Chemotherapy with combined administration of 5-FU and l-Leucovorin has been reported to be effective for advanced rectal cancer. A 61-year-old woman with a huge, locally extended advanced rectal cancer was treated with intra-arterial infusion therapy via internal iliac artery. Catheters were inserted from the bilateral femoral arteries to the opposite internal iliac arteries and the bilateral upper and lower gluteal arteries and lateral sacral artery were embolized with a metallic coil. The port was positioned under the skin of her lower abdominal wall. The chemotherapy regimen was 5-FU (500 mg/body) and l-Leucovorin (250 mg/m2), administered over 5 hours once weekly to bilateral reservoirs through an infuser pump. After 5 sessions of the chemotherapy, the perineal pain decreased and the patient no longer needed morphine. Following 34 administrations (at 10 months) of this regimen, reductions of tumor size on pelvic CT and CEA level were confirmed. Side effects of the intra-arterial infusion chemotherapy were pygal dermatitis, leg desensitization, infection of circumferential reservoir and obstruction of the catheter due to flection were observed. Local intra-arterial infusion chemotherapy via the internal iliac artery appears to be effective for local advanced rectal cancer.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Iliac Artery; Infusions, Intra-Arterial; Leucovorin; Middle Aged; Rectal Neoplasms

Recently, angiogenesis has gained an increasing interest as a prognostic factor in a variety of solid tumours. In this study we aimed to assess the prognostic role of serum vascular endothelial growth factor (VEGF), basic fibroblast growth factor (b-FGF) and nitric oxide (NO) levels in patients with colorectal carcinoma (CRC).A total of 52 consecutive colorectal cancer patients with stage I to IV disease was included. In addition to routine laboratory and staging procedures, serum VEGF, b-FGF levels, and nitrate levels as a surrogate marker for in-vivo NO production were assayed. Serum VEGF concentrations, adjusted to the platelet count were found to be a significant factor for overall survival in univariate analysis (P=0.033). A new angiogenic index (AI), derived from serum VEGF and nitrate concentrations, was established. AI is the only independent prognostic factor of survival in all patients (P=0.008, Cox regression analysis). Likewise, AI is also significant prognostic factor for disease-free survival (DFS) in patients with operable CRC (P=0.032, Cox regression analysis). In conclusion, serum VEGF and NO levels have prognostic role in patients with CRC and the new angiogenesis index using the serum levels of the factors seem to be useful.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Camptothecin; Carcinoembryonic Antigen; Chemotherapy, Adjuvant; Cisplatin; Colonic Neoplasms; Colorectal Neoplasms; Disease-Free Survival; Endothelial Growth Factors; Female; Fibroblast Growth Factor 2; Fluorouracil; Follow-Up Studies; Humans; Intercellular Signaling Peptides and Proteins; Irinotecan; Leucovorin; Life Tables; Lymphokines; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Proteins; Neoplasm Recurrence, Local; Neovascularization, Pathologic; Nitrates; Nitric Oxide; Organoplatinum Compounds; Oxaliplatin; Prognosis; Proportional Hazards Models; Rectal Neoplasms; Survival Analysis; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Dihydropyrimidine dehydrogenase (DPD) is a rate-limiting enzyme that metabolizes 5-fluorouracil (5-FU). We report a patient with metachronous liver metastasis from rectal cancer with low expression of DPD, who demonstrated complete response to chemotherapy comprising 5-FU, Leucovorin, and UFT. A 53-year-old man underwent macroscopically curative proctectomy with coloanal anastomosis for lower rectal cancer (Curability B). The DPD level in the primary tumor determined by an enzyme-linked immunosorbent assay was extremely low (10.3 U/mg.protein). Three months postoperatively, 5-FU (333 mg/m2) + Leucovorin (200 mg/m2) therapy (once a week for 3 weeks with a one-week rest interval, repeatedly) was started as an adjuvant therapy. However, computed tomography demonstrated a solitary liver metastasis 3 cm in size 1 month later. Chemotherapy was continued with dose escalation of 5-FU (500 mg/m2) and with oral administration of UFT-E (400 mg/body, daily). Five months later, computed tomography did not detect the liver metastasis, and this finding was maintained for two months (complete response). This case provides evidence that a low expression of DPD in the primary lesion is related to a favorable response of liver metastasis to 5-FU-based systemic chemotherapy.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Drug Combinations; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Rectal Neoplasms; Remission Induction; Tegafur; Uracil

We report the case of 66-year-old male with recurrent rectal cancer which responded to chemotherapy using CPT-11, Isovorin, and 5-fluorouracil (5-FU). CPT-11 was administered at 40 mg (90 min i.v.) x 3 day/week, and Isovorin and 5-FU were administered at 25 mg (bolus) and 250 mg (continuous) x 5 day/week by intraarterial infusion. Three cycles of this weekly regimen resulted in regression of tumors in the iliac region with remission of the lameness caused by iliac pain. The serum CEA level decreased from 13.1 ng/ml to 0.5 ng/ml. The patient has undergone 13 cycles of the regimen modified for outpatients (CPT-11 at 40 mg x 3 day/week plus Isovorin at 25 mg and 5-FU at 250 mg 1 day/week) with inhibitions of tumor regrowth and improved serum CEA level for more than 12 months. The current case suggests that weekly low-dose CPT-11/Isovorin/5-FU may have a potent therapeutic effect against recurrent rectal cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Drug Administration Schedule; Fluorouracil; Humans; Infusions, Intra-Arterial; Infusions, Intravenous; Irinotecan; Leucovorin; Male; Neoplasm Recurrence, Local; Rectal Neoplasms

Liver cryosurgery is one of the treatment options for unresectable liver metastases. Indications for the use of this treatment instead of classic surgery are bilobar disease, location of the tumor at an irresectable anatomic site, and comorbid conditions of the patient. Possible complications of cryosurgery are hemorrhage, coagulopathy, pneumonia, pleural effusion, abdominal abscess, and bile fistula. We describe a patient in whom a hepatobronchial fistula developed after cryosurgery. The patient had cryosurgery because of an unresectable liver metastasis in a Dukes' C rectal carcinoma. More details are given in the case report. To our knowledge, a hepatobronchial fistula as a complication of cryosurgery has never been reported. It therefore should be added to the list of possible cryosurgery complications.

Topics: Antimetabolites, Antineoplastic; Bronchial Fistula; Carcinoma; Cryosurgery; Fistula; Fluorouracil; Humans; Leucovorin; Liver Diseases; Liver Neoplasms; Male; Middle Aged; Postoperative Complications; Rectal Neoplasms; Ultrasonography

Mesorectal involvement is a common feature in rectal tumors. Neoplastic foci can be identified at pathologic examination of the mesorectum, but their incidence and prognostic significance remain to be defined.. A series of 77 patients with extraperitoneal rectal cancer, resected with total mesorectal excision, entered the study. After fixation, the excised specimens were submitted to serial transverse sections and staining. Direct tumor infiltration, lymph node involvement, and neoplastic microfoci in the mesorectum were investigated. Patients with mesorectal foci were compared with those without deposits with regard to clinical and pathologic parameters; different patterns of foci (endovasal, endolymphatic, perineural, isolated) were also considered. Univariate and multivariate analyses were used to evaluate the impact on survival rate.. Neoplastic mesorectal involvement was found in 64 patients (83.1 percent). Direct tumor infiltration was detected in 66.2 percent, node involvement in 28.6 percent, microscopic foci in 44.2 percent of cases (endovasal in 11.7 percent, endolymphatic in 15.7 percent, perineural in 26 percent, isolated in 14.3 percent). In 7 cases (10.9 percent) microfoci alone (without any kind of other mesorectal involvement) were detected. Deposits were found in 18.8 percent of TNM Stage I tumors, in 46.9 percent of Stage II and in 59.3 percent of Stage III cancers. Similar incidence was found in patients treated with integrated therapies and surgery alone (43.3 vs. 44.7 percent, P = not significant). Poorer median (44.5 vs. 57 months, P = 0.04) five-year overall survival rate (43.4 vs. 63.3 percent, P = 0.016) and disease-free survival rate (43.3 vs. 57.7 percent, P = 0.048) were observed in patients with microscopic foci compared with those without deposits. Tumor configuration was found to be a independent prognostic factor for both overall and disease-free survival rates; furthermore, endolymphatic, perineural, and isolated foci significantly affected overall survival rate, while TNM staging affected disease-free survival rate.. The incidence of neoplastic foci in the mesorectum is high, even in early staged tumors and despite aggressive preoperative treatment. They seem to affect prognosis. Such features should, therefore, be considered when local excision of the tumor is planned. Presence of mesorectal foci should modify conventional staging of the rectal tumor.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Disease-Free Survival; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Mitomycin; Neoplasm Invasiveness; Neoplasm Staging; Peritoneal Neoplasms; Prognosis; Radiotherapy, Adjuvant; Rectal Neoplasms; Rectum

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Chills; Fever; Fluorouracil; Humans; Hypotension; Infusions, Intravenous; Leucovorin; Lung Neoplasms; Male; Middle Aged; Nausea; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms; Vomiting

Information in the literature regarding salvage treatment for patients with locally recurrent colorectal cancer who have previously been treated with high or moderate dose external beam irradiation (EBRT) is scarce. A retrospective review was therefore performed in our institution to determine disease control, survival, and tolerance in patients treated aggressively with surgical resection and intraoperative electron irradiation (IOERT) +/- additional EBRT and chemotherapy.. From 1981 through 1994, 51 previously irradiated patients with recurrent locally advanced colorectal cancer without evidence of distant metastatic disease were treated at Mayo Clinic Rochester with surgical resection and IOERT +/- additional EBRT. An attempt was made to achieve a gross total resection before IOERT if it could be safely accomplished. The median IOERT dose was 20 Gy (range, 10--30 Gy). Thirty-seven patients received additional EBRT either pre- or postoperatively with doses ranging from 5 to 50.4 Gy (median 25.2 Gy). Twenty patients received 5-fluorouracil +/- leucovorin during EBRT. Three patients received additional cycles of 5-fluorouracil +/- leucovorin as maintenance chemotherapy.. Thirty males and 21 females with a median age of 55 years (range 31--73 years) were treated. Thirty-four patients have died; the median follow-up in surviving patients is 21 months. The median, 2-yr, and 5-yr actuarial overall survivals are 23 months, 48% and 12%, respectively. The 2-yr actuarial central control (within IOERT field) is 72%. Local control at 2 years has been maintained in 60% of patients. There is a trend toward improved local control in patients who received > or =30 Gy EBRT in addition to IOERT as compared to those who received no EBRT or <30 Gy with 2-yr local control rates of 81% vs. 54%. Distant metastatic disease has developed in 25 patients, and the actuarial rate of distant progression at 2 and 4 years is 56% and 76%, respectively. Peripheral neuropathy was the main IOERT-related toxicity; 16 (32%) patients developed neuropathies (7 mild, 5 moderate, 4 severe). Ureteral narrowing or obstruction occurred in seven patients. All but one patient with neuropathy or ureter fibrosis received IOERT doses > or =20 Gy.. Long-term local control can be obtained in a substantial proportion of patients with aggressive combined modality therapy, but long-term survival is poor due to the high rate of distant metastasis. Re-irradiation with EBRT in addition to IOERT appears to improve local control. Strategies to improve survival in these poor-risk patients may include the more routine use of conventional systemic chemotherapy or the addition of novel systemic therapies.

Topics: Adult; Aged; Analysis of Variance; Antimetabolites, Antineoplastic; Colonic Neoplasms; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Radiotherapy Dosage; Rectal Neoplasms; Retrospective Studies; Salvage Therapy; Survival Analysis

Oxaliplatin could increase the efficacy of fluorouracil (5-FU)/folinic acid chemoradiotherapy in rectal cancer. We tested three dose levels to identify a feasible oxaliplatin dose for combination therapy.. Between February 1998 and April 2000, we included 17 rectal adenocarcinoma patients in a single-center phase I study. Patients had T4 rectal carcinoma, T1-T3 disease with colostomy refusal, or potentially operable T2/T3 M1 requiring local treatment. Pelvic radiotherapy was 45 Gy over 5 weeks, 1.8 Gy/fraction, with concomitant chemotherapy weeks 1 and 5. Chemotherapy was oxaliplatin 80, 100, or 130 mg/m2 2-hour infusion on day 1 followed by L-folinic acid 100 mg/m2/d intravenous bolus, and 5-FU 350 mg/m2/d continuous infusion on days 1 to 5 (FolfoR1). Six patients refusing surgery received additional contact radiotherapy +/- brachytherapy. Dose escalation proceeded if less than two of six patients had dose-limiting toxicity (DLT) at a given dose-level.. All except two patients completed treatment; patients at level 1 (prolonged grade 1 thrombocytopenia) and level 3 (prolonged cold-related dysesthesia) had no second chemotherapy course. Median follow-up is 14 months (range, 2 to 28 months). One elderly patient at dose level 1 had DLT asthenia, severe diarrhea and vomiting, and more than 10% weight loss. There were no other DLTs and no severe rectitis or gastrointestinal toxicity. There were objective responses at all doses and no progressions. Eight patients underwent radical surgery after chemoradiotherapy. Two had complete pathologic responses.. FolfoR1 seems feasible and effective. Dose escalation did not increase toxicity. Although the MTD was not reached in this study, we recommend oxaliplatin 130 mg/m2 for phase II studies because it is the dose determined from studies in metastatic patients with no toxicity when given concurrently with radiation.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms

Topics: Antimetabolites, Antineoplastic; Brachytherapy; Combined Modality Therapy; Drug Therapy, Combination; Female; Fluorouracil; Humans; Leucovorin; Lymphatic Metastasis; Male; Neoplasm Recurrence, Local; Postoperative Care; Preoperative Care; Prognosis; Radiotherapy Dosage; Radiotherapy, Adjuvant; Rectal Neoplasms; Risk Factors; Time Factors; Tomography, X-Ray Computed

Our aim was to ascertain whether or not the response to preoperative chemoradiotherapy for rectal cancer is associated with p27kip1 and p53 protein expression.. Thirty-eight patients (27 male, 11 female) with a mean age of 59 years (age range 33-87) and stage II-III rectal cancer received preoperative chemoradiotherapy (45-50.4 Gy; 5-FU 350 mg/m2/day and leucovorin 10 mg/m2/day). Thirty-one underwent low anterior resection; seven underwent abdominoperineal excision. Endoscopic tumor biopsies, performed before adjuvant therapy, were evaluated for: histologic type, tumor differentiation, mitotic index, and p27kip1 and p53 protein expression which were immunohistochemically determined. p53 expression was graded as: a) absent or present in < or =10% of tumor cells; b) present in 11-25%; c) present in 26-75%; and d) present in >75% of tumor cells. p27kip1 expression was assessed using both light microscopy (percent of stained cells x10 HPF) and cytometry with an image analysis workstation. Tumor response, ascertained with histology, was classified using a scale from 0 (no response) to 6 (complete pathologic response).. The mitotic index for the endoscopic biopsies was low in 14 cases, moderate in 17 cases, and high in 7 cases. p53 protein expression was found in 21 (a), 3 (b), 3 (c), and 11 (d) cases. The mean percentage of cells expressing the p27kip1 protein was 34 (range 0-77.14%). A close correlation was found between cytometric and light microscopy findings for p27kip1 (r2 = 0.92, P = .0001). Tumor differentiation was good in 5 cases, poor in 2 cases, and moderate in the remaining 31 cases. While the response to adjuvant therapy was good/complete in 25 (65.78%) cases, it was absent/poor in 13 (34.21%) cases. Univariate analysis associated type of adjuvant therapy (chemoradiotherapy, P = .0428) and p27kip1 protein lower expression (P = .0148) with a poor response to adjuvant treatment. Stepwise linear regression found overexpression of p53 and p27kip1 and young age to be independent variables that were linked to a good response to adjuvant therapy.. Lack of p27kip1 and p53 protein expression in rectal cancer is associated with a poor response to preoperative adjuvant therapy.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Cell Cycle Proteins; Combined Modality Therapy; Cyclin-Dependent Kinase Inhibitor p27; Female; Fluorouracil; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Prognosis; Rectal Neoplasms; Retrospective Studies; Treatment Outcome; Tumor Suppressor Protein p53; Tumor Suppressor Proteins

A 69-year-old-man was referred to our hospital because of rectal cancer with multiple liver metastases. He was initially treated by hepatic arterial chemotherapy using an infusion reservoir (HACR) and radiotherapy for the rectal cancer. An abdomino-perineal resection and extended left lobectomy of the liver were performed and resulted in a reduction in size of the liver tumor. He was diagnosed as having a recurrent liver metastasis (S7) at 3 months after the operation, and was retreated by HACR in the outpatient clinic. A partial hepatectomy was reperformed at 6 months after the operation. Adjuvant hepatic arterial infusion chemotherapy (HAIC) was performed on an outpatient basis and the patient is doing well without recurrence or relapse. Preoperative arterial chemotherapy for metastatic liver tumor may be of some benefit for certain patients with far advanced colorectal carcinoma.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Fluorouracil; Hepatectomy; Hepatic Artery; Humans; Infusions, Intra-Arterial; Leucovorin; Liver Neoplasms; Male; Prognosis; Rectal Neoplasms; Rectum

Prospective randomized clinical trials have shown the effectiveness of combined adjuvant 5-fluorouracil-based chemotherapy and radiotherapy after surgical resection of rectal cancer. To assess toxicity of this therapy, prospective data were collected from 236 Asian rectal cancer patients treated with combined 5-fluorouracil-based chemotherapy and radiotherapy after surgery. Almost 82% of patients completed planned therapy. Grade 3 and 4 diarrhea, stomatitis, and granulocytopenia occurred in approximately 18-21% of patients. There were two treatment-related deaths from granulocytopenia and sepsis. With median follow-up of 3.5 years, median disease-free and overall survival was 75 and 88 months, respectively. In conclusion, combined adjuvant 5-fluorouracil-based chemotherapy and radiotherapy after surgical resection of rectal cancer is tolerable in Asian patients with moderate toxicity.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Agranulocytosis; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Combined Modality Therapy; Diarrhea; Disease-Free Survival; Drug Evaluation; Female; Fluorouracil; Humans; Leucovorin; Life Tables; Lymph Node Excision; Male; Middle Aged; Neoplasm Metastasis; Postoperative Period; Prospective Studies; Radiotherapy, Adjuvant; Rectal Neoplasms; Sepsis; Singapore; Stomatitis; Survival Analysis

Despite of advanced surgical technique and multimodality therapy results following secondary resection of local recurrence after rectal cancer are discussed controversially.. Between 1990 and 1999 81 patients with local recurrence of rectal cancer were treated at our surgical department. Median age was 63 years, 62 % of patients were male. 98 % of recurrences were in local advanced stage (74 % = rT4, 25 % = rT3), 44 % of patients had synchronous distant metastases.. 32 patients underwent resection of recurrent rectal cancer. Potential curative surgery was possible in 56 % of resections. Extended resections of adjacent organs were necessary in 21 patients. The 4-year survival in the curative group was 44 % compared to 19 % in patients with microscopic or gross residual disease.. Optimistic long-term results in recurrent rectal cancer can only be achieved after curative resection. Preoperative radiochemotherapy in advanced cancers increases curative resection and probably survival rate.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Antimetabolites, Antineoplastic; Combined Modality Therapy; Drug Therapy, Combination; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Preoperative Care; Radiotherapy Dosage; Rectal Neoplasms; Time Factors

Preoperative chemoradiotherapy followed by radical surgical resection has been the preferred treatment for patients presenting with locally advanced distal rectal carcinoma at our institutions. We postulated that chemoradiotherapy-induced pathologic response of the primary tumor would identify which patients would be candidates for local excision as definitive surgical therapy.. A retrospective analysis of 60 patients with palpable, locally advanced, distal rectal adenocarcinomas treated from 1995 to 2000 was performed. All patients received preoperative chemoradiotherapy consisting of 5-fluorouracil (325 mg/m(2)) and leucovorin (20 mg/m(2)) by bolus infusion on Days 1 through 5 and 29 through 33 delivered concurrently with at least 45.0 to 50.4 Gy of pelvic radiation, followed six to eight weeks later by radical surgery and then adjuvant chemotherapy.. Among 60 patients (20 females) there was a mean age of 58.7 (28-84) years. Clinical staging was as follows: Stage II, 14 patients (23 percent); Stage III, 35 patients (58 percent); and Stage IV, 11 patients (18 percent). Pathologic examination revealed that negative margins were obtained in 58 patients (97 percent). Downstaging to T0-2N0 was achieved in 17 patients (28 percent), with five (8 percent) achieving a pathologically complete response. Lymph nodes were positive in 24 patients (40 percent) despite chemoradiotherapy. Pathologic node positivity was found in 0 of 5 pT0 patients, 9 (41 percent) of 22 pT1 or pT2, and 15 (45 percent) of 33 pT3. Clinical stage, tumor size, pathologic stage, and adverse histologic features could not reliably predict pN0 status, except pT0 (5 patients only).. Preoperative chemoradiotherapy often downsizes and downstages locally advanced rectal carcinoma. Neither pretreatment clinical characteristics, response to preoperative chemoradiotherapy, or pathologic features reliably predict pN0 status. Therefore, local excision is not recommended as an alternative to radical surgery for locally advanced adenocarcinoma of the distal rectum regardless of the response of the primary tumor to preoperative chemoradiotherapy.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Combined Modality Therapy; Feasibility Studies; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Proctoscopy; Rectal Neoplasms; Rectum

A wide range of tumor response is seen amongst patients with the same stage of colorectal cancer, even with the use of uniform chemotherapy. The significant economic and personal impact of chemotherapy provides the impetus for the identification of markers of response for use in guiding patient treatment. However, practical constraints prevent evaluation of all putative markers in a definitive manner. In this study, the enrichment approach was evaluated by examining the expression of a panel of putative response markers in selected patient populations with advanced colorectal cancer (i.e., those demonstrating the best and the poorest clinical response to a standardized 5-fluorouracil/folinic acid chemotherapy regimen). Patients showing a good response had a significantly increased survival when compared with poor responders (P=0.0013). Markers were then ranked for clinical importance based on differences in expression between the two groups. This allows for the relatively rapid and inexpensive investigation of multiple markers, using defined patient groups. Bcl-2 overexpression in primary colorectal tumor specimens was found to correlate with clinical response of metastatic deposits to chemotherapy (P=0.044), as did the site of the primary tumor (P=0.011). However, no clear association was observed between response status and the other examined factors (p53, PCNA, TP, MMPs 1, 2 or 9, TIMPs 1 or 2, TS, Dukes' stage at initial diagnosis, histological grade, sex or age). This approach has allowed prioritization of markers of clinical response on which larger, statistically definitive studies will be performed.

Topics: Adult; Aged; Biomarkers, Tumor; Colonic Neoplasms; Colorectal Neoplasms; Female; Humans; Leucovorin; Liver Neoplasms; Male; Matrix Metalloproteinase 1; Matrix Metalloproteinase 2; Middle Aged; Neoplasm Metastasis; Predictive Value of Tests; Proliferating Cell Nuclear Antigen; Proto-Oncogene Proteins c-bcl-2; Rectal Neoplasms; Survival Rate; Thymidylate Synthase; Tissue Inhibitor of Metalloproteinases; Tumor Suppressor Protein p53

Management of locally recurrent colorectal adenocarcinoma represents a significant challenge. Many of these tumors adhere to or invade into vital pelvic structures rendering surgery or external beam radiotherapy (EBRT) as palliative treatment. Therefore, a treatment approach was developed to evaluate the role of high-dose-rate intraoperative brachytherapy (HDR-IORT) and surgery as a component of therapy in the management of locally recurrent colorectal cancer. This is an update of our preliminary report with longer follow-up and larger patient numbers.. Between January 1992 and September 1998, 74 patients with locally recurrent rectal cancer were treated with surgery and HDR-IORT. Additional EBRT was given to 29 patients, and 33 patients received 5-fluorouracil based chemotherapy. All patients underwent complete gross resection, and 21 of 74 had positive microscopic margin. The dose of HDR-IORT ranged from 10 to 18 Gy.. With a median follow-up of 22 months, the 5-year local control, distant metastasis disease-free, disease-free, and overall survival rates were 39%, 39%, 23%, and 23%, respectively. The only predictor of improved local control was a negative margin of resection with a 5-year local control rate of 43%, compared to 26% in those with positive margin (p = 0.02). For overall survival, a negative microscopic margin (p = 0.04) and the use of IORT + EBRT (p = 0.04) were significant predictors of improved survival. The incidence of peripheral neuropathy was 16%.. The results with HDR-IORT in this group of patients are encouraging. Further improvements in local and distant control are still needed.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Brachytherapy; Colonic Neoplasms; Combined Modality Therapy; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Radiation Injuries; Rectal Neoplasms; Treatment Failure

To report 5-fluorouracil in combination with folinic acid as a cause of severe nonischemic heart failure and to demonstrate the potential usefulness of an intra-aortic balloon pump.. Case report.. An adult, 19-bed medical/surgical intensive care unit of a university hospital.. A patient, who developed severe heart failure secondary to 5-fluorouracil infusion with low-dose folinic acid, which was introduced to treat a rectal cancer, was transferred from a cancer institute to our intensive care unit 4 days after the treatment was initiated.. Electrocardiography, determination of level of cardiac enzymes, echocardiography, radial arterial catheterization, mechanical ventilatory support, continuous venovenous hemodialysis, vasopressors, and secondary intra-aortic balloon pump.. During shock, the patient's systolic blood pressure progressively decreased to 70 mm Hg, despite inotropic agents and vasopressors. Transesophageal echocardiography showed a calculated left ventricular ejection fraction within 20% with global hypokinesia. Electrocardiography showed sinus tachycardia with only nonspecific ST-T changes. Results of serial determination of levels of cardiac enzymes were not significant for myocardial infarction. Treatment with an intraaortic balloon pump was initiated and resulted in a dramatical improvement within 48 hrs. The patient was gradually weaned from vasopressors and the intra-aortic balloon pump. By the tenth day, echocardiography showed a septoapical hypokinesia with a 50% left ventricular ejection fraction. On the 30th day, the echocardiography was considered normal.. Intravenous 5-fluorouracil in combination with low doses of folinic acid can induce severe nonischemic heart failure. In such a case, an intra-aortic balloon pump could be useful by providing left ventricular function support when inotropic agents and vasopressors fail to restore normal hemodynamics.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Critical Care; Drug Monitoring; Drug Therapy, Combination; Echocardiography, Transesophageal; Female; Fluorouracil; Heart Failure; Humans; Intra-Aortic Balloon Pumping; Leucovorin; Rectal Neoplasms; Risk Factors; Stroke Volume; Time Factors; Vasoconstrictor Agents; Ventricular Function, Left

With the intention to achieve tumor reduction and thereby increase R0-resection rate, preoperative radiochemotherapy is increasingly applied in locally advanced rectum cancer. Along with the advantages of prior therapy, a delay of surgical treatment occurs which might despite continuing therapy give way to local tumor progression or metastatic disease.. Since 1993 we have treated locally advanced rectum carcinomas by preoperative radiotherapy according to a preoperative study protocol. We analyzed the incidence of local tumor progression or metastases during the 12 weeks of preoperative treatment. Hundred and fifteen patients with histologically proven primary rectum carcinoma without evidence of regional or distant metastases and endosonographically determined infiltration depth of stage T3 or more underwent preoperative radiochemotherapy between 3/1993 and 10/1999. Hundred and eight patients (88 times uT3 and (20 times uT4) have been operated and examined afterwards with respect to response to prior treatment. Before and after preoperative therapy, endorectal ultrasound was performed to evaluate local response. Distant metastatic manifestations were excluded by radiography and ultrasound scanning.. A reduction of the infiltration depth was observed in 55 patients (51%). Tumor size remained unchanged in 50 patients (46%). Only 3 patients (3%) showed tumor growth in histological assessment. Fifty-seven patients (53%) showed no change in lymph node status after preoperative therapy, whereas lymph node metastases were detected in 11 patients (10%) who were judged uN0 preoperatively. We discovered metastases in 6 patients (6%) after preoperative therapy.. During preoperative therapy, tumor progress is not entirely evitable. Considering the lack of precision in pretherapeutic staging diagnostics, we conclude that delays due to therapeutic regimen are responsible for prognostic disadvantage in only a small number of patients.

Topics: Antimetabolites, Antineoplastic; Combined Modality Therapy; Endosonography; Fluorouracil; Humans; Leucovorin; Neoplasm Metastasis; Preoperative Care; Radiotherapy Dosage; Rectal Neoplasms; Rectum; Time Factors

We experienced 5 cases of liver metastases from colorectal cancer, in which hepatic resection was carried out after down sizing by hepatic arterial infusion chemotherapy. In addition, a histological study about the effect of chemotherapy on the liver tumor was performed. Primary lesions were located at the sigmoid colon (2), cecum (1), descending colon (1) and rectum (1). We carried out hepatic arterial infusion chemotherapy using mainly 5-FU. The total amount of 5-FU was 10-81 g. Tumor volumes were reduced by 12.5-24%, and they were judged PR. However, surgery was indicated due to obstruction of the proper hepatic artery or other side effects. Postoperative courses were uneventful and the hospital stays were from 17-61 days, and all patients were still alive in tumor-free condition at writing. By the histological study of the excised specimen, we recognized not only remarkable fibrous changes or calcifications but also overt viable cancerous cells. We conclude that the option of hepatic resection after controlling the development of the cancer by hepatic arterial infusion chemotherapy is a rational strategy of treatment for liver metastasis from colorectal cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Colonic Neoplasms; Combined Modality Therapy; Drug Administration Schedule; Epirubicin; Female; Fluorouracil; Hepatectomy; Hepatic Artery; Humans; Infusions, Intra-Arterial; Leucovorin; Liver Neoplasms; Male; Middle Aged; Rectal Neoplasms

Tegafur-uracil has become an important regimen in the treatment of metastatic colorectal cancer. Tegafur is a prodrug that is converted to 5-fluorouracil (5-FU) and has been reported to be less toxic and to have a higher therapeutic index. The additional advantage of tegafur is oral administration, an important consideration to improve the quality of life in these patients. Tegafur in combination with uracil is thought to have greater anti-tumor activity due to the inhibitory effect of uracil on the degradation of 5-FU by hepatic dihydropyrimidine dehydrogenase. Tegafur with folinic acid has been reported with modest efficacy and acceptable toxicity. The purpose of this study was to evaluate the effectiveness and toxicity profile of oral tegafur-uracil plus folinic acid in Chinese patients with metastatic colorectal cancer.. Between May 1998 and August 1999, 40 patients with metastatic colorectal carcinoma were enrolled in this study. All the patients had to have measurable lesions. The initial dose of tegafur-uracil was 300 mg/m2/day for 28 days, followed by a 7-day rest period. Folinic acid was administered orally at a dose of 60 mg/day concurrently with tegafur-uracil. For patients with neutrophil count <1500/microl or a platelet count <100,000/microl after treatment, the treatment was postponed for a maximum of 2 weeks. After that time, if the neutrophil count was 1000-1500/microl and the platelet count was 70,000-100,000 microl, the dose of tegafur-uracil was reduced by 50%, and if lower values resulted, the treatment was discontinued.. Forty patients received a total of 318 courses of treatment and a response rate of 32.5% (95% CI, 18-47%), including five complete remissions and eight partial remissions, was achieved. Toxicity was mild and generally tolerable. Gastrointestinal toxicities, including diarrhea, nausea and vomiting, were the major side effects. Seven incidences (17.5%) of grade 3-4 gastrointestinal toxicity were observed. Hematological toxicities were minimal with no evidence of severe (grade 3 or 4) leukopenia and thrombocytopenia. No episode of hepatic, renal, cardiac or neurological toxicity occurred. Two patients (5%) developed transient painful fissuring erythroderma over their palms and soles (the hand-foot syndrome).. The data from our study indicate that oral tegafur-uracil plus folinic acid is an active and tolerable first-line treatment for Chinese patients with metastatic colorectal cancer, with the additional advantage of being easily administered at home.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Female; Humans; Leucovorin; Male; Middle Aged; Nausea; Rectal Neoplasms; Tegafur; Uracil; Vomiting, Anticipatory

Randomized Swedish studies demonstrate the efficacy of a 5-fraction course of preoperative radiotherapy for rectal carcinoma. The present study evaluates the results in a single U.S. institution over a 20-year period with a similar regimen.. During the period of 1975-1995, 83 patients received pelvic radiotherapy of 20 Gy/5 fractions, followed by immediate surgery for rectal cancer. These patients represented 21% of cases receiving preoperative treatment; the remainder received 45-50 Gy preoperatively. The 5-fraction course was used for lesions deemed readily resectable but too bulky for conservative endocavitary treatment. Since 1990, it has been our policy to administer postoperative chemotherapy to medically fit patients who prove to have pathologic Stage II or III disease. Patient characteristics including age (mean 65 years, range 23-90), gender (45% male), and location within the rectum were comparable to our previously reported cases that received 45 Gy/25 fractions preoperatively. However, the group selected for 5 fractions preoperatively had relatively fewer lesions that were tethered (20% vs. 61%), circumferential (11% vs. 20%), or near obstructing (1% vs. 16%).. With a post treatment follow-up of 1-15 years (mean 4.7), there have been 3 local failures and 12 distant failures, with an actuarial local control of 95%, and disease-specific survival of 77% at 5 and 10 years. Grade > or = 3 perioperative or late toxicity occurred in 11 cases (13%), including 3 (3.5%) late bowel obstructions. Stage II or III disease was found in 56% of the cases, 74% of which were free of disease at last follow-up. However, patients with Stage II or III lesions that were significantly tethered or fixed had a 40% greater likelihood of recurring than similar stage lesions that were, at most, slightly tethered. Sphincter-preserving surgery was possible in 60% of the patients. In recent years, postoperative chemotherapy has been administered to 16 patients with Stage II or III disease; this has been well tolerated, with only 1 late toxicity (cystitis managed medically). When compared with a matched group of cases receiving conventionally fractionated preoperative radiation, there were no significant differences in perioperative morbidity and nonradiotherapeutic cost generating factors (length of hospital stay, duration of postoperative antibiotics, blood loss at surgery).. Patients with resectable rectal cancer who received 20 Gy/5 fractions preoperative radiotherapy to the pelvis had excellent local and distant control of disease. These patients were able to undergo sphincter-preserving surgery and postoperative chemotherapy. It would be of interest to conduct a randomized trial comparing short course with longer course (45 or 50 Gy) preoperative radiotherapy for resectable T3 lesions. The results of this study suggest that, in general, differences in toxicity, local control, and disease-free survival would probably be < 10%. However, since the results of this study suggest that patients with significantly tethered lesions may be better served with the higher dose and longer duration course of radiation, clinical degree of fixation should be included as a stratification parameter, and stopping criteria should be included for tethered lesions.

Topics: Adult; Aged; Aged, 80 and over; Antidotes; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Disease-Free Survival; Dose Fractionation, Radiation; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Rectal Neoplasms; Treatment Failure

The prognosis of patients with inguinal lymph node metastases from rectal adenocarcinoma is poor. The purpose of this study is to analyze the clinical behavior and response to different therapies in a group of these patients.. The medical records of 32 patients with inguinal lymph node metastases from rectal adenocarcinoma, diagnosed between January 1985 and December 1996, were retrospectively analyzed. The cohort was divided into: Group A (synchronous), and Group B (metachronous), according to the time of diagnosis.. There were 17 males and 15 females, with a mean age of 53.5+/-13.8 years. Bilateral inguinal lymph node metastases were diagnosed in 17 patients, and unilateral in 15 patients. Fourteen of 18 patients in Group A (78%) and 13 of 14 patients (93%) in group B, respectively, had concomitantly extrapelvic metastatic disease. Seventeen patients in Group A treated with colostomy + chemoradiotherapy (45 Gy/20 fractions to the pelvis and groin area + 5-fluorouracil 450 mg/m2/weekly) had a progressive metastatic disease; the remaining patient was lost to follow-up after an abdominoperineal resection plus superficial groin dissection. Median survival was 8 months (range, 4-30 months). Overall 5-year survival was 0%. Ten patients in Group B were treated with chemoradiotherapy (50 Gy/25 fractions + 5-fluorouracil 450 mg/m2 + leucovorin 30 mg/m2); three patients received supportive care only, and one patient was treated with a groin dissection. All of them died of disseminated metastatic disease at a median of 13 months (range, 6-57 months). Overall 5-year survival was 0%.. The presence of inguinal metastases in patients with rectal cancer heralds systemic disease and, due to a poor response to the different therapies, only palliative treatment should be indicated.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colostomy; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Radiotherapy Dosage; Rectal Neoplasms; Retrospective Studies; Survival Analysis

Topics: Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Denmark; Drug Costs; Fluorouracil; Health Priorities; Humans; Leucovorin; Palliative Care; Rectal Neoplasms

The report of a series of 20 patients with the aim of trying to specify the implications of pelvic exenteration for rectal cancer.. From 1986 to 1996, 20 total pelvic exenterations were performed for rectal adenocarcinoma. This retrospective study included locally extended carcinomas (n = 10), and recurrences (n = 10) after anterior resection (n = 7), and after abdominoperineal resection (n = 3). The subjects included 13 men and seven women with a mean age of 54 years (34-74 years). Complaints were major and serious: pain (n = 20), rectal syndrome (n = 17), recto-vesical fistula (n = 5) recto-vaginal fistula (n = 5), urinary infection (n = 13), and hematuria (n = 6). Preoperative radiotherapy was performed in 11 patients and preoperative radio chemotherapy in six. The surgical procedure included a total pelvic exenteration with perinectomy in 12 patients, and a total pelvic exenteration with preservation of levator ani and perineum in eight, associated in two cases with a partial resection of the sacrum, and in two other cases with partial hepatectomy for a single liver metastasis. Urinary diversion was a trans ileal ureterostomy in 17 patients and a direct double ureterostomy in three.. The mean duration of surgery was 6 h. The mean preoperative blood loss was 1,200 L. Nine patients received blood transfusion. There was no postoperative mortality but in contrast, the morbidity rate was high with mainly urinary and digestive complications, pelvic sepsis and thromboembolic complications. After pathological examination, tumoral resections were classified R0 in 19 cases, and R1 in one. All tumors were T4 with tumoral invasion of the bladder (n = 15), prostate (n = 6), seminal vesicles (n = 4), ureter (n = 3), vagina (n = 7), urethra (n = 1), and sacrum (n = 1). Lymph node involvement was present in four patients. The 3 and 5 year actuarial survival rate was respectively 47 and 18%. Thirteen patients died of their cancer, nine from metastases, and four from local recurrence with a mean survival of 29 and 32 months respectively. Seven patients were alive at the time of this study, six without actual recurrence.. In spite of its aggressive aspect, total pelvic exenteration seems justified in rectal carcinoma when extended to the urinary tract, when it causes major functional disorders, when there are no detectable metastases, and when the tumor has no posterior or lateral fixation. Local tumoral evolution can usually be controlled by pelvic exenteration but prolongation of survival is not demonstrated.

Topics: Adenocarcinoma; Adult; Aged; Antidotes; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Pelvic Exenteration; Postoperative Complications; Preoperative Care; Radiotherapy Dosage; Rectal Neoplasms; Retrospective Studies; Time Factors

It is not yet known whether preoperative combined radiotherapy and chemotherapy for rectal cancer affects postoperative mortality and morbidity. We therefore evaluated early postoperative complications in patients given adjuvant radiotherapy and chemotherapy before surgery for middle and lower rectal adenocarcinoma.. Between 1994 and 1998, 41 patients underwent combined preoperative pelvic radiotherapy and chemotherapy at our institution. Most of the patients had 45 Gy (1.8 Gy/day/25 fractions) during five weeks plus 5-fluorouracil (350 mg/m2/day) and low-dose leucovorin (10 mg/m2/day) bolus on Days 1 to 5 and 29 to 33. Surgery was performed four to six weeks after completion of adjuvant therapy. The 41 patients (Group A) were retrospectively compared with 30 patients (Group B) who, in the same period, underwent surgery without preoperative adjuvant therapy. The groups were homogeneous for age, gender, preoperative risk factors, operating surgeon, and pathologic stage. Mean distance of the tumor from the anal verge was shorter in Group A patients (P = 0.031).. There were seven major postoperative complications in each group. No significant differences were found between the groups for morbidity and mortality rates. Considering all patients, more postoperative complications were found in patients scored as American Society of Anesthesiologists 3, in those with a preoperative hemoglobin value < 10 g/dl, and in those without a diverting stoma (P = 0.0048, P = 0.0453, and P = 0.0033, respectively). At multivariate analysis, independent predictors of major complications were American Society of Anesthesiologists score (relative risk, 343; P = 0.022), diverting stoma (relative risk, 159; P = 0.010), type of surgical procedure (relative risk, 38.9; P = 0.048), preoperative hemoglobin value (relative risk, 9.72; P = 0.061), and intraoperative blood loss (relative risk, 1; P = 0.027). In Group A patients, the absence of diverting stomas was associated with major postoperative complications (P = 0.0307), and independent predictors of major complications were American Society of Anesthesiologists score (relative risk, 56; P = 0.111) and absence of a diverting stoma (relative risk, 22.42; P = 0.222).. Early postoperative complications after resection for middle and lower rectal adenocarcinoma are affected by intraoperative and preoperative risk factors and absence diverting stomas, but not by preoperative adjuvant therapy.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Antineoplastic Agents; Carboplatin; Case-Control Studies; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Morbidity; Multivariate Analysis; Postoperative Complications; Preoperative Care; Radiotherapy, High-Energy; Rectal Neoplasms; Retrospective Studies; Risk Factors

To determine the maximum-tolerated dose (MTD) and recommended dose of irinotecan (CPT-11) in combination with fluorouracil (5-FU) and leucovorin (LV), using a biweekly LV5FU2 regimen and increasing doses of CPT-11, and to assess the efficacy of this combination in pretreated patients with colorectal cancer (CRC).. All patients had metastatic CRC and a World Health Organization performance status of 0 or 1. CPT-11 was administered over a 90-minute infusion every 2 weeks at a range of dose levels (100, 120, 150, 180, 200, 220, and 260 mg/m(2)). LV5FU2 was started 1 hour after the end of the biweekly CPT-11 infusion and was also administered on day 2.. Fifty-five patients were entered onto this trial; 549 cycles were administered. The MTD was not reached at 260 mg/m(2), and a dose level of 300 mg/m(2) was added. The MTD as defined in the protocol was not reached at this dose level either, but all patients had cycles delayed and/or required a dose reduction. This dose was deemed to be the MTD. To take into account both the toxicity of and compliance with the biweekly schedule, the recommended CPT-11 dose was established at 180 to 200 mg/m(2). Antitumor activity was observed at almost all dose levels, with an objective response rate of 22%. Median time to progression was 6.3 months and overall survival was 15 months.. The biweekly CPT-11/LV5FU2 combination is feasible and safe, without overlapping toxicity. CPT-11 at 180 to 200 mg/m(2) in combination with LV5FU2 has been selected as the recommended dose for further studies.

Topics: Adult; Aged; Antidotes; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Diarrhea; Drug Administration Schedule; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Neutropenia; Rectal Neoplasms

Facial metastasis from colorectal carcinoma is extremely rare. Only two cases have been reported in the literature. This is the first reported case of malar metastasis from colon carcinoma. The patient was a 64-year-old, white woman who underwent a low anterior resection for a nearly obstructive carcinoma at 20 cm. Her chest X-ray revealed lung metastases. Postoperatively she was treated with fluorouracil and leucovorin. Twenty months later, she presented with left facial edema, which progressively increased in size. CT scan and magnetic resonance imaging with gadolinium showed a large soft tissue mass centered about the left anterior zygomatic arch. The platysma muscle was displaced laterally, and the masseter muscle was involved. There was extension into the masticator space and bony involvement of the zygomatic arch. True-cut biopsy of the left cheek revealed metastatic adenocarcinoma. Histology was similar to that of the primary rectal adenocarcinoma. Metastasis to the malar region is extremely rare. It is a grave prognostic sign, as it is associated with advanced terminal disease. Because of the widespread metastases, only palliative treatment can be provided.

Topics: Adenocarcinoma; Antidotes; Antimetabolites, Antineoplastic; Colonic Neoplasms; Fatal Outcome; Female; Fluorouracil; Follow-Up Studies; Humans; Intestinal Obstruction; Leucovorin; Lung Neoplasms; Middle Aged; Palliative Care; Rectal Neoplasms; Skull Neoplasms; Zygoma

Fifteen patients with rectal adenocarcinoma were endoscopically biopsied and given short-term [5 fluorouracil (5FU) (600 mg/m2) and Ca-Folinate (60 mg/m2) for two days] cytostatic therapy. Seven days later the tumor was resected or a second biopsy was performed. Apoptotic and mitotic indices were determined in the tumor tissue before and after the short-term chemotherapy. The patients were treated thereafter with long-term, intermittent 5 FU administration and followed up clinically for 4-13 months. Three patients showed progression of the disease, twelve improved or showed no tumor progression. An increase of the apoptotic index and decrease of the mitotic index after the short-term cytostatic treatment were seen in the tumor tissue of responder cases. Non-responders showed increase or no change in mitotic activity, and decrease or no change in apoptotic activity. These findings suggest that apoptotic and mitotic response to short-term cytostatic therapy may be additional predictive factor in rectal adenocarcinoma.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Apoptosis; Carcinoembryonic Antigen; Female; Fluorouracil; Humans; In Situ Nick-End Labeling; Leucovorin; Male; Middle Aged; Mitosis; Neoplasm Staging; Predictive Value of Tests; Prognosis; Rectal Neoplasms

Additional hyperthermia is able to intensify the effect of radio-chemotherapy in locally advanced rectal cancer. The datas represents favourable locally effect, if the necessary parameters of thermometry are achieved. We could demonstrate a correlation between temperatures and downstaging of the primary tumor. Consequently, aim of further developments is to optimize hyperthermia technology.

Topics: Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Administration Schedule; Fluorouracil; Follow-Up Studies; Humans; Hyperthermia, Induced; Leucovorin; Neoadjuvant Therapy; Neoplasm Staging; Rectal Neoplasms; Rectum; Thermometers; Treatment Outcome

Between January 1994 and November 1995, 41 patients with metastatic colorectal carcinoma were enrolled in this study. All these patients had recurrent disease after a prior 5-fluorouracil based adjuvant chemotherapy or failed to achieve response by prior chemotherapy that included 5-fluorouracil. 5-Fluorouracil, 2600 mg/m2, was administered concurrently with 100 mg/m2 leucovorin over 24 hours of continuous intravenous infusion. The treatment was repeated every week until progressive disease was documented. Forty-one patients received a total of 810 courses of treatment. The overall response rate was 17.1% (95% confidence interval 5.6-28.6%). In two patients who achieved complete response, the liver was the metastatic site. The median survival was 18.4 months for responders and 12.6 months for non-responders. Gastrointestinal toxicities including diarrhea, stomatitis, nausea and vomiting were the major side-effects. Sixteen incidences (39.0%) of grade 2-3 gastrointestinal toxicities were observed. One patient (2.4%) developed a grade 3 cardiac toxicity, and another one (2.4%) had a grade 2 neurotoxicity. Hematological toxicities were minimal with no evidence of severe (grade 2 or more) leukopenia or thrombocytopenia. We conclude that in patients with pretreated metastatic colorectal cancer, weekly 24-hour infusion of high-dose 5-fluorouracil and leucovorin is associated with higher efficacy and tolerable toxicity. This regimen is a good option as a second-line treatment for those whose diseases are recurrent from or refractory to prior 5-fluorouracil, and deserves a longer period of follow-up.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Rectal Neoplasms; Survival Analysis

A 37-year-old man was diagnosed as having a rectal cancer with familial adenomatous polyposis, with the mutation of APC gene, and gastric polyposis, hypertrophy of the retinal pigment epithelium and a lipoma of the left arm. The patient underwent a total colectomy for the rectal cancer and a partial resection of the liver for metastasis (S3) which was detected on laparotomy, followed by cannulation in the hepatic artery. After the operation, 5-FU alone and low doses of CDDP and 5-FU were administered, but the level of serum CEA elevated and CT scanning showed multiple liver metastases. Then, low doses of leucovorin (30 mg/body bolus) and 5-FU (500 mg/body/h) were injected through an injection port every week. After 6 months, the level of serum CEA reduced and CT scanning showed minor response (about 30% on the decrease rate), without side effects, including diarrhea, stomatitis and bone marrow suppression.

Topics: Adenomatous Polyposis Coli; Adult; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Fluorouracil; Genes, APC; Hepatic Artery; Humans; Infusion Pumps, Implantable; Leucovorin; Liver Neoplasms; Male; Rectal Neoplasms

The objective of this prospective study was to determine the possibility of treatment based exclusively on chemotherapy and radiotherapy for patients with low infiltrative rectal tumors in an attempt to preserve sphincter function.. Sixteen patients with rectal adenocarcinoma up to 3 cm above the pectineal line with initial indications for abdominoperineal resection (APR) were submitted to a 5040-cGy (28 x 180 cGy) radiotherapy dose and chemotherapy during the first 3 and last 3 days of radiotherapy, using 425 mg/m2/day of 5-fluorouracil (5FU) and 20 mg/m2/day of folinic acid. Levamisole was used at 150 mg/day for 3 consecutive days at 2-week intervals throughout the period of therapy. Patients with a complete response were not submitted to APR, but received additional brachytherapy for curative purposes with doses from 2000 to 3000 cGy. Patients with recurrence after a complete response, with partial response, or with no response were submitted to APR.. Six patients (37.5%) presented a complete response, five (31.25%) presented a partial response, and five (31.35%) did not respond. The disease-free interval ranged from 1 to 34 months (mean = 11 months) among the six patients with complete response, and only one patient not submitted to APR is currently asymptomatic. Among the 15 patients with an indication for APR, three refused surgery because of full improvement of clinical symptoms and currently have tumor activity in the rectum. Mean patient follow-up was 23.8 months (8 to 43 months), and ten patients (62.5%) showed no evidence of active disease at last follow-up.. The therapeutic schedule used was not effective in preserving sphincter function in patients with low infiltrative rectal adenocarcinoma, because responses, although very frequent, were only temporary.

Topics: Abdomen; Adenocarcinoma; Adjuvants, Immunologic; Anal Canal; Antidotes; Antimetabolites, Antineoplastic; Brachytherapy; Cesium Radioisotopes; Disease-Free Survival; Female; Fluorouracil; Follow-Up Studies; Humans; Iridium Radioisotopes; Leucovorin; Levamisole; Male; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Peritoneum; Prospective Studies; Radiopharmaceuticals; Radiotherapy Dosage; Rectal Neoplasms; Remission Induction; Survival Rate; Treatment Outcome; Treatment Refusal

The authors analyzed the histological effect of preoperative chemotherapy for 41 colorectal advanced cancer patients using resected specimens. Twenty patients in the UFT + LV group received 400 mg/day of UFT and 30 mg/day of leucovorin for 10-14 days just before the operations. Twenty-one patients with UFT alone received UFT 400 mg/day during the same period. Only one patient in the UFT + LV group developed the side effect of mild leukocytopenia. The histological effect of the UFT + LV group was superior to that of the UFT alone group (p = 0.03). The number of Grade 1a and 1b in the UFT + LV group was 14 (60.9%) and 7 (30.4%), while in the UFT group 16 (66.7%) and 2 (8.3%). Histological examination revealed no lesions which showed Grade 2 and 3 in both groups. There was the tendency for the histological effect in moderately differentiated adenocarcinomas to be superior to that in well-differentiated adenocarcinomas in both group. The histological effect in metastatic lymph nodes was superior to that in the original colorectal lesions in both groups. This suggests preoperative chemotherapy with UFT + LV and UFT could achieve the clinical down-staging of advanced colorectal cancer.

Topics: Administration, Oral; Aged; Antidotes; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Drug Administration Schedule; Drug Combinations; Female; Humans; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Rectal Neoplasms; Tablets; Tegafur; Uracil

Colorectal adenocarcinoma is a major cause of cancer-related morbidity and mortality in Belgium and in other western countries. Prevention implies a modification of alimentation and maybe a chronic uptake of acetylsalicylic acid. Treatment of colorectal cancers is based on surgery and the prognosis is determined by the locoregional or metastatic tumor spread. Complete resection of any Astler Coller stage C colorectal malignant tumor has to be followed by a 5-fluorouracil-based adjuvant chemotherapy. In these protocols, 5-fluorouracil is administered together with folinic acid or levamisole. The administration of an adjuvant chemotherapy could also be considered for stage BII diseases. As rectal cancers are characterized by high local relapse rates, their treatment should associate radiotherapy, given either post-surgery or preferentially pre-surgery, with resection and chemotherapy. Appropriate treatment of colorectal cancers thus requires a concerted multidisciplinary approach.

Topics: Adenocarcinoma; Adjuvants, Immunologic; Anti-Inflammatory Agents, Non-Steroidal; Antidotes; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Aspirin; Belgium; Chemotherapy, Adjuvant; Colonic Neoplasms; Diet; Fluorouracil; Humans; Leucovorin; Levamisole; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Radiotherapy, Adjuvant; Rectal Neoplasms; Survival Rate

The aim of the study was to investigate the therapeutic value of reinduction therapy with the same cytostatic treatment that had been used for induction treatment in patients with metastatic colorectal cancer. A total of 71 patients, all of whom had responded or achieved stable disease lasting > or = 12 weeks after six monthly courses of first-line treatment with 5-fluorouracil + racemic leucovorin (5-FU/LV; n = 35) or 5-FU plus the l-isomer of LV (LLV; n = 34) were entered in this study. At the time of relapse, the same treatment was used for initial therapy: racemic LV or LLV was administered at 100 mg m(-2) day(-1) by i.v. bolus injection, immediately followed by 5-FU 400 mg m(-2) day(-1) given as a 2-h infusion. Chemotherapeutic drugs were given on 5 consecutive days at 4-week intervals x 6 or until there was evidence of tumour progression. Among 49 evaluable patients, reinduction therapy that was initiated after a median treatment-free interval of 5.4 months (range 3-14.5) resulted in nine partial response (PR) (18%) and 26 stable disease (SD) (53%), yielding an overall tumour control rate of 69% (95% confidence interval, 54.6-81.7%). The median time to treatment failure from reinduction was 6.4 months, and the median survival duration from reinduction was 8.9 months (20.1 months as judged from the beginning of induction therapy). The toxicity associated with retreatment was generally mild to moderate; compared with initial treatment, there was no significant difference in terms of the overall rate (P = 0.33) or severity (P = 0.19) of adverse reactions. Our data suggest that in patients with advanced colorectal cancer an interrupted treatment strategy, i.e. retreatment with the same regimen in case of relapse > or = 3 months after discontinuation of 6 months of successful treatment with 5-FU/LV or 5-FU/LLV is an acceptable therapeutic concept.

Topics: Adult; Aged; Antidotes; Antimetabolites, Antineoplastic; Colonic Neoplasms; Disease Progression; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Prospective Studies; Rectal Neoplasms; Recurrence; Remission Induction

The aim of this study was to evaluate the impact of combined radiotherapy and chemotherapy (leucovorin and 5-fluorouracil) on the treatment of potentially resectable low rectal cancer using the following end points: 1) toxicity of this combined modality regimen; 2) clinical and pathologic response rate and local control; 3) down-staging of the tumor and its influence on the number of sphincter-saving operations; 4) disease-free interval, patterns of relapse, and overall survival.. From 1991 to 1996, 118 patients with potentially resectable cases of histologically proven adenocarcinoma and no distant metastases were enrolled into this protocol. All patients were evaluated by clinical and proctologic examination, abdominal computed tomography, transrectal ultrasound, and chest radiography. Therapy consisted of 5,040 cGy (6 weeks) and concurrent leucovorin (20/mg/m2/day) with bolus doses of 5-fluorouracil administered intravenously at 425 mg/m2/day for three consecutive days on the first and last three days of radiation therapy. After two months, all patients underwent repeat evaluation and biopsy of any suspected residual lesions or scar tissue.. Median follow-up was 36 months. Toxicity of chemotherapy regimen was minimum. Thirty-six patients (30.5 percent) were classified as being complete responders. In six of these patients, complete response was confirmed by the absence of tumor in the surgical specimens (3 abdominoperineal resections and 3 proctosigmoidectomies with coloanal anastomosis). In the remaining 30 patients, confirmation of a complete response was made by the absence of symptoms, negative findings on physical examination, and biopsy, transrectal ultrasound, and pelvic computed tomographic test results during follow-up. Eighty-two patients (69.4 percent) were considered incomplete responders. Residual lesions had already been identified during the first examination in 74 patients. In the other eight patients, residual tumor was only identified after 3 to 14 months. All patients underwent surgical treatment, except one patient who refused surgery. Eighty-seven patients underwent 90 surgical procedures: local excision, 9; coloanal anastomosis, 36; abdominoperineal resection, 4; Hartmann's procedure, 1. Isolated local recurrences occurred in five patients (4.3 percent) and combined local and distant failure in eight patients (6.7 percent). Ninety patients are alive and disease-free at a median follow-up of 36 months.. Combined up-front chemoradiotherapy was associated with tolerable and acceptable side effects. A significant number of patients had complete disappearance of their tumors (30.5 percent) within a median follow-up of 36 months. This regimen spared 26.2 percent of patients from surgical treatment and allowed sphincter-saving management in 38.1 percent of patients who may have required abdominoperineal resection. Preliminary results of this trial suggests a reduction in the number of local recurrences and reinforces the concept that infiltrative low rectal cancer may be initially treated by chemoradiotherapy.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Anastomosis, Surgical; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Prospective Studies; Radiotherapy, Adjuvant; Rectal Neoplasms; Survival Analysis; Survival Rate; Treatment Outcome

Primary unresectable and locally advanced recurrent rectal cancer presents a significant clinical challenge. Local failure rates are high in both situations. Under such circumstances, there is a significant need to safely deliver tumoricidal doses of radiation in an attempt to improve local control. For this reason, we have incorporated a new approach utilizing high dose rate intraoperative radiation therapy (HDR-IORT).. Between 11/92-12/96, a total of 112 patients were explored, of which 68 patients were treated with HDR-IORT, and 66 are evaluable. The majority of the 44 patients were excluded for unresectable disease or for distant metastases which eluded preoperative imaging. There were 22 patients with primary unresectable disease, and 46 patients who presented with recurrent disease. The histology was adenocarcinoma in 64 patients, and squamous cell carcinoma in four patients. In general, the patients with primary unresectable disease received preoperative chemotherapy with 5-fluorouracil (5-FU) and leucovorin, and external beam irradiation to 4500-5040 cGy, followed by surgical resection and HDR-IORT (1000-2000 cGy). In general, the patients with recurrent disease were treated with surgical resection and HDR-IORT (1000-2000 cGy) alone. All surgical procedures were done in a dedicated operating room in the brachytherapy suite, so that HDR-IORT could be delivered using the Harrison-Anderson-Mick (HAM) applicator. The median follow-up is 17.5 months (1-48 mo).. In primary cases, the actuarial 2-year local control is 81%. For patients with negative margins, the local control was 92% vs. 38% for those with positive margins (p = 0.002). The 2-year actuarial disease-free survival was 69%; 77% for patients with negative margins vs. 38% for patients with positive margins (p = 0.03). For patients with recurrent disease, the 2-year actuarial local control rate was 63%. For patients with negative margins, it was 82%, while it was 19% for those with positive margins (p = 0.02). The disease-free survival was 47% (71% for negative margins and 0% for positive margins) (p = 0.04). Prospective data gathering indicated that significant complications occurred in approximately 38% of patients and were multifactorial in nature, and manageable to complete recovery.. HDR-IORT using our technique is versatile, safe, and effective. The local control rates for primary disease compare quite well with other published series, especially for patients with negative margins. For patients with recurrent disease, locoregional control and survival are especially encouraging in patients with negative resection margins. Further follow-up is needed to see whether these encouraging data will continue.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antidotes; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Combined Modality Therapy; Disease-Free Survival; Female; Fluorouracil; Humans; Intraoperative Period; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Radiotherapy Dosage; Rectal Neoplasms

The present "sandwich" preoperative and postoperative chemotherapy and radiation study was undertaken to evaluate the impact of treatment intensity on the local control and survival in tethered or fixed rectal adenocarcinoma (T3, 4 NX M0).. Between 1990 and 1992, 27 patients were treated with this sandwich protocol. Preoperative therapy consisted of 4 weeks of concurrent radiation (40 Gy) and chemotherapy (mitomycin C on day 1, 5-fluorouracil infusion and leucovorin on days 1-4 and days 15-18, respectively), and one cycle of bolus 5-fluorouracil and leucovorin chemotherapy. After surgery, they received 2 additional weeks of radiation (18 Gy) and 4 days of similar chemotherapy. The outcome was compared to another 54 patients who were treated with our previous preoperative chemoradiation protocol (mitomycin C, 5-fluorouracil infusion and 40 Gy of pelvic RT).. The complete resectability rate was improved from 91% in the preoperative protocol to 100% in the sandwich protocol, and the pathologic complete response rate (T0 N0 M0) was increased from 4 to 15%. There was no local recurrence in the sandwich protocol. The 4-year local failure rate was 23 vs. 0% (p = 0.005). The 4-year distant failure rate was 47 vs. 28% (p = 0.079). The 2-year and 4-year survival were 63 and 41% for the preoperative protocol, vs. 92 and 72% for the sandwich protocol, respectively (p = 0.014). There were more treatment-related Grade 2 diarrhea, but not Grade 3/4 diarrhea in the sandwich protocol. Two patients (7%) in the sandwich protocol developed late gastrointestinal complications.. More intensive radiation and chemotherapy appeared to improve the resectability, local control, and survival in tethered and fixed rectal cancers. There was a moderate but acceptable increase in the bowel morbidity.

Topics: Adenocarcinoma; Adult; Aged; Antidotes; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Mitomycin; Neoplasm Metastasis; Radiotherapy; Radiotherapy Dosage; Rectal Neoplasms

In spite of the high prevalence of cancer in the elderly, little information is available about the efficacy and toxicity of chemotherapy in elderly patients. In a previous study, the authors demonstrated that the combination of uracil and tegafur (UFT) with leucovorin (LV) was active and well tolerated in patients with advanced colorectal carcinoma (ACC). The objective of the current study was to determine the efficacy and toxicity of this regimen in elderly patients with ACC.. Thirty-eight unselected patients older than 70 years (median age, 74 years) with measurable ACC were included. All patients were evaluable for toxicity and response. The regimen consisted of intravenous LV 500 mg/m2 on Day 1, oral LV 15 mg every 12 hours on Days 2-14, and oral UFT 390 mg/m2 on Days 1-14. Treatment was repeated every 28 days for a minimum of 4 courses per patient.. Two hundred eighty-eight cycles of chemotherapy were delivered (median, 7 per patient). Two patients (5%) achieved a complete response and 9 (24%) a partial response, for an overall response rate of 29%. Toxicity was mild, without dose-limiting myelosuppression. Four patients (10%) experienced Grade 3-4 diarrhea, 1 patient had Grade 3-4 nausea/vomiting, and 1 had Grade 3-4 mucositis. Grade 3-4 toxicity was more frequent among women than men (38% vs. 4%, P < 0.05).. Treatment with oral UFT modulated with LV is effective, well tolerated, and feasible on an outpatient basis for elderly patients with ACC. However, elderly women should be followed closely for the early detection of toxicity.

Topics: Administration, Oral; Aged; Aged, 80 and over; Ambulatory Care; Antidotes; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Carcinoma; Clinical Protocols; Colonic Neoplasms; Diarrhea; Feasibility Studies; Female; Humans; Injections, Intravenous; Leucovorin; Male; Nausea; Rectal Neoplasms; Remission Induction; Sex Factors; Tegafur; Uracil; Vomiting

We report the downstaging, sphincter preservation, acute toxicity, and preliminary local control and survival results of preoperative 5-fluorouracil (5-FU), low-dose leucovorin (LV), and concurrent radiation therapy followed by postoperative LV/5-FU for treatment of patients with clinically resectable T3 rectal cancer.. A total of 32 patients received two monthly cycles of preoperative LV/5-FU (bolus daily X 5). Radiation therapy (5,040 cGy) began concurrently on day 1. Postoperatively, patients received a median of two monthly cycles of LV/5-FU (range, 0-10).. The complete response rate was 9 percent pathologic and 13 percent clinical, for a total of 22 percent. Total Grade 3+ acute toxicity during the preoperative combined modality segment was 25 percent (8/32). Of the 20 patients who were thought to initially require an abdominoperineal resection and for whom the intent of treatment was sphincter preservation, 17 (85 percent) were able to undergo sphincter-preserving surgery. With a median follow-up of 22 (3-59) months, none have developed local failure, and the three-year actuarial disease-free survival rate was 60 percent.. Our data reveal encouraging downstaging, sphincter preservation and acute toxicity with this regimen. Additional follow-up is needed to assess the long-term local control and survival rates.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Combined Modality Therapy; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Preoperative Care; Radiotherapy Dosage; Rectal Neoplasms

Two regimens of 5FU and folinic acid in the treatment of metastatic colorectal cancer were retrospectively analyzed. 33 patients received the high dose (HD) schedule (5FU 370 mg/m2 and Folinic Acid 200 mg/m2 i.v. on D1-5, every 4 weeks), 61 patients received the low dose (LD) schedule (5FU 400 mg/m2 and Folinic Acid 20 mg/m2 i.v. on D1-5, every 4 weeks). One patient in each group achieved a complete response, the overall response rate was 28% and 11% for the HD and LD groups, respectively. The median response duration was 183 days for the HD and 112 days for the LD group. The median survival duration was 387 days for the HD and 405 days for the LD group. The response rate and duration of response were higher in the HD group though this did not reach statistical significance. There was no difference in overall survival between the two patient groups. Neutropenia and gastro-intestinal symptoms were the most common toxicities, they were equal in both groups. One patient (3%) in the HD and 5 patients (9%) in LD group discontinued treatment due to toxicity. There were no treatment related deaths. It is concluded that low dose folinic acid in combination with 5FU is effective and produces similar toxicities as high dose folinic acid. It is concluded that low dose folinic acid in combination with 5FU is an effective alternative to high dose regimen in the palliative management of patients with metastatic colorectal cancer. However though it did not reach statistical significance the high dose regimen was associated with a higher response rate. This could have a significant effect when the combination is used in the adjuvant treatment of high risk patients.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colonic Neoplasms; Female; Fluorouracil; Humans; Intestines; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Neutropenia; Ontario; Palliative Care; Rectal Neoplasms; Remission Induction; Retrospective Studies; Stomach; Survival Rate

UFT. a a combination of tegafur and uracil, is increasingly used in the treatment of gastrointestinal malignancies. We report on a life-threatening toxicity observed in a 74-year-old female while undergoing adjuvant treatment with oral UFT plus leucovorm for adenocarcinoma of the rectum. The patient developed grade 4 thrombocytopenia, grade 4 neutropenia, grade 3 infection, grade 3 neurotoxicity and grade 2 cutaneous toxicity. This oral double-agent regimen should be used with caution in the adjuvant treatment of elderly patients with gastro-intestinal malignancies.

Topics: Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Female; Humans; Leucovorin; Rectal Neoplasms; Tegafur; Uracil

Three rectal cancer patients were treated with arterial infusion chemotherapy through the internal iliac artery. Two patients with pelvic recurrences unresectable after APRA were treated with intensive chemotherapy and the other patient with neoadjuvant chemotherapy. In all cases, 5-FU (500 mg/ body/day) was administered continuously for 5 days or 14 days. We attempted three methods for this procedure which were a bilateral catheterization to the internal iliac artery, a single catheterization with an embolization to the other internal iliac artery and a single catheterization without the embolization. As the result of this treatment, in the resected specimen with neoadjuvant case, histological necrosis was found in 50% in the main tumor and the metastatic lymph nodes. One patient with pelvic recurrence showed a partial response in CT imaging, but died one year later of the recurrence around the external iliac artery. The other patient with pelvic recurrence treated with the bilateral catheterization had no efficacy on CT imaging, but his CEA level has decreased at present. It was concluded that arterial infusion chemotherapy was effective for advanced rectal cancer and the pelvic recurrences. However, the efficacy of this treatment is limited to the area to which the drugs are delivered. Thus, it is important that the method and the location of the catheterization are determined adequately for each case.

Topics: Antidotes; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Administration Schedule; Fluorouracil; Humans; Iliac Artery; Infusions, Intra-Arterial; Leucovorin; Lymphatic Metastasis; Pelvic Neoplasms; Rectal Neoplasms

The case was a 43-year-old male who complained of anal bleeding and melena. He was diagnosed as rectal cancer with multiple liver metastases. Mile's operation with hepatic arterial cannulation was performed. This patient received 10 courses of arterial infusion chemotherapy using low-dose 5-FU, CDDP and LV. Tumor size of liver lesions significantly decreased. Internal iliac arterial cannulation was also performed for local recurrence. He received 3 courses of arterial infusion chemotherapy using the same regimen. The size of local recurrence also decreased. He had no side effect except mild epigastralgia and dermatitis around the stoma with good QOL.

Topics: Adult; Antidotes; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Fluorouracil; Hepatic Artery; Humans; Iliac Artery; Infusion Pumps, Implantable; Infusions, Intra-Arterial; Leucovorin; Liver Neoplasms; Male; Neoplasm Recurrence, Local; Rectal Neoplasms

Intra-arterial infusion chemotherapy combined with leucovorin (LV) and 5-fluorouracil (5-FU) was performed in two patients with multiple metastases from rectal and gastric cancer. In each patient LV 45 mg was infused as a bolus just before and after 5-FU 1,000 mg/4 hrs administration. Thereafter 5-FU dose was decreased gradually. This regimen was principally repeated weekly on an outpatient basis. In both patients PR was detectable 3 and 4 months after the beginning of chemotherapy, and CR was obtained in 21 and 6 months, respectively. Neither patient showed any signs of recurrence and are in good health 35 and 30 months after initiation of chemotherapy. These findings suggest that our protocol has an excellent anti-tumor effect and improves the QOL in some patients for a long time.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusion Pumps, Implantable; Infusions, Intra-Arterial; Leucovorin; Liver Neoplasms; Male; Middle Aged; Rectal Neoplasms; Remission Induction; Stomach Neoplasms

The use of 5-Fluorouracil and Leucovorin is recommended as palliative chemotherapy in metastatic colorectal cancer in patients under 75 years of age with symptomatic disease or objective progression of disease. However, the oncology units do not have the capacity to cope with this large group of patients and this presents a problem. The chemotherapy regime described is simple to use and can be administered by a general practitioner in cooperation with an oncology unit. Courses were held to inform general practitioners, surgeons and internists about the treatment. After an initial evaluation of the patient by an oncologist, treatment was given by the general practitioner according to written instructions. The treatment was evaluated jointly by the oncologist and the general practitioner. It is essential that the general practitioner should have easy access to advice from the oncology unit. It should be considered advantageous to the patient that the medical treatment be given as close to home as possible. This model for treatment will become increasingly important as more antitumour drugs, which can be administered by the general practitioner, become available.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Colonic Neoplasms; Drug Administration Schedule; Family Practice; Fluorouracil; Humans; Leucovorin; Models, Organizational; Norway; Oncology Service, Hospital; Palliative Care; Rectal Neoplasms

Topics: Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Fluorouracil; Humans; Leucovorin; Levamisole; Prognosis; Rectal Neoplasms

This study was undertaken to assess the accuracy and ability of endorectal ultrasound (ERUS) to predict changes in rectal tumor stage after a preoperative chemoradiation protocol.. Since December 1990, all rectal malignancies at our institution have been preoperatively staged with ERUS. ERUS has been an essential tool in preoperative staging of rectal cancer patients, possessing an overall accuracy of 84 percent for T stage and 81 percent for lymph node status in our hands (Williamson PR, unpublished data). Beginning in July 1992, all patients staged with T3 or T4 lesions on initial ERUS have been entered into a protocol consisting of preoperative chemoradiation therapy (CRT). This protocol consists of patients receiving 4,500 to 5,040 rads for five to eight weeks and concomitantly receiving sensitizing doses of 5-fluorouracil and/or leucovorin. All patients were scheduled for sphincter-saving or abdomino-perineal resections six to eight weeks following completion of CRT. A repeat ERUS was performed on each patient one week before surgery.. The study group consisted of 15 patients who completed CRT, including 12 males and 3 females. Evidence of tumor shrinkage via ERUS measurement was seen in all patients. Average tumor shrinkage as assessed by ERUS was 16 percent by width and 32 percent by depth of invasion. Sonographic level of invasion and nodal status were each downstaged in 38 percent of patients. Pathologic evaluation comparison revealed that the level of invasion was downstaged in 47 percent and nodal status in 88 percent compared with initial ERUS staging. Of those patients downstaged, 4 of 11 (36 percent) revealed no tumor in the pathology specimen.. We conclude from our early experience that although ERUS offers a method for assessing degree of shrinkage and downstaging of T3 and T4 lesions after CRT, presently it does not closely predict the pathologic results. Results are strongly related to the experience of the ultrasonographer. The ability to distinguish tumor from radiation-induced changes to perirectal tissues is under continued investigation, and a new method of interpreting the data obtained by ERUS after CRT will need to be established.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Neoplasm Staging; Preoperative Care; Radiation-Sensitizing Agents; Radiotherapy, Adjuvant; Rectal Neoplasms; Reproducibility of Results; Sensitivity and Specificity; Ultrasonography

This study examined a combined treatment for colorectal carcinoma, the dual biochemical modulation therapy, consisting of 5-FU, Leucovorin (LV) and Cisplatin (CDDP). We compared its anti-tumor effects with other treatments: 5-FU alone, CDDP alone and 5-FU with LV. Primary diffuse infiltrated colorectal carcinoma is well known for its biological malignancy and its lack of response to chemotherapy. We used SRM cells from a cell line of carcinoma of the rectum, and subcutaneously injected them into nude mice. The anti-tumor effects were estimated from the growth rate, inhibition rate and thymidylate synthetase inhibition rates in the tumor tissue. Results indicated that even if the concentration of 5-FU and LV were reduced by half, these combined with CDDP were more effective than other therapies. Dual biochemical modulation therapy is particularly promising because the reduction of the dosages would reduce the side effects while still serving as an excellent anti-tumor therapy.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Female; Fluorouracil; Humans; Immunologic Factors; Leucovorin; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Rectal Neoplasms

The authors report their 12 years of experience of intra arterial chemotherapy in pelvic recurrences and inoperable advanced stages of uterine carcinoma, rectal cancer and anal cancer. In squamous cell cancers the drug associations were mitomycin C, bleomycin, fluorouracil and folinic acid and cisplatin. In adenocarcinoma the same protocol contained no bleomycin. Drugs were infused for a 48 hours period in continuous infusion. The dosages were the same than in the intravenous regimens. Twenty patients with pelvic recurrences were included in this retrospective study: six were uterine cancers, fourteen were colo rectal cancers and two had advanced stage uterine cancer. Pain decreased in 10/14 patients with ano-rectal cancer pre sacral recurrence. Partial response was observed in 12 patients. Complete secondary surgical resection was possible in 4/14 rectal cancers and 6/6 uterine cancer recurrences. Chemotherapy induced a pathological complete response in 4/6 uterine cervix carcinoma recurrences. These observations led to perform pelvic intra arterial chemotherapy as first line treatment of locally-advanced inoperable pelvic tumors: 11 uterine cancers and five ano-rectal cancers. The objective were: tumor reduction before radiotherapy or surgery, tumor sterilization, decrease tumor volume for better radiation dosimetry, increase the chance of organ-preservation. The observation of tumor reduction in this small number of patients does not allow to draw definite conclusions. However the introduction of intra arterial pelvic chemotherapy as first line treatment of inoperable pelvic cancer warrants further studies.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Anus Neoplasms; Bleomycin; Cisplatin; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intra-Arterial; Leucovorin; Middle Aged; Mitomycin; Neoplasm Recurrence, Local; Rectal Neoplasms; Uterine Neoplasms

We report two cases of secondary myelodysplastic syndrome (SMDS) which followed successful treatment of a primary malignancy with high-dose chemotherapy supported by reinfusion of autologous stem cells. The SMDS was diagnosed 24 months and 40 months, respectively, following autografting. Both patients lived for 7 months after the diagnosis of SMDS. Our cases support the view that there is an increased risk of SMDS/acute leukemia following autologous marrow transplantation.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Marrow Transplantation; Combined Modality Therapy; Cyclophosphamide; Dose-Response Relationship, Drug; Doxorubicin; Etoposide; Humans; Leucovorin; Lymphoma; Male; Methotrexate; Myelodysplastic Syndromes; Prednisone; Procarbazine; Rectal Neoplasms; Risk Factors; Seminoma; Testicular Neoplasms; Transplantation, Autologous; Vincristine

51 patients with metastatic colorectal cancer (stage Dukes D) were treated with intravenous (i.v.) infusion on days 1, 3, 5, 8 and 16 with folinic acid (200 mg/m2) and 5-fluorouracil (600 mg/m2), and on days 1, 8 and 16 with cisplatinum (25 mg/m2 i.v.); cycles were repeated every 4 weeks. All 51 patients were evaluable for toxicity and response criteria. 26 patients had objective responses (3 complete responses, 5.9%; 23 partial responses, 45.1%), relative risk 51% (95% confidence intervals 36.7-65.0%). Response duration ranged from 4 to 28.0 months (median 16.8). Overall median survival of all patients included was 14.7 months (range 3.0-33.0). Toxicity of WHO grade III, requiring dose reduction, occurred in 9 (18%) patients. The regimen described here appears to be active, safe and well tolerated for treatment of patients with advanced colorectal cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Colonic Neoplasms; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Pilot Projects; Rectal Neoplasms; Time Factors; Treatment Outcome

Radiological and clinical evidence of acute necrosis in a meningioma following one cycle of chemotherapy with 5-fluorouracil, folinic acid, and levamisole was observed in a patient being treated for invasive rectal carcinoma. The possible mechanisms and implications of this occurrence are discussed.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Embolization, Therapeutic; Fluorouracil; Humans; Leucovorin; Levamisole; Male; Meningeal Neoplasms; Meningioma; Middle Aged; Necrosis; Neoplasms, Multiple Primary; Radiotherapy Dosage; Rectal Neoplasms

This study was undertaken to evaluate the treatment morbidity, functional outcome, and recurrence risk of patients undergoing local excision and combined chemoradiation therapy for rectal carcinoma.. Eighteen patients underwent local excision of their rectal carcinoma. Four patients underwent local excision alone (T1-2, N0-X, low risk), 10 patients underwent local excision with postoperative chemoradiation therapy using 5-fluorouracil and leucovorin (T1-2, N0-X, high risk), and 4 patients underwent local excision, chemoradiation therapy, and six months of additional 5-fluorouracil and leucovorin (T3 or N1).. Of the four patients undergoing local excision alone, there was no treatment morbidity or alteration in functional outcome. Of the 14 patients receiving chemoradiation therapy, three reported early Grade 3-4 toxicity manifested by cystitis, proctitis, or perineal skin desquamation. At six months, two patients reported persistent rectal urgency and occasional fecal incontinence, and 11 patients reported increasing stool frequency (average, 3: range, 2-8). The six months of additional 5-fluorouracil and leucovorin were well tolerated and did not appear to further affect functional outcome. There were no local recurrences, although one patient developed distant metastatic disease.. This treatment regimen, while generally well tolerated, is associated with significant acute toxicity in certain patients. We have identified specific causative factors which can be modified to decrease acute morbidity, including the elimination of leucovorin during the combined chemoradiation therapy.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Morbidity; Neoplasm Invasiveness; Neoplasm Staging; Postoperative Care; Prospective Studies; Rectal Neoplasms; Surgical Procedures, Operative; Time Factors; Tomography, X-Ray Computed; Treatment Outcome

Phase II studies involving novel chemotherapy treatment are often first reported to the scientific community as a published abstract. This study was designed to determine how authors report their phase II abstract data and what types of conclusions are made. All 1992 phase II colorectal cancer abstracts from the 1992 Proceedings of the American Society of Clinical Oncology were reviewed and analyzed for descriptive and quantitative data and conclusions. The response rate was the most commonly reported response statistic (28/29), with few studies reporting confidence intervals (4/29), median duration of response (5/29), or median survival (9/29). Toxicity data was quantitative in 21 trials and qualitative or absent in 8 trials. Conclusions about the toxicity data were ambiguous or absent in five trials. Conclusions about the response data included inappropriate use of terms, indirect or ambiguous language, or no conclusion. These results indicate that the reporting of phase II trials in abstract form is highly variable and plagued by problems that make data interpretation difficult. Recommendations for change are suggested.

Topics: Abstracting and Indexing; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Clinical Protocols; Clinical Trials, Phase II as Topic; Colonic Neoplasms; Communication; Fluorouracil; Humans; Interferons; Leucovorin; Rectal Neoplasms; Remission Induction; Research; Research Design

A reservoir system was implanted via the inferior epigastric artery into the internal iliac artery for local recurrence of rectal cancer under lumbar anesthesia. At the same time, the internal iliac artery on the opposite side of the tumor and the superior and inferior gluteal artery on the tumor side were embolized by gelform and coil. Five-hour continuous intraarterial infusion of 1,000 mg/m2 of 5-FU with intravenous drip infusion of 20 mg/m2 of leucovorin and one shot intraarterial infusion of 50 mg/m2 of cisplatin were performed as the treatment. This technique allows easier insertion of the catheter than by the conventional method, elevates the anticancer drug levels in the pelvic cavity and prevents ulcer of the buttocks and perineum. The technique is considered an effective form of treatment for local recurrence of rectal cancer.

Topics: Aged; Cisplatin; Embolization, Therapeutic; Evaluation Studies as Topic; Female; Fluorouracil; Humans; Infusion Pumps, Implantable; Injections, Intra-Arterial; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Rectal Neoplasms

A prospective trial was conducted involving 16 patients with colorectal adenocarcinoma using a regimen of continuous-infusion octreotide acetate (Sandostatin [octreotide acetate], Sandoz, East Hanover, NJ for the treatment of severe diarrhea induced by the weekly schedule of 5-fluorouracil (5-FU) in combination with leucovorin who were refractory to opiate therapy.. Fifteen patients had tissue-documented metastatic colorectal adenocarcinoma. An additional patient was treated adjuvantly. Fifteen patients were treated with chemotherapy consisting of 5-FU and high-dose leucovorin. The octreotide acetate regimen used was a continuous infusion of 50 micrograms/h for 12 hours followed by 100 micrograms/h for 12 hours and subsequently 150 micrograms/h for 72 hours. All patients were previous failures of diphenoxylate atropine (Lomotil diphenoxalate], Searle, Chicago, IL) given 2.5 mg orally after each loose bowel movement, but no more than 20 mg in a 24-hour period. Opiate therapy was not continued beyond 48 hours. All patients also were treated with bowel rest (nothing by mouth) and intravenous fluid hydration as well as octreotide acetate.. Complete resolution of diarrhea was seen in 15 of 16 patients (94%). In 4 patients this was accomplished during the 100 micrograms/h infusion, and in 11 patients during the 150 micrograms/h infusion. Recurrence of diarrhea was seen in two patients after a complete cycle of octreotide acetate. Both patients were restarted at 150 micrograms/h for 72 hours of octreotide acetate with resolution of the diarrhea within 36 hours of the infusion. No toxicity related to octreotide acetate was seen in this trial.. The continuous-infusion regimen of octreotide acetate 150 micrograms/h is an effective and safe schedule for the treatment of chemotherapy-induced diarrhea together with bowel rest and intravenous fluid hydration in a group of patients in whom the majority were treated with the weekly schedule of 5-FU and high-dose leucovorin.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Diarrhea; Female; Fluid Therapy; Fluorouracil; Humans; Infusions, Intravenous; Intestines; Leucovorin; Male; Middle Aged; Octreotide; Prospective Studies; Rectal Neoplasms; Recurrence; Remission Induction; Time Factors

A patient with a radically resected rectosigmoid cancer underwent two liver resections for metachronous metastases. When a third hepatic recurrence was diagnosed, further surgery was considered technically impossible, and the patient was given chemotherapy with 5-fluorouracil and folinic acid. He went into complete remission, and seven and a half years after the resection for colorectal cancer no metastases in the liver can be shown by ultrasonography or CT scan. The patient has normal CEA, and is at work.

Topics: Adenocarcinoma; Combined Modality Therapy; Fluorouracil; Hepatectomy; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Prognosis; Rectal Neoplasms; Reoperation; Sigmoid Neoplasms

A new sequential chemotherapy consisting of intravenous (IV) administration of methotrexate (MTX) 50 mg/m2 followed by 3 equal IV doses of 5-fluorouracil (5-FU) 500 mg/m2 at 1.4 and 21 hrs. and a leucovorin rescue (15 mg/body/8 hr) from 24 hrs. after MTX for 3 days was applied every two weeks for the patients with advanced colo-rectal cancer. The effectiveness of this MTX/3-dose 5-FU regimen was compared retrospectively with that of the standard sequential regimen consisting of the IV administration of MTX 100 mg/m2 followed by a single IV dose of 5-FU 800 mg/m2 one hr. later and a leucovorin rescue (21 mg/body/6 hr) 24 hrs. later given every week, namely MTX/1-dose 5-FU regimen. Partial response was achieved in 7 (46.7%) of 15 evaluable patients with the MTX/3-dose 5-FU regimen and in 3 (13.6%) of 22 evaluable patients with the MTX/1-dose 5-FU regimen (p < 0.05). The median survival times were 13 and 9 months, respectively. There were no significant difference in the patient characteristics between the two groups, and the toxic effects were much lower in the MTX/3-dose 5-FU than in the MTX/1-dose 5-FU regimen. It is therefore, concluded that the MTX/3-dose 5-FU regimen is superior to the standard MTX/1-dose 5-FU regimen.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Methotrexate; Middle Aged; Rectal Neoplasms; Retrospective Studies; Survival Rate

Five studies presented at the 1992 ASCO meeting are analysed. Kligerman's study was designed to determine if pre-treatment with WR-2721 could protect normal tissues from the toxicities induced by radiation therapy (in 100 patients with advanced rectal cancer). This pre-treatment resulted in a 13% reduction of moderate and severe acute toxicity. No WR-2721 patient experienced moderate or severe late toxicities compared to five in the group without pre-treatment. The complete response rate was higher in the WR-2721 group and there was no major WR-2721 related toxicity. Minski studied the acute toxicity (during treatment and two weeks after) of combined pelvic radiation therapy, 5-FU and leucovorin when delivered pre-operatively (16 patients) versus post-operatively (25 patients) in patients with rectal cancer. The toxicity criteria were fatigue, diarrhea, tenesmus, bowel movements, dysuria and erythema. Grade 3+ toxicity was more important in the post-operative therapy group (48% versus 13%). Given this high incidence of grade 3+ toxicity future randomized trials should explore the pre-operative approach. The final report of the inter group study of 5-FU plus levamisole as adjuvant therapy for stage C colon cancer was made by Moertel. With a median follow-up time of 5.5 years, the 5-FU plus levamisole treatment has reduced the recurrence rate by 39%, the cancer related death rate by 32% and the overall death rate by 31%. Most of the recurrences occurred during the first two years. There was a decrease in the liver, great omentum, peritoneum and lung metastases, but there was no modification in loco-regional recurrence rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Amifostine; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Clinical Trials as Topic; Colonic Neoplasms; Combined Modality Therapy; Fluorouracil; Humans; Leucovorin; Levamisole; Rectal Neoplasms

Thirty-four patients with nonresectable adenocarcinoma of the rectum, defined as tumor fixation at digital examination, were examined with MR. All 34 patients had, according to MR imaging, perirectal tumor growth. In 23 (68%) of the patients, the tumor has reached an adjacent organ. Eight of these patients had disturbances of the MR characteristics in the adjacent organ which proved to be due to overgrowth, i.e., to tumor invasion into these structures. In the remaining 15 patients, without disturbed MR characteristics, 7 had tumor overgrowth at laparotomy. When there was a visible space between the tumor and adjacent organs, there was no sign of tumor overgrowth at laparotomy, except in one case. In 24 patients, examined both before and after combined irradiation and drug therapy, tumor regression was registered after treatment. MR imaging seems to be useful in the assessment of resectability and to evaluate preoperative anticancer treatment in patients with nonresectable rectal carcinoma.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Magnetic Resonance Imaging; Male; Methotrexate; Middle Aged; Neoplasm Invasiveness; Rectal Neoplasms

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Rectal Neoplasms

To determine if fluorouracil (5-FU) plus high-dose leucovorin (LV) enhances local response in patients receiving preoperative radiation therapy (RT) for adenocarcinoma of the rectum, we compared the degree of downstaging in patients receiving preoperative RT with or without chemotherapy.. For this comparison, three groups of patients who were treated with identical doses and techniques of preoperative pelvic RT (total dose of 5,040 cGy) were examined. Group 1 included 20 patients with unresectable disease who received combined RT and LV/5-FU. Group 2 included 11 patients with unresectable disease who received preoperative RT. Group 3 included 21 patients with invasive, resectable, primary disease who received preoperative RT.. Patients with unresectable disease who received LV/5-FU had a higher rate of pathologic complete response (20% v 0%) and a lower incidence of positive nodes (30% v 64%) compared with those who did not receive chemotherapy. Even when the most favorable group of patients was included (group 3), patients who received LV/5-FU still had a higher complete response rate (20% v 6%) and a lower incidence of positive nodes (30% v 53%) compared with those who received RT without LV/5-FU. Of those patients with initially unresectable disease, the resectability rate was higher in those who received LV/5-FU compared with those who did not receive LV/5-FU (90% v 64%). Patients who received LV/5-FU experienced slightly more grade 1 to 2 fatigue, stomatitis, nausea, and grade 3 diarrhea, tenesmus, and dysuria.. Despite the fact that patients who received chemotherapy (group 1) had more advanced disease compared with those with resectable disease (group 3), the addition of LV/5-FU increased the resectability and downstaging rates. The ultimate impact of a complete response as well as a decrease in the incidence of pelvic nodes on local control and survival remains to be determined. However, given the enhancement of down-staging in patients with unresectable rectal cancer, we are encouraged by the combined modality approach.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Rectal Neoplasms; Treatment Outcome

Topics: Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Rectal Neoplasms; Thymidylate Synthase

Topics: Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Combined Modality Therapy; Fluorouracil; Humans; Leucovorin; Rectal Neoplasms; Semustine; Vincristine

Twenty patients with primary or recurrent unresectable rectal cancer limited to the pelvis were entered on a Phase I trial of preoperative pelvic radiation therapy (RT) (5040 cGy) and two cycles of combined high-dose leucovorin (LV) and 5-fluorouracil (5-FU), followed by surgery and ten cycles of postoperative LV/5-FU (sequential). Maximum tolerated doses (MTD) were determined for preoperative combined LV/5-FU and RT and for postoperative sequential LV/5-FU. 5-FU was escalated 50 mg/m2 while the LV remained constant at 200 mg/m2. The initial doses of 5-FU were combined LV/5-FU and RT (200 mg/m2) and sequential LV/5-FU (325 mg/m2). The median follow-up time was 14 months. The resectability rate was 89%, and the pathologic complete response rate was 21%. The MTD for combined LV/5-FU and RT was 300 mg/m2; therefore, the recommended dose of 5-FU is 250 mg/m2. The recommended dose of 5-FU for sequential LV/5-FU is 375 mg/m2. The dose-limiting toxicities in this trial were diarrhea, tenesmus, increased bowel movements, dysuria, and myelosuppression. For the six patients who received 5-FU at the recommended dose level, the median low counts were leukocyte count, 3.7/microliters (range, 2.4 to 4.9/microliters); hemoglobin, 9.0 g/dl (range, 8.2 to 11.9 g/dl); and platelet count (X1000), 146/microliters (range, 89 to 182/microliters). The incidence rate of any Grade 3 toxicity was 17% (diarrhea and frequent bowel movements). The recommended doses of 5-FU used in this protocol were well tolerated. Because there was a long delay before optimal doses of 5-FU could be delivered, the authors do not recommend that high-dose LV be used in conjunction with combined 5-FU and RT with the treatment regimen as currently designed. However, because the resectability and complete response rates were higher than those previously reported for preoperative RT alone, the authors are encouraged by the combined technique approach. New trials are currently being undertaken to determine if the use of a low-dose LV regimen is more tolerable.

Topics: Antineoplastic Combined Chemotherapy Protocols; Brachytherapy; Combined Modality Therapy; Fluorouracil; Humans; Leucovorin; Preoperative Care; Radiotherapy Dosage; Rectal Neoplasms; Sigmoid Neoplasms

Despite great efforts chemotherapeutic results of metastatic colorectal cancer are still unsatisfactory. In general, single agent treatment with 5-fluorouracil is the standard. The combination of 5-fluorouracil and folinic acid, however, shows favorable preliminary results which can be expected to lead to a small progress in this area. During the last several years the treatment strategy of squamous cell cancer of the anus has changed profoundly. In most patients radical surgery with colostomy has become unnecessary. With combined simultaneous chemotherapy and radiotherapy about 80% of all patients can achieve long term disease free survival.

Topics: Algorithms; Antineoplastic Combined Chemotherapy Protocols; Anus Neoplasms; Colonic Neoplasms; Combined Modality Therapy; Fluorouracil; Humans; Leucovorin; Rectal Neoplasms

Twenty-one consecutive patients with primarily non-resectable adenocarcinoma of the rectum were treated with preoperative split-course radiotherapy (40 Gy) and simultaneous sequential methotrexate + 5-fluorouracil + leucovorin (MFL). An initial infusion of methotrexate (250 mg/m2) was followed in the 2nd hour by 5-FU--first a bolus injection (10 mg/kg) and then continuous infusion (35 mg/kg/24 h) for 72 h. Leucovorin rescue (15 mg every 6 h) was initiated 24 h after the initial injection. Radiotherapy (10 Gy) was given with two 2.0 Gy fractions on days 1 and 2, and one fraction on day 3. The toxicity of the treatment was mostly mild to moderate. Compared with a previous consecutive series comprising 38 patients who received preoperative irradiation (greater than or equal to 40 Gy) only, with a resectability rate of 34%, the 71% resectability rate with this treatment seems to be superior.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Radiotherapy, High-Energy; Rectal Neoplasms

Thirty-one evaluable patients with measurable advanced colorectal carcinoma were entered into a pilot study that used weekly fluorouracil (5-FU) at the dose of 600 mg/m2 by bolus infusion administered midway during a two-hour leucovorin calcium infusion of 500 mg/m2. This regimen was repeated weekly for six doses. Twenty-seven of these patients (87%) were considered to be refractory to prior 5-FU therapy and four (13%) were previously untreated. All 31 patients successfully completed at least one 6-week cycle of this regimen with acceptable toxicity. The combined complete (CR) and partial response (PR) rate was 45% with another 25% of patients remaining stable. The 95% confidence levels for the responding patients are 27.6% and 62.7%, respectively. The remaining 30% of the patients had all received prior 5-FU therapy and progressed. All of the responding patients and 80% of the patients with stable disease received two or more cycles of this regimen after a 3- to 4-week interval off therapy. The median time to disease progression was 16.1 months for responding patients and 6.7 months for those patients with stable disease. The median survival for the responders was 20.6 months and for those with stable disease 9.8 months. The median survival for the nonresponding patients was 3.9 months. Toxicity included diarrhea in 70% of patients, skin rash (erythema) in 10%, stomatitis in 15%, nausea and vomiting in 25%, and myelosuppression in 10%. This study confirms and extends previous observations that demonstrate the improved efficacy of 5-FU when used with high-dose leucovorin in advanced colorectal carcinoma.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Pilot Projects; Rectal Neoplasms; Time Factors

Twenty-two patients with disseminated adenocarcinoma of the large bowel received therapy with 5-fluorouracil 800-1000 mg/m2 as a 24 h infusion for 4 consecutive days with 60 mg/m2 intravenous folinic acid administered every 6 hours. Major responses were seen in 3 of 20 (15%) evaluable patients, for a median of 5 months. Mucositis was the major toxicity occurring in 80% of patients. Folinic acid resulted in an additional $960/m2 per therapeutic course without improvement of response rate or survival at this dose and schedule.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Drug Synergism; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Liver Neoplasms; Male; Middle Aged; Rectal Neoplasms

Twenty-three patients with advanced colorectal cancer were treated with folinic acid (200 mg/m2/day 1-5 IV bolus injection) and 5-fluorouracil (400 mg/m2/day 1-5 IV in 15 minutes) every 28 days. Only three patients were pretreated. Objective response was observed in 6 (30%) of 20 evaluable patients (three complete and three partial responses). The median duration of response was 9 months (range 5-15) and time to disease progression ranged from 2 to 12 months (median 6 months). Median survival was 21 months (range 12-23+) for responders. Another 6 (30%) patients had stabilization of disease. Toxicity was generally gastrointestinal (mucositis, diarrhea, nausea); moderate leukopenia was noted. The response rate found in this study indicates that folinic acid administered in high doses enhances the effectiveness of 5-FU administered concomitantly in colorectal cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Female; Fluorouracil; Gastrointestinal Diseases; Hematologic Diseases; Humans; Infusions, Intravenous; Injections, Intravenous; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Rectal Neoplasms

Plasma pharmacokinetics of high-dose (500 mg/m2) leucovorin calcium (dl-5-formyltetrahydrofolic acid [dl-CF]) and fluorouracil (FUra) have been evaluated in patients with advanced colorectal cancer treated with the combination of FUra and dl-CF by two different intravenous (IV) schedules: (A) In patients with no prior chemotherapy, dl-CF was administered by a two-hour IV infusion and FUra by rapid IV injection one hour after the start of the dl-CF infusion and (B) in previously treated patients, dl-CF and FUra were administered by five-day continuous IV infusion (CI). Following the two-hour infusion of dl-CF, mean peak plasma concentration and elimination half-life of I-5-formyltetrahydrofolic acid (I-CF) were 24 +/- 6 mumol/L and 0.8 +/- 0.1 hour, respectively. CI of dl-CF over five days yielded a mean steady-state plasma level of I-CF of only 1.2 +/- 0.5 mumol/L. Peak and steady-state plasma concentrations of the metabolite 5-methyl tetrahydrofolic acid were comparable in the two schedules (17 +/- 8 mumol/L for the two-hour infusion and 12 +/- 5 mumol/L for the CI). Areas under the concentration v time curve (AUC) of total reduced folates were significantly greater under conditions of CI: 89.0 v 16.7 mmol/L/min for the two-hour infusion. In tumor tissue, 5,10-methylenetetrahydrofolate increased eight-fold two to four hours following the two-hour infusion and two-fold during the CI of dl-CF and FUra. Inhibition of thymidylate synthase (dTMP-S) by the two-hour and CI infusion schedules were 66% v 39%, respectively. The observed differences in the intracellular dTMP-S folate cofactor pools and the degree of inhibition of dTMP-S achieved in patients treated by two different schedules may be due to differences in the biochemical properties and/or to differences in the modulation of FUra metabolism by folate of tumor tissues obtained from newly diagnosed and previously treated patients.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chromatography, High Pressure Liquid; Colonic Neoplasms; Fluorouracil; Half-Life; Humans; Infusions, Intravenous; Injections, Intravenous; Leucovorin; Rectal Neoplasms; Tetrahydrofolates

Topics: Adenocarcinoma; Animals; Bone Marrow; Colonic Neoplasms; Deoxyuracil Nucleotides; Fluorodeoxyuridylate; Fluorouracil; Humans; Intestinal Mucosa; Leucovorin; Liver; Pancreatic Neoplasms; Rats; Rats, Inbred Strains; Rectal Neoplasms; Stomach Neoplasms; Thymidylate Synthase

Thirteen patients with metastatic colorectal adenocarcinoma underwent treatment with continuous ambulatory 5-fluorouracil (5-FU) infusion 300 mg/m2/day and intermittent bolus methotrexate (MTX) (200 mg/m2) with calcium leucovorin (LCV) 10 mg/m2 orally every 6 h X four to eight doses given 24 h after MTX. Although MTX administration was planned every 14 days, the average time between treatments exceeded 19 days (range 14-42) because of excessive toxicity. All patients experienced toxicity at some time in their treatment course, requiring interruption of 5-FU infusion in 12 of 13 patients. Significant toxicities included stomatitis (13 of 13 patients), hand-foot syndrome (8 of 13 patients), and diarrhea (3 of 13 patients). Toxicity did not appear to be minimized by attenuation of MTX and/or 5-FU dosage or by increasing the dose and/or duration of LCV. At this dosage schedule the addition of MTX/LCV to 5-FU infusion results in excessive and unacceptable toxicity and does not appear to improve treatment results.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Drug Administration Schedule; Drug Evaluation; Drug Synergism; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Methotrexate; Middle Aged; Rectal Neoplasms

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Diarrhea; Fluorouracil; Humans; Leucovorin; Rectal Neoplasms

The therapeutic activity of 5-FU in large bowel cancer is enhanced by increasing the intracellular pool of reduced folates. We treated 45 patients with advanced colon cancer with HDFA and 5-FU for 5 consecutive days. None had been given previous radio- or chemotherapy. All had measurable disease. Not one complete response was observed. Thirteen of the 39 evaluable patients showed partial response. Median duration of response was 9+ months. The probability of 50% survival was 15 months for all evaluable patients. There was no case of severe toxicity and the principal toxic effects were oral mucositis and diarrhea. To date, HDFA + 5-FU is one of the most effective treatments for large bowel cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Diarrhea; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Mouth Mucosa; Rectal Neoplasms; Stomatitis

Forty-two patients with measurable advanced colorectal cancer were treated with sequential methotrexate (MTX) and 5-fluorouracil (5-FU), followed by folinic acid rescue. Twenty-one patients had received prior chemotherapy, mainly 5-FU (group 1) and remaining 21 patients had not been previously treated by cytotoxic agents (group 2). Two different treatment schedules were used. Regimen I (27 patients): MTX 250 mg/m2 was infused over 1 hour. Two hours from start 5-FU 600 mg/m2 was given as intravenous bolus. Folinic acid rescue started 24 hours after MTX infusion. Regimen II (15 patients): MTX 250 mg/m2 was given as 1-hour infusion. Three hours after the start of MTX a 46-hour 5-FU infusion (2000 mg/m2) was started. Folinic acid rescue as in regimen I. The chemotherapy courses were repeated every second week. After 3 cycles only one patient had partial response, 33 had no change and 8 progressive disease. The median time until progression was 2 1/2 months in group 1 and 4 months in group 2. The median survival was 7 months in group 1 and 10 1/2 months in group 2. Almost identical results were obtained by the two treatment schedules. The toxicity of both regimens was low.

Topics: Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Rectal Neoplasms; Time Factors

The data from an ongoing 3-arm prospective study of 72 patients with advanced colorectal carcinoma is presented. The 3 regimens are as follows: Regime 1 (every 4 weeks)--5-fluorouracil (FUra) (450 mg/m2 iv bolus daily for 5 days, then 200 mg/m2 iv bolus every other day for 6 doses); regime 2 (every week for 4 weeks, then every other week)--methotrexate (MTX) (50 mg/m2 in a 4-hour infusion) followed by FUra (600 mg/m2 iv bolus); regime 3 (weekly for 6 weeks followed by a 2-week rest period)--D,L-leucovorin (D,L-CF) (500 mg/m2 in a 2-hour infusion) with FUra (600 mg/m2 iv bolus) 1 hour after the D,L-CF infusion began. All monitoring lesions except lung were documented by tissue biopsy. Thirteen of 18 patients in the FUra + D,L-CF arm were evaluable for response. Six of the 13 patients (46%) have had a partial response. The duration of the 6 responses has been 11, 8, 7, 4, 3 and 3 months. In patients with liver metastases as the monitoring lesion, a dramatic improvement in liver function tests has been seen during the first 2 courses (12 weeks) of treatment, but this was not sustained. The toxicity of FUra + D,L-CF was predominantly gastrointestinal; unlike with FUra alone, myelosuppression was not predominant.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Colonic Neoplasms; Dose-Response Relationship, Drug; Drug Administration Schedule; Fluorouracil; Humans; Leucovorin; Rectal Neoplasms

We report the results of an expanded trial of 5-fluorouracil (FUra) combined with high-dose folinic acid for treatment of patients with advanced colorectal or gastric adenocarcinoma. In each treatment course, the patients received both FUra (340-400 mg/m2/day by iv infusion over 15 minutes) and folinic acid (200 mg/m2/day by iv bolus) for 5 consecutive days, with a 21-day interval between courses. Eighty-six patients with colorectal carcinoma were evaluated. The combined complete response (CR) and partial response (PR) rates were 39% for 54 patients who did not receive prior chemotherapy and 22% for 32 patients who had previously received chemotherapy. Four patients who were previously resistant to FUra attained objective responses. The median time to disease progression for the 28 responders was 10 months. The median survival time of responders was 19.5 months, and the probability of their being alive at 2 years was 40%. Of 27 patients with gastric adenocarcinoma, 13 (48%) responded to therapy. Their median time to disease progression was 5.5 months. The median survival time of responders was 11 months, and their probability of being alive at 15 months was 30%. Toxicity was within acceptable limits. Toxic effects included stomatitis, diarrhea, conjunctivitis, skin rash, and mild myeloid hypoplasia. In a separate study, plasma concentrations of L-folates above 10(-5) M were achieved after a rapid single iv injection of 200 mg/m2 of folinic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Fluorouracil; Gastrointestinal Neoplasms; Humans; Leucovorin; Metabolic Clearance Rate; Rectal Neoplasms; Stomach Neoplasms

Methotrexate (MTX) (250 mg/m2) was given as an i.v. infusion over 2 hr. At hour three and 23, 5-FU (500 mg/m2, maximally 1000 mg) was given as a bolus i.v. injection. The Leucovorin rescue was initiated hour 24. The chemotherapy course was repeated every 14 days for eight courses, then every third to fourth week. At least four courses of the regime were given to 50 patients with measurable advanced colorectal carcinoma. Toxicity was usually very mild but in seven patients an increase of serum creatinine was registered. Two of these patients had a severe period of uremia. With a more careful observation of kidney function, these episodes should have been foreseen. An objective response rate of 50% with six complete remissions (CR) and 19 partial remissions (PR) was found. Eighty-eight per cent (21/24) of the patients with tumour-related symptoms experienced symptomatic relief. The median response duration amounts to 5 months. It is concluded that the MFL regime is effective in inducing anti-tumour response in patients with advanced colorectal cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Neoplasm Metastasis; Rectal Neoplasms

Encouraging results have recently been reported for studies using folinic acid in combination with 5-fluorouracil (5-FU) in the treatment of patients with gastrointestinal (GI) malignancies. Thirty-six patients with advanced colorectal cancer with unequivocal evidence of progression while treated with fluoropyrimidines were treated with a six-day continuous infusion of 500 mg/m2/d of folinic acid initiated 24 hours before a five-day course of 5-FU administered as an intravenous (IV) bolus of 370 mg/m2/d. An initial dose of 250 mg/m2/d of 5-FU was used in patients previously treated with ionizing radiation and/or a nitrosourea. Three objective partial responses were observed. The overall median duration of survival was 8.1 months. Toxicity was acceptable and not in excess of that expected for 5-FU alone.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Drug Evaluation; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Nausea; Rectal Neoplasms; Stomatitis; Thrombocytopenia

Colorectal cancer is one of the most resistant tumors to chemotherapy. The efficacy of many kinds of anti-tumor drugs to the patients with colorectal cancer had been investigated, however most of the drugs was not effective or showed low response rates. As a few effective anti-tumor drug, 5-FU and its derivatives, nitrosoureas and mitomycin C were indicated. Response rates of combinations of these drugs were 20-30%. Methotrexate-5-FU with leucovorin therapy at proper administration intervals showed relatively high response rate to the patients. Effects of intra-arterial infusion of the drugs which often performed to the liver metastases were not so well as expected. Developments of new anti-tumor agents were essential.

Topics: Angiotensin II; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Combined Modality Therapy; Fluorouracil; Humans; Hyperthermia, Induced; Infusions, Intra-Arterial; Leucovorin; Methotrexate; Neoplasm Recurrence, Local; Rectal Neoplasms

Forty-four patients with locally recurrent or metastatic colorectal adenocarcinoma were treated with methotrexate (MTX) 100 mg/m2 i.v. followed 1 h later by 5-fluorouracil (5-FU) 600 mg/m2 i.v. Calcium leucovorin 10 mg/m2 p.o. q 6 h X four doses was given 24 h after MTX. The regimen was given on days 1 and 8 and repeated every 28 days. Six of 44 patients (14%) obtained either complete or partial response with a mean response duration of 6.8 months. Of 26 previously untreated patients there were one complete response (4%), four partial responses (15%), and 12 (46%) instances of stabilization of disease. Patients obtaining response or stabilization of disease experienced improved survival compared to those with progressive disease. Toxicity consisted of stomatitis and hematopoietic suppression requiring dose attenuation in six patients (14%); there were no treatment-related deaths. Sequenced MTX/5-FU is modestly active with acceptable toxicity in previously untreated patients with colorectal adenocarcinoma but offers no apparent advantage over single-agent 5-FU.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Rectal Neoplasms

Sixty-six patients with advanced colorectal adenocarcinoma and 24 with advanced gastric adenocarcinoma were treated; all had measurable tumors. The treatment was based on biochemical and cell culture studies which have demonstrated that an excess of intracellular reduced folates is necessary to provide optimal inhibition of thymidylate synthetase and to increase the cytotoxic effect of fluoropyrimidines. The treatment comprised 5-fluorouracil (5-FU) (370-400 mg/m2/day) and high dose folinic acid (200 mg/m2/day) given simultaneously for 5 consecutive days with a 21-day interval between courses. Of the 66 patients with colorectal carcinoma, 44 had not been previously treated with cytostatics and 22 were resistant to previous chemotherapy with 5-FU given either as a single agent or combined with other drugs. The response rates both complete (CR) and partial (PR) were 45% and 18% in the previously untreated and the previously treated patients, respectively. Time to disease progression in the 20 previously untreated patients ranged from 2 to 34.5+ months (median, 10.3 months) and that of the 4 patients previously resistant to 5-FU was 7, 10, 12 and 15 months, respectively. Median survival for the 24 responders was 20.4 months. Survival in responders was significantly superior to that observed in patients with progressive disease (P less than 10(-8)). Of the 24 patients with gastric adenocarcinoma, 23 had not been previously treated with cytostatics and one was resistant to a 5-FU containing regimen. The response rate (CR + PR) was 50% (12 patients). The single previously treated patient failed to respond. Time to disease progression in the 12 responders ranged from 2.1 to 28.9 months (median, 5.6 months).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenocarcinoma; Adult; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Rectal Neoplasms; Stomach Neoplasms

Attempts to modulate by normal metabolites the intracellular metabolism of 5-fluorouracil (FU) via the ribonucleotide pathway leading to increased incorporation of the drug into RNA have been shown to potentiate host toxicity but not the therapeutic efficacy of this agent in preclinical model systems and in patients with advanced colorectal carcinomas. Recent advances aimed at the modulation of FU metabolism by CF via the deoxyribonucleotide pathway leading to prolonged inhibition of dTMPS activity indicates that the therapeutic efficacy of FU can be enhanced significantly in patients with advanced colorectal carcinoma. Pharmacokinetic studies of FU and CF revealed large intrasubject variations. In this presentation, rationale and the results of approaches taken at the preclinical and clinical levels in an attempt to selectively modulate the therapeutic efficacy of fluoropyrimidine will be discussed. This includes the importance of integration of information concerning pharmacokinetics and cellular metabolism in the design of optimal combination chemotherapy of FU with metabolic modulators.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Fluorouracil; Humans; Kinetics; Leucovorin; Mice; Mice, Inbred BALB C; Rats; Rectal Neoplasms; Thymidine

Topics: Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Rectal Neoplasms

Twenty-six patients with metastatic colorectal adenocarcinoma were entered into a Phase I-II study of 5-fluorouracil (5-FUra)-high-dose leucovorin (CF). The starting dose of 5-FUra was 300 mg/sq m with escalation to 750 mg/sq m/week in 6 doses given by rapid i.v. injection midway during a 2-hr infusion of CF, 500 mg/sq m. Partial responses were seen in 9 of 23 patients (6 of 12 who had had previous 5-FUra). Complete normalization of liver enzymes was seen in two of these patients. Side effects were seen sporadically with 5-FUra doses up to 600 mg/sq m. At a 600-mg/sq m 5-FUra dose, 8 of 18 patients had diarrhea, and 2 of 18 had white blood cell counts less than 3000/microliter. At a 750-mg/sq m dose of 5-FUra, 6 of 11 patients had severe diarrhea and 6 of 11 had white blood cell counts less than 3000/microliter. Other toxicities were mild conjunctivitis and lacrimation, thinning of the nails, and alopecia. In bioavailability studies of CF p.o., no plasma CF could be detected. After CF i.v., mean plasma peak was 111.3 +/- 40.3 (S.D.) microM. 5-FUra-CF appears to be effective in patients clinically resistant to 5-FUra. This study is being extended to randomized trial of 5-FUra-CF versus 5-FUra alone.

Topics: Adult; Aged; Colonic Neoplasms; Drug Evaluation; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Rectal Neoplasms

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Fluorouracil; Humans; Leucovorin; Middle Aged; Rectal Neoplasms

We report the results of a therapeutic trial in patients with rectocolic and gastric metastatic adenocarcinomas. This trial is based on experimental evidence that an excess of reduced intracellular folic acid increases the cytotoxicity of fluoropyrimidines. The treatment consists of 5-fluorouracile (5-FU) (370 to 400 mg/m2/24 h) and folinic acid in high doses (200 mg/m2: 24 h) given simultaneously for 5 consecutive days; the interval between courses is 21 days. Thirty patients with measurable rectocolic adenocarcinomas were evaluated. They were divided into two groups: 16 patients had had no previous chemotherapy and 14 had not responded to chemotherapy with 5-FU alone or associated with other cytostatic drugs. Response rates were 56% in the first group and 21% in the second. Five patients with measurable gastric adenocarcinomas were also evaluated; none had received previous chemotherapy. A partial response was recorded in three of these patients. Toxicity of the therapeutic regimen was acceptable. Stomatitis was the most common toxic side-effect. In patients with severe adverse side-effects recurrence was efficiently prevented by decreasing the daily dose of 5-FU to 30 mg/m2 during subsequent courses. We conclude that in the tumors studied folinic acid in high doses can improve the antitumoral effect of 5-FU and induce a response to this agent in some rectocolic tumors which were previously resistant.

Topics: Adenocarcinoma; Adult; Aged; Colonic Neoplasms; Drug Therapy, Combination; Fluorouracil; Humans; Leucovorin; Middle Aged; Pilot Projects; Rectal Neoplasms; Stomach Neoplasms

Administration of methotrexate (MTX), 5-FU, and leucovorin rescue in 29 patients with metastatic colorectal cancer produced an objective response rate of 41.7%, with two complete remissions. Two patients developed fatal toxic effects and three others had severe toxic effects. This trial, however, supports the evidence for the synergistic effect of this drug combination.

Topics: Colonic Neoplasms; Drug Administration Schedule; Drug Therapy, Combination; Fluorouracil; Follow-Up Studies; Humans; Injections, Intravenous; Leucovorin; Methotrexate; Rectal Neoplasms

Topics: Adenocarcinoma; Adult; Aged; Colonic Neoplasms; Drug Evaluation; Female; Fluorouracil; Gastrointestinal Neoplasms; Humans; Leucovorin; Leukocyte Count; Male; Middle Aged; Pilot Projects; Platelet Count; Rectal Neoplasms; Stomach Neoplasms; Tomography, X-Ray Computed

In a phase II trial 24 patients with measurable metastatic colorectal carcinoma were treated every 2 weeks with high-dose metoprine at 175 mg/m2 and leucovorin rescue. Hematologic toxicity was mild; the limiting toxicity was CNS, occurring in 54% of the patients. No responses were observed, but four patients had disease stabilization. High-dose metoprine with leucovorin rescue appears ineffective in previously treated patients with colorectal carcinoma in the dose and schedule used in this study.

Topics: Adult; Aged; Antineoplastic Agents; Colonic Neoplasms; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Pyrimethamine; Rectal Neoplasms

Topics: Agranulocytosis; Antineoplastic Agents; Breast Neoplasms; Female; Hemangiosarcoma; Hodgkin Disease; Humans; Kidney Neoplasms; Leucovorin; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Lung Neoplasms; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Melanoma; Methotrexate; Osteosarcoma; Pancreatic Neoplasms; Radiography; Rectal Neoplasms; Rhabdomyosarcoma; Testicular Neoplasms; Thrombocytopenia