levoleucovorin and Peritoneal-Neoplasms

A rare appendiceal malignancy is characterized by both glandular and neuroendocrine histology. It often presents with dissemination of the perforated tumor to peritoneal surfaces. Current treatments involve systemic chemotherapy, cytoreductive surgery and perioperative intraperitoneal chemotherapy.. The impact of clinical, histological and treatment-related characteristics on survival were evaluated and subjected to univariate statistical analyses. All patients had stage IV disease and were treated by a uniform treatment strategy. Survival was determined from onset of disease until death or most recent follow-up.. There were 47 patients available for study of whom 17 were male. Median age was 48 with a range of 27-65. None or a single symptom vs. 2 or more symptoms had a significant effect on survival. Median survival of the entire cohort was 45 months and 34.88% and 8.72% of patients survived 5 and 10 years, respectively. The use of neoadjuvant chemotherapy showed no impact on survival. Patients with a peritoneal cancer index (PCI) of 0-20 as compared to PCI > 20 survived longer (p = 0.012). The survival of patients able to have a complete resection as compared to an incomplete resection of disease was significant (p = 0.0087). The type of perioperative chemotherapy did not alter survival.. These data show that patients with a lesser extent of disease with a complete cytoreduction had an improved prognosis. No benefit from systemic or perioperative regional chemotherapy was apparent. With long-term follow-up, patients with the combined glandular and neuroendocrine histology exhibiting peritoneal metastases have a guarded prognosis.

Topics: Adenocarcinoma; Administration, Intravenous; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Appendiceal Neoplasms; Carcinoid Tumor; Cytoreduction Surgical Procedures; Doxorubicin; Female; Fluorouracil; Humans; Hyperthermic Intraperitoneal Chemotherapy; Infusions, Parenteral; Leucovorin; Male; Middle Aged; Mitomycin; Neoadjuvant Therapy; Neoplasm Staging; Neoplasm, Residual; Neoplasms, Complex and Mixed; Neuroendocrine Tumors; Perioperative Period; Peritoneal Neoplasms; Prognosis; Survival Rate; Symptom Assessment

Topics: Adenocarcinoma, Mucinous; Antineoplastic Combined Chemotherapy Protocols; Cetuximab; Colonic Neoplasms; Combined Modality Therapy; Diagnosis, Differential; Female; Fluorouracil; Gallbladder; Genes, ras; Humans; Hyperthermia, Induced; Intestines; Leucovorin; Middle Aged; Neoadjuvant Therapy; Omentum; Organoplatinum Compounds; Ovarian Neoplasms; Peritoneal Neoplasms; Remission Induction; Round Ligaments; Second-Look Surgery

Topics: Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Camptothecin; Carboplatin; Combined Modality Therapy; Cystadenofibroma; Diagnosis, Differential; Female; Fluorouracil; Humans; Hyperthermia, Induced; Infusions, Parenteral; Irinotecan; Leucovorin; Mesothelioma; Middle Aged; Neoplasm Recurrence, Local; Neoplasms, Second Primary; Organoplatinum Compounds; Ovarian Neoplasms; Ovariectomy; Oxaliplatin; Paclitaxel; Pemetrexed; Peritoneal Neoplasms

Takotsubo syndrome (TTS)/cardiomyopathy is a syndrome that mimics acute myocardial infarction in the absence of coronary artery disease and is characterized by acute onset of chest pain, electrocardiographic abnormalities, and reversible left ventricular dysfunction. It is usually induced by emotional and physical stress. Fluorouracil is one of the most frequently used chemotherapy agents and a relatively common adverse reaction of fluorouracil is cardiotoxicity. Herein we describe a patient without a history of cardiovascular disorder who developed severe heart failure during infusion of fluorouracil for metastatic gastric cancer. Remarkably, the patient did not develop TTS during prior chemotherapy regimen, which also included fluorouracil. The patient's findings were consistent with the proposed TTS diagnostic criteria and coronary angiography was normal, without obstructive coronary artery disease. With supportive care, the patient's cardiac functions returned to normal. TTS is not a well known syndrome to clinicians and this condition appears to occur more frequently than previously thought. In addition to the presented case, a review of the clinical features and outcome of 10 reported cases of fluorouracil-induced TTS is presented.

Topics: Amiodarone; Anti-Arrhythmia Agents; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Combined Modality Therapy; Coronary Angiography; Diagnostic Errors; Docetaxel; Electric Countershock; Fatal Outcome; Fluorouracil; Gastrectomy; Humans; Irinotecan; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Myocardial Infarction; Peritoneal Neoplasms; Peritonitis; Stomach Neoplasms; Takotsubo Cardiomyopathy; Taxoids; Ventricular Fibrillation

Metastatic colorectal cancer has evolved from a paradigm that was previously centered upon the use of systemic chemotherapy to one of multimodality therapy. Hepatectomy, pulmonary metastasectomy, and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy are surgical procedures that are now routinely performed in specialized institutions treating patients with metastatic colorectal cancer. Emerging evidence suggests that in selected patients, these procedures are safe and may be beneficial in contributing to long-term survival.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Clinical Trials as Topic; Colorectal Neoplasms; Combined Modality Therapy; Fluorouracil; Hepatectomy; Humans; Hyperthermia, Induced; Infusions, Parenteral; Leucovorin; Liver Neoplasms; Lung Neoplasms; Organoplatinum Compounds; Peritoneal Neoplasms; Pneumonectomy

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma; Clinical Trials as Topic; Colorectal Neoplasms; Combined Modality Therapy; Fluorouracil; Humans; Irinotecan; Leucovorin; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms; Treatment Outcome

To review the literature with regard to the incidence and prognostic significance of peritoneal seeding during surgery for primary colorectal cancer (CRC), the incidence of intraperitoneal recurrence of CRC, and the current treatment strategies of established PC of colorectal origin, with special focus on cytoreductive surgery and intraperitoneal chemotherapy (IPEC).. Although hematogenous dissemination forms the greatest threat to patients with CRC, peritoneal carcinomatosis (PC), presumably arising from intraperitoneal seeding of cancer cells, is a relatively frequent event in patients with recurrent CRC.. The PubMed and Medline literature databases were searched for pertinent publications regarding the incidence and prognostic significance of exfoliated tumor cells in the peritoneal cavity during curative surgery for primary CRC, the incidence of intraperitoneal recurrence of CRC, and the therapeutic results of systemic chemotherapy or cytoreductive surgery followed by IPEC.. The incidence of peritoneal seeding during potentially curative surgery for primary CRC, as reported in 12 patient series, varied widely, from 3% to 28%, which may be explained by differences in methods to detect tumor cells. PC is encountered in approximately 7% of patients at primary surgery, in approximately 4% to 19% of patients during follow-up after curative surgery, in up to 44% of patients with recurrent CRC who require relaparotomy, and in 40% to 80% of patients who succumb to CRC. The reported median survival after systemic 5-fluorouracil-based chemotherapy for PC varies from 5.2 to 12.6 months. Median survival after aggressive cytoreductive surgery followed by (hyperthermic) IPEC in selected patients, as reported in 16 patient series, tends to be better and varies from 12 to 32 months at the cost of morbidity and mortality rates of 14% to 55% and 0% to 19%, respectively. One randomized controlled trial has been published confirming the superiority of aggressive surgical cytoreduction and intraperitoneal chemotherapy over strictly palliative treatment.. Peritoneal seeding of cancer cells possibly leading to PC is a rather common phenomenon in patients with CRC. Cytoreductive surgery and adjuvant (hyperthermic) IPEC have been shown to be efficacious in selected patients and should therefore be considered in patients with resectable PC of colorectal origin.

Topics: Antineoplastic Agents; Carcinoma; Colorectal Neoplasms; Combined Modality Therapy; Fluorouracil; Humans; Incidence; Leucovorin; Neoplasm Seeding; Peritoneal Neoplasms; Postoperative Complications; Prognosis; Quality of Life; Survival Analysis

To date, no randomized clinical trials have investigated perioperative systemic therapy relative to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) alone for resectable colorectal peritoneal metastases (CPM).. To assess the feasibility and safety of perioperative systemic therapy in patients with resectable CPM and the response of CPM to neoadjuvant treatment.. An open-label, parallel-group phase 2 randomized clinical trial in all 9 Dutch tertiary centers for the surgical treatment of CPM enrolled participants between June 15, 2017, and January 9, 2019. Participants were patients with pathologically proven isolated resectable CPM who did not receive systemic therapy within 6 months before enrollment.. Randomization to perioperative systemic therapy or CRS-HIPEC alone. Perioperative systemic therapy comprised either four 3-week neoadjuvant and adjuvant cycles of CAPOX (capecitabine and oxaliplatin), six 2-week neoadjuvant and adjuvant cycles of FOLFOX (fluorouracil, leucovorin, and oxaliplatin), or six 2-week neoadjuvant cycles of FOLFIRI (fluorouracil, leucovorin, and irinotecan) and either four 3-week adjuvant cycles of capecitabine or six 2-week adjuvant cycles of fluorouracil with leucovorin. Bevacizumab was added to the first 3 (CAPOX) or 4 (FOLFOX/FOLFIRI) neoadjuvant cycles.. Proportions of macroscopic complete CRS-HIPEC and Clavien-Dindo grade 3 or higher postoperative morbidity. Key secondary outcomes were centrally assessed rates of objective radiologic and major pathologic response of CPM to neoadjuvant treatment. Analyses were done modified intention-to-treat in patients starting neoadjuvant treatment (experimental arm) or undergoing upfront surgery (control arm).. In 79 patients included in the analysis (43 [54%] men; mean [SD] age, 62 [10] years), experimental (n = 37) and control (n = 42) arms did not differ significantly regarding the proportions of macroscopic complete CRS-HIPEC (33 of 37 [89%] vs 36 of 42 [86%] patients; risk ratio, 1.04; 95% CI, 0.88-1.23; P = .74) and Clavien-Dindo grade 3 or higher postoperative morbidity (8 of 37 [22%] vs 14 of 42 [33%] patients; risk ratio, 0.65; 95% CI, 0.31-1.37; P = .25). No treatment-related deaths occurred. Objective radiologic and major pathologic response rates of CPM to neoadjuvant treatment were 28% (9 of 32 evaluable patients) and 38% (13 of 34 evaluable patients), respectively.. In this randomized phase 2 trial in patients diagnosed with resectable CPM, perioperative systemic therapy seemed feasible, safe, and able to induce response of CPM, justifying a phase 3 trial.. ClinicalTrials.gov Identifier: NCT02758951.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Capecitabine; Chemotherapy, Adjuvant; Colorectal Neoplasms; Cytoreduction Surgical Procedures; Feasibility Studies; Female; Fluorouracil; Humans; Hyperthermic Intraperitoneal Chemotherapy; Leucovorin; Male; Middle Aged; Mitomycin; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaliplatin; Perioperative Period; Peritoneal Neoplasms; Response Evaluation Criteria in Solid Tumors

Oral fluoropyrimidine plus cisplatin is often not tolerated by patients with severe peritoneal metastases of gastric cancer. Combination of 5-fluorouracil (5-FU), l-leucovorin (l-LV), and paclitaxel (FLTAX) has promising activity for such patients. We conducted a phase II/III study comparing FLTAX with 5-FU/l-LV.. Eligibility criteria included: unresectable or recurrent gastric adenocarcinoma; 20-75 years; performance status (PS) 0-2; peritoneal metastases + ; massive ascites and/or inadequate oral intake; no prior chemotherapy. Patients were randomly assigned to receive 5-FU/l-LV or FLTAX. The primary endpoint of phase III was overall survival: UMIN000010949.. We enrolled 101 patients. Early deaths occurred in patients with PS 2 having massive ascites and inadequate oral intake simultaneously; the protocol was amended to exclude such patients. Median survival times were 6.1 and 7.3 months for the 5-FU/l-LV and the FLTAX arms, respectively (HR 0.792; 80% CI 0.596-1.053; one-sided p = 0.1445). FLTAX arm had longer progression-free survival (PFS) [1.9 vs 5.4 months (HR 0.64; 95% CI, 0.43-0.96; p = 0.029)]. Grade 3/4 adverse events such as leucopenia and anorexia were more frequently observed in the 5-FU/l-LV arm. In the 5-FU/l-LV arm, two deaths were treatment-related. In the 5-FU/l-LV and FLTAX arms, 12 and 3 deaths occurred within 30 days after the last protocol treatment, respectively.. Chemotherapy was indicated for patients with severe peritoneal metastases excluding patients with PS 2 having massive ascites and inadequate oral intake simultaneously. FLTAX did not confer a significant survival benefit but may be preferred because of longer PFS and acceptable toxicity.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Paclitaxel; Peritoneal Neoplasms; Prognosis; Stomach Neoplasms; Survival Rate

Programmed cell death 1 (PD-1) inhibitors have limited effect in pancreatic ductal adenocarcinoma (PDAC), underscoring the need to co-target alternative pathways. CXC chemokine receptor 4 (CXCR4) blockade promotes T cell tumor infiltration and is synergistic with anti-PD-1 therapy in PDAC mouse models. We conducted a phase IIa, open-label, two-cohort study to assess the safety, efficacy and immunobiological effects of the CXCR4 antagonist BL-8040 (motixafortide) with pembrolizumab and chemotherapy in metastatic PDAC (NCT02826486). The primary outcome was objective response rate (ORR). Secondary outcomes were overall survival (OS), disease control rate (DCR) and safety. In cohort 1, 37 patients with chemotherapy-resistant disease received BL-8040 and pembrolizumab. The DCR was 34.5% in the evaluable population (modified intention to treat, mITT; N = 29), including nine patients (31%) with stable disease and one patient (3.4%) with partial response. Median OS (mOS) was 3.3 months in the ITT population. Notably, in patients receiving study drugs as second-line therapy, the mOS was 7.5 months. BL-8040 increased CD8

Topics: Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; CD8-Positive T-Lymphocytes; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Lymphocytes, Tumor-Infiltrating; Male; Middle Aged; Myeloid-Derived Suppressor Cells; Pancreatic Neoplasms; Peptides; Peritoneal Neoplasms; Receptors, CXCR4; Retroperitoneal Neoplasms; Survival Rate; T-Lymphocytes, Regulatory; Treatment Outcome

Peritoneal carcinomatosis of colorectal cancer origin is associated with poor prognosis. With regard to ovarian, gastric, and pancreatic cancer, the safety and efficacy of intraperitoneal administration of paclitaxel (ip PTX) has been demonstrated. This drug can be administered easily and repeatedly through a catheter into the peritoneal cavity. In this phase I study, we evaluated the safety of ip PTX combined with 5-fluorouracil, folinic acid, oxaliplatin, and bevacizumab (mFOLFOX6-bevacizumab) or capecitabine, oxaliplatin, and bevacizumab (CapeOX-bevacizumab) for colorectal cancer with peritoneal metastasis.. Colorectal cancer patients with histologically confirmed peritoneal carcinomatosis were enrolled. After the implantation of a peritoneal access port, 20 mg/m. Among the six patients enrolled, three received the mFOLFOX6-bevacizumab plus ip PTX regimen and three received the CapeOX-bevacizumab plus ip PTX regimen. Dose-limiting toxicity was not observed. Overall, grade 3 adverse events, such as leukopenia and neutropenia, were observed in two of three patients (66.7%) for each chemotherapeutic regimen, but no grade 4 adverse events were observed. Moreover, adverse events associated with the peritoneal access port, such as infection or occlusion of the catheter, were not observed.. The adverse events of mFOLFOX6-bevacizumab or CapeOX-bevacizumab in combination with ip PTX were considered similar to those described in previous studies of oxaliplatin-based treatment alone. 1 year after the start of chemotherapy, the efficacy of ip PTX will be evaluated as a secondary outcome.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Capecitabine; Colorectal Neoplasms; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Oxaliplatin; Paclitaxel; Patient Safety; Peritoneal Neoplasms; Prognosis; Young Adult

Purpose Our previous phase I trial suggested feasibility of addition of leucovorin (LV) to S-1 and gemcitabine therapy in advanced pancreatic cancer. The aim of this phase II trial was to assess the efficacy and toxicity of gemcitabine, S-1 and LV (GSL) combination therapy for advanced pancreatic cancer. Methods Chemotherapy-naïve patients with histologically or cytologically proven advanced pancreatic cancer were enrolled. Gemcitabine was administered at a dose of 1000 mg/m2 by 30 min infusion on days 1, S-1 40 mg/m2 orally twice daily and LV 25 mg orally twice daily on days 1 to 7 every 2 weeks. Primary end point was progression free survival (PFS). Results A total of 49 patients with advanced pancreatic cancer (19 locally advanced and 30 metastatic) were enrolled. Overall response rate and disease control rate were 32.7% and 87.8%. The median PFS and overall survival (OS) were 10.8 (95% confidence interval [CI], 7.4-13.5) and 20.7 (95% CI 13.0-NA) months with 1-year survival rate of 73.4%. Major Grade 3-4 toxicities were neutropenia (22.4%) and stomatitis (14.3%). No toxicity related death was observed. Conclusions In this single center, phase II trial, gemcitabine, S-1 and LV combination therapy was tolerable and can potentially be a treatment option for advanced pancreatic cancer.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Drug Combinations; Female; Follow-Up Studies; Gemcitabine; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Pancreatic Neoplasms; Peritoneal Neoplasms; Prognosis; Survival Rate; Tegafur

Purpose Few data described the activity of chemotherapy after ramucirumab plus paclitaxel progression in metastatic gastric cancer patients. The aim of this phase II study is to assess the efficacy and safety of the FOLFIRI regimen as a third-line of treatment. Methods The study enrolled patients with histologically proven metastatic gastric cancer or gastroesophageal junction carcinoma whose disease had progressed after ramucirumab-based second line of treatment. Treatment consisted of biweekly irinotecan 150 mg/m2 as a 1-h infusion on day 1, folinic acid 100 mg/m2 intravenously on days 1-2, and 5-fluorouracil as a 400 mg/m2 bolus and then 600 mg/m2 continuous infusion over 22 h on days 1-2. Primary end-point was tumor response rate (confirmed complete and partial response). Results Twenty-six patients were enrolled. Overall response rate and disease control rate were 11.5% and 38.5%. The median progression free survival (PFS) was 52 days (95% CI:42-74), and the median overall survival was 117 days (95% CI: 94-154). no unexpected adverse events have been observed. A longer PFS and OS were observed in patients who had achieved PFS ≥ 3 months during prior ramucirumab treatment. Conclusions Our findings suggest a poor efficacy of the FOLFIRI regimen in metastatic gastric or gastroesophageal junction cancer patients whose disease progressed during a ramucirumab-based second line of treatment. However, FOLFIRI could be an option for patients who responded to prior ramucirumab.

Topics: Adenocarcinoma; Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorouracil; Follow-Up Studies; Humans; Irinotecan; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Paclitaxel; Peritoneal Neoplasms; Prognosis; Ramucirumab; Stomach Neoplasms; Survival Rate

Upfront cytoreductive surgery with HIPEC (CRS-HIPEC) is the standard treatment for isolated resectable colorectal peritoneal metastases (PM) in the Netherlands. This study investigates whether addition of perioperative systemic therapy to CRS-HIPEC improves oncological outcomes.. This open-label, parallel-group, phase II-III, randomised, superiority study is performed in nine Dutch tertiary referral centres. Eligible patients are adults who have a good performance status, histologically or cytologically proven resectable PM of a colorectal adenocarcinoma, no systemic colorectal metastases, no systemic therapy for colorectal cancer within six months prior to enrolment, and no previous CRS-HIPEC. Eligible patients are randomised (1:1) to perioperative systemic therapy and CRS-HIPEC (experimental arm) or upfront CRS-HIPEC alone (control arm) by using central randomisation software with minimisation stratified by a peritoneal cancer index of 0-10 or 11-20, metachronous or synchronous PM, previous systemic therapy for colorectal cancer, and HIPEC with oxaliplatin or mitomycin C. At the treating physician's discretion, perioperative systemic therapy consists of either four 3-weekly neoadjuvant and adjuvant cycles of capecitabine with oxaliplatin (CAPOX), six 2-weekly neoadjuvant and adjuvant cycles of 5-fluorouracil/leucovorin with oxaliplatin (FOLFOX), or six 2-weekly neoadjuvant cycles of 5-fluorouracil/leucovorin with irinotecan (FOLFIRI) followed by four 3-weekly (capecitabine) or six 2-weekly (5-fluorouracil/leucovorin) adjuvant cycles of fluoropyrimidine monotherapy. Bevacizumab is added to the first three (CAPOX) or four (FOLFOX/FOLFIRI) neoadjuvant cycles. The first 80 patients are enrolled in a phase II study to explore the feasibility of accrual and the feasibility, safety, and tolerance of perioperative systemic therapy. If predefined criteria of feasibility and safety are met, the study continues as a phase III study with 3-year overall survival as primary endpoint. A total of 358 patients is needed to detect the hypothesised 15% increase in 3-year overall survival (control arm 50%; experimental arm 65%). Secondary endpoints are surgical characteristics, major postoperative morbidity, progression-free survival, disease-free survival, health-related quality of life, costs, major systemic therapy related toxicity, and objective radiological and histopathological response rates.. This is the first randomised study that prospectively compares oncological outcomes of perioperative systemic therapy and CRS-HIPEC with upfront CRS-HIPEC alone for isolated resectable colorectal PM.. Clinicaltrials.gov/ NCT02758951 , NTR/ NTR6301 , ISRCTN/ ISRCTN15977568 , EudraCT/ 2016-001865-99 .

Topics: Adult; Bevacizumab; Chemotherapy, Adjuvant; Colorectal Neoplasms; Combined Modality Therapy; Cytoreduction Surgical Procedures; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Oxaliplatin; Perioperative Period; Peritoneal Neoplasms; Peritoneum; Progression-Free Survival; Quality of Life

Epidemiologic and preclinical data suggest isoflavones have anticancer activity in colorectal malignancy prevention and treatment. This is the first clinical trial assessing safety and tolerability of Genistein in combination with chemotherapy in metastatic colorectal cancer.. Patients who had histologically confirmed metastatic colorectal cancer and had not received previous treatment were eligible to enroll. Subjects were treated with FOLFOX or FOLFOX-Bevacizumab as per the investigator choice. Genistein was administered orally for 7 days every 2 weeks, beginning 4 days prior to chemotherapy and continuing through days 1-3 of infusional chemotherapy. Primary endpoint was safety and secondary endpoints included cycle 6 response rate, best overall response rate (BOR), and median progression-free survival (PFS).. Thirteen patients received chemotherapy with Genistein in this trial. The most common adverse events related to Genistein alone were mild and included headaches, nausea, and hot flashes. One subject was observed to have grade 3 hypertension. No increase in chemotherapy-related adverse events was observed when Genistein was added. BOR and median PFS were 61.5% and 11.5 months, respectively.. We observed that adding Genistein to FOLFOX or FOLFOX-Bevacizumab was safe and tolerable. Efficacy results are notable and warrant verification in larger clinical trials.. The study was registered at ClinicalTrials.gov Identifier: NCT01985763.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Bone Neoplasms; Colorectal Neoplasms; Female; Fluorouracil; Follow-Up Studies; Genistein; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Oxaliplatin; Peritoneal Neoplasms; Pilot Projects; Prognosis; Survival Rate

Peritoneal carcinomatosis (PC) represents an unfavourable prognostic factor for patients with gastric cancer (GC). Intraperitoneal treatment with the bispecific and trifunctional antibody catumaxomab (EpCAM, CD3), in addition to systemic chemotherapy, could improve elimination of PC.. This prospective, randomised, phase II study investigated the efficacy of catumaxomab followed by chemotherapy (arm A, 5-fluorouracil, leucovorin, oxaliplatin, docetaxel, FLOT) or FLOT alone (arm B) in patients with GC and PC. Primary endpoint was the rate of macroscopic complete remission (mCR) of PC at the time of second diagnostic laparoscopy/laparotomy prior to optional surgery.. Median follow-up was 52 months. Out of 35 patients screened, 15 were allocated to arm A and 16 to arm B. mCR rate was 27% in arm A and 19% in arm B (p = 0.69). Severe side effects associated with catumaxomab were nausea, infection, abdominal pain, and elevated liver enzymes. Median progression-free (6.7 vs. 5.4 months, p = 0.71) and overall survival (13.2 vs. 13.0 months, p = 0.97) were not significantly different in both treatment arms.. Addition of catumaxomab to systemic chemotherapy was feasible and tolerable in advanced GC. Although the primary endpoint could not be demonstrated, results are promising for future investigations integrating intraperitoneal immunotherapy into a multimodal treatment strategy.

Topics: Adult; Aged; Antibodies, Bispecific; Antineoplastic Combined Chemotherapy Protocols; CD3 Complex; Docetaxel; Epithelial Cell Adhesion Molecule; Female; Fluorouracil; Gastrectomy; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Oxaliplatin; Peritoneal Neoplasms; Stomach Neoplasms

Surgical resection has a potential benefit for patients with metastatic adenocarcinoma of the stomach and gastroesophageal junction.. To evaluate outcome in patients with limited metastatic disease who receive chemotherapy first and proceed to surgical resection.. The AIO-FLOT3 (Arbeitsgemeinschaft Internistische Onkologie-fluorouracil, leucovorin, oxaliplatin, and docetaxel) trial is a prospective, phase 2 trial of 252 patients with resectable or metastatic gastric or gastroesophageal junction adenocarcinoma. Patients were enrolled from 52 cancer care centers in Germany between February 1, 2009, and January 31, 2010, and stratified to 1 of 3 groups: resectable (arm A), limited metastatic (arm B), or extensive metastatic (arm C). Data cutoff was January 2012, and the analysis was performed in March 2013.. Patients in arm A received 4 preoperative cycles of fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) followed by surgery and 4 postoperative cycles. Patients in arm B received at least 4 cycles of neoadjuvant FLOT and proceeded to surgical resection if restaging (using computed tomography and magnetic resonance imaging) showed a chance of margin-free (R0) resection of the primary tumor and at least a macroscopic complete resection of the metastatic lesions. Patients in arm C were offered FLOT chemotherapy and surgery only if required for palliation. Patients received a median (range) of 8 (1-15) cycles of FLOT.. The primary end point was overall survival.. In total, 238 of 252 patients (94.4%) were eligible to participate. The median (range) age of participants was 66 (36-79) years in arm A (n = 51), 63 (28-79) years in arm B (n = 60), and 65 (23-83) years in arm C (n = 127). Patients in arm B (n = 60) had only retroperitoneal lymph node involvement (27 patients [45%]), liver involvement (11 [18.3%]), lung involvement (10 [16.7%]), localized peritoneal involvement (4 [6.7%]), or other (8 [13.3%]) incurable sites. Median overall survival was 22.9 months (95% CI, 16.5 to upper level not achieved) for arm B, compared with 10.7 months (95% CI, 9.1-12.8) for arm C (hazard ratio, 0.37; 95% CI, 0.25-0.55) (P < .001). The response rate for arm B was 60% (complete, 10%; partial, 50%), which is higher than the 43.3% for arm C. In arm B, 36 of 60 patients (60%) proceeded to surgery. The median overall survival was 31.3 months (95% CI, 18.9-upper level not achieved) for patients who proceeded to surgery and 15.9 months (95% CI, 7.1-22.9) for the other patients.. Patients with limited metastatic disease who received neoadjuvant chemotherapy and proceeded to surgery showed a favorable survival. The AIO-FLOT3 trial provides a rationale for further randomized clinical trials.. clinicaltrials.gov identifier: NCT00849615.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Docetaxel; Esophagogastric Junction; Fluorouracil; Gastrectomy; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Metastasectomy; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms; Prospective Studies; Stomach Neoplasms; Survival Rate; Taxoids; Young Adult

This randomized phase II study compared weekly administration of paclitaxel (wPTX) with the best available 5-fluorouracil (5-FU) regimen as second-line treatment for advanced gastric cancer patients with severe peritoneal metastasis refractory to fluoropyrimidine.. In the best available 5-FU arm, continuous infusion of 5-FU (800 mg/m(2)/day, days 1-5, every 4 weeks) was given to patients with prior chemotherapy including bolus 5-FU, and methotrexate and 5-FU sequential bolus injection (methotrexate at 100 mg/m(2) followed by bolus 5-FU at 600 mg/m(2) with leucovorin, weekly) was given to those who had previously received continuous infusion of 5-FU or oral administration of fluoropyrimidine. In the wPTX arm, paclitaxel (80 mg/m(2)) was administered on days 1, 8, and 15, every 4 weeks. This study adopted a screening design (one-sided α = 30 %) with the primary end point of overall survival.. One hundred patients were randomized to the 5-FU arm (n = 49) or the wPTX arm (n = 51). Although the median survival time was 7.7 months in both arms, the 2-year survival rates were 2.9 % in the 5-FU arm and 9.1 % in the wPTX arm [hazard ratio 0.89 (95 % confidence interval 0.57-1.38), one-sided p = 0.298}. The median progression-free survival was longer with wPTX than with 5-FU [3.7 months vs 2.4 months; hazard ratio 0.58 (95 % confidence interval 0.38-0.88), one-sided p = 0.005]. The incidences of grade 4 neutropenia, grade 3/4 febrile neutropenia, diarrhea, and treatment-related death were 6 %, 4 %, 10 %, and 2 %, respectively, in the 5-FU arm and 2 %, 0 %, 0 %, and 0 %, respectively, in the wPTX arm.. As second-line chemotherapy, wPTX appears feasible and promising. This regimen can be included in a test arm in future phase III trials for treatment of advanced gastric cancer with severe peritoneal metastasis.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Capecitabine; Drug Combinations; Female; Fluorouracil; Follow-Up Studies; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Prognosis; Stomach Neoplasms; Survival Rate; Tegafur

First-line treatment of isolated resectable colorectal peritoneal metastases remains unclear. This study (the Swedish peritoneal study) compares cytoreductive surgery and intraperitoneal chemotherapy (surgery arm) with systemic chemotherapy (chemotherapy arm).. Patients deemed resectable preoperatively were randomised to surgery and intraperitoneal 5-fluorouracil 550 mg/m(2)/d for 6 d with repeated courses every month or to systemic oxaliplatin and 5-fluorouracil regimen every second week. Both treatments continued for 6 months. Primary end-point was overall survival (OS) and secondary end-points were progression-free survival (PFS), and morbidity.. The study terminated prematurely when 48 eligible patients (24/arm) were included due to recruitment difficulties. Two-year OS was 54% in the surgery arm and 38% in the chemotherapy arm (p = 0.04). After 5 years, 8 versus 1 patient were alive, respectively (p = 0.02). Median OS was 25 months versus 18 months, respectively, hazard ratio 0.51 (95% confidence interval: 0.27-0.96, p = 0.04). PFS in the surgery arm was 12 months versus 11 months in the chemotherapy arm (p = 0.16) with 17% versus 0% 5-year PFS. Grade III-IV morbidity was seen in 42% and 50% of the patients, respectively. No mortalities.. Cytoreductive surgery with intraperitoneal chemotherapy may be superior to systemic oxaliplatin-based treatment of colorectal cancer with resectable isolated peritoneal metastases.(ClinicalTrials.gov nr:NCT01524094).

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Cancer, Regional Perfusion; Colorectal Neoplasms; Combined Modality Therapy; Cytoreduction Surgical Procedures; Early Termination of Clinical Trials; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms

Modifications of FOLFIRINOX are widely used despite the absence of prospective data validating efficacy in metastatic disease (metastatic pancreatic cancer (MPC)) or locally advanced pancreatic cancer (LAPC). We conducted a multicentre phase II study of modified FOLFIRINOX in advanced pancreatic cancer to assess the impact of dose attenuation in MPC and efficacy in LAPC.. Patients with untreated MPC or LAPC received modified FOLFIRINOX (irinotecan and bolus 5-fluorouracil reduced by 25%). Adverse events (AEs) were compared with full-dose FOLFIRINOX. Response rate (RR), median progression-free survival (PFS) and median overall survival (OS) were determined.. In total, 31 and 44 patients with LAPC and MPC were enrolled, respectively. In MPC, efficacy of modified FOLFIRINOX was comparable with FOLFIRINOX with RR 35.1%, OS 10.2 months (95% CI 7.65-14.32) and PFS 6.1 months (95% CI 5.19-8.31). In LAPC, efficacy was notable with RR 17.2%, resection rate 41.9%, PFS 17.8 months (95% CI 11.0-23.9) and OS 26.6 months (95% CI 16.7, NA). Neutropenia (P<0.0001), vomiting (P<0.001) and fatigue (P=0.01) were significantly decreased. [(18)F]-Fluorodeoxyglucose positron emission tomography imaging response did not correlate with PFS or OS.. In this first prospective study of modified FOLFIRINOX in MPC and LAPC, we observed decreased AEs compared with historical control patients. In MPC, the efficacy appears comparable with FOLFIRINOX. In LAPC, PFS and OS were prolonged and support the continued use of FOLFIRINOX in this setting.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Female; Fluorouracil; Follow-Up Studies; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Pancreatic Neoplasms; Peritoneal Neoplasms; Prognosis; Prospective Studies; Survival Rate

A prospective randomized trial was conducted to compare the impact of systemic chemotherapy versus multi-modality therapy (complete cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC), and systemic chemotherapy) on overall survival (OS) in patients with gastric carcinomatosis.. Patients with measurable metastatic gastric adenocarcinoma involving the peritoneum, and resectable to "no evidence of disease" were randomized to gastrectomy, metastasectomy, HIPEC, and systemic FOLFOXIRI (GYMS arm) or FOLFOXIRI alone (SA arm).. Seventeen patients were enrolled (16 evaluable); 7 of 9 patients in the multi-modality GYMS arm achieved complete cytoreduction (CCR0). Median OS was 11.3 months in the GYMS arm and 4.3 months in the SA arm. Four patients in the GYMS arm survived >12 months, 2 patients close to 2 years at last follow-up, and 1 patient more than 4 years, with 2 of these patients still alive. No patient in the SA arm lived beyond 11 months. All patients surviving beyond 12 months in the surgery arm achieved complete cytoreduction and had an initial Peritoneal Cancer Index (PCI) of ≤ 15.. Maximal cytoreductive surgery combined with regional (HIPEC) and systemic chemotherapy in selected patients with gastric carcinomatosis and limited disease burden can achieve prolonged survival.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Cancer, Regional Perfusion; Female; Fluorouracil; Gastrectomy; Humans; Hyperthermia, Induced; Kaplan-Meier Estimate; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Peritoneal Neoplasms; Peritoneum; Prospective Studies; Stomach Neoplasms

Continuous treatment with FOLFOX therapy is associated with peripheral nerve toxicity, and to improve this inconvenient side effect various methods of administration are being investigated. A regimen of intermittent oxaliplatin administration by continuous infusion therapy, i.e., modified FOLFOX7 (mFOLFOX7) + bevacizumab, was designed with the goal of alleviating severe peripheral nerve disorders and hematological toxicity. A phase II clinical study was conducted to evaluate the efficacy and safety of this regimen.. Previously untreated patients were assigned to mFOLFOX7 (oxaliplatin 85 mg/m(2), levofolinate [l-LV] 200 mg/m(2), 5-fluorouracil [5-FU] 2400 mg/m(2)) + bevacizumab (5 mg/kg) administered every 2 weeks for 8 cycles, maintenance without oxaliplatin for 8 cycles, and reintroduction of mFOLFOX7 + bevacizumab for 8 cycles or until disease progression. Progression free survival (PFS) following the first dose (PFS 1) and following reintroduction of oxaliplatin (PFS 2) were used as indices for assessing the efficacy of intermittent administration.. Fifty-two patients were enrolled, with median age of 64 years (range, 36-74). Median PFS 1 was 11.8 months (95 % confidence interval [CI], 9.5 to 13.7), median time to treatment failure was 10.3 months (95 % CI, 5.6 to 12.1), percentage of patients with neutropenia of grade 3 or higher was 7.8 %, and percentage with peripheral nerve disorders was 3.9 %. Response rate was 50 %, and 84.4 % of patients who started modified simplified LV5FU2 + bevacizumab were reintroduced to oxaliplatin.. By excluding 5-FU bolus administration and administering bevacizumab continuously the mFOLFOX7 + bevacizumab regimen with preplanned withdrawal of oxaliplatin showed high tolerability and prevented severe peripheral neuropathy and neutropenia without reducing efficacy.

Topics: Adult; Aged; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colorectal Neoplasms; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Organoplatinum Compounds; Peritoneal Neoplasms; Treatment Outcome

We conducted a retrospective cohort study to compare 2 different chemotherapy regimens for advanced biliary tract cancer (BTC).. Records of patients consecutively treated in our institution for advanced BTC from 2001 to 2006 were retrieved. Chemotherapy treatment with FOLFOX-4 regimen was routinely offered as first option; gemcitabine (GEM) as single agent was proposed as an alternative option to patients who refused central venous catheter implantation. Toxicity, overall response rate, progression-free survival (PFS), and overall survival (OS) obtained with the 2 treatments were evaluated.. Twenty-two patients were treated with FOLFOX-4, whereas 18 patients received GEM. In the FOLFOX-4 group, the overall response rate was 13.6% (95% confidence interval [CI], 4.7-33.3), with 1 complete response and 2 partial responses, and 54.5% (95% CI, 34.7-73.1) of disease control rate (complete response+partial response+stable disease). Median OS was 14.1 months (95% CI, 9.1-18.8) and median PFS 5.44 months (95% CI, 3.2-6.3). In the GEM group, we observed no objective response, whereas 27.7% (95% CI, 12.5-50.9) obtained disease control. Median OS was 8.3 months (95% CI, 4.7-12.9) and median PFS 3.9 months (95% CI, 2.2-5.4). Toxicity, mainly hematological, was acceptable for both treatments. On a multivariable Cox model including a propensity score, only the performance status and chemotherapy regimen were confirmed as strong predictors of OS, with an hazard ratio of 0.49 (95% CI, 0.24-0.99) in favor of FOLFOX-4.. The combination chemotherapy with oxaliplatin and 5-fluorouracil is well tolerated and seems to provide prolonged survival than GEM alone in advanced BTC treatment, but further randomized trials are warranted.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biliary Tract Neoplasms; Bone Neoplasms; Deoxycytidine; Female; Fluorouracil; Follow-Up Studies; Gemcitabine; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms; Prognosis; Retrospective Studies; Survival Rate; Young Adult

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

Symptoms and complications of metastatic colorectal cancer (mCRC) differ by metastatic sites. There is a paucity of prospective survival data for patients with peritoneal carcinomatosis colorectal cancer (pcCRC). We characterized outcomes of patients with pcCRC enrolled onto two prospective randomized trials of chemotherapy and contrasted that with other manifestations of mCRC (non-pcCRC).. A total of 2,095 patients enrolled onto two prospective randomized trials were evaluated for overall survival (OS) and progression-free survival (PFS). A Cox proportional hazard model was used to assess the adjusted associations.. The characteristics of the pcCRC group (n = 364) were similar to those of the non-pcCRC patients in median age (63 v 61 years, P = .23), sex (57% males v 61%, P = .23), and performance status (Eastern Cooperative Oncology Group performance status 0 or 1 94% v 96%, P = .06), but differed in frequency of liver (63% v 82%, P < .001) and lung metastases (27% v 34%, P = .01). Median OS (12.7 v 17.6 months, hazard ratio [HR] = 1.3; 95% CI, 1.2 to 1.5; P < .001) and PFS (5.8 v 7.2 months, HR = 1.2; 95% CI, 1.1 to 1.3; P = .001) were shorter for pcCRC versus non-pcCRC. The unfavorable prognostic influence of pcCRC remained after adjusting for age, PS, liver metastases, and other factors (OS: HR = 1.3, P < .001; PFS: HR = 1.1, P = .02). Infusional fluorouracil, leucovorin, and oxaliplatin was superior to irinotecan, leucovorin, and fluorouracil as a first-line treatment among pcCRC (HR for OS = 0.62, P = .005) and non-pcCRC patients (HR = 0.66, P < .001).. pcCRC is associated with a significantly shorter OS and PFS as compared with other manifestations of mCRC. Future trials for mCRC should consider stratifying on the basis of pcCRC status.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Peritoneal Neoplasms; Prospective Studies

Up to 25% of patients with metastatic colorectal cancer (CRC) present with peritoneal carcinomatosis (PC) as the only site of metastases. Complete cytoreductive surgery (CCRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) aims for locoregional disease control and long-term survival. Oxaliplatin is effective for treating advanced CRC. This study assesses the safety and efficacy of CCRS with HIPEC with oxaliplatin for patients with PC of CRC.. A Belgian prospective multicenter registry was performed to monitor perioperative morbidity and assess mortality, disease-free survival (DFS), and overall survival (OS).. Forty-eight consecutive patients underwent CCRS (R0/1) with HIPEC (male/female ratio 17/31, median age 60 years, range 24-76 years). Median PC index was 11 (range 1-22). Median operation time was 460 (range 125-840) min, with a median blood loss of 475 (range 2-6,000) ml. Thirty-day mortality was 0%. Complication rate (any grade) was 52.1%. Anastomotic leakage occurred in 10.4% of patients, bleeding in 6.3%, and bowel perforation in 2.1%. Median hospital stay was 20 (range 5-65) days. At median follow-up of 22.7 (range 3.2-55.7) months, OS was 97.9% [95% confidence interval (CI) 86.1-99.7] at 1 year and 88.7% (95% CI 73.6-95.4) at 2 years. DFS at 1 year was 65.8% (95% CI 52.3-76.2) and 45.5% (95% CI 34.3-55.9) at 2 years. Median time until recurrence was 19.8 months (95% CI 12-upper limit not defined). Only after dichotomizing PC index was a significant difference in OS found between low and high PC index.. CCRS followed by HIPEC with oxaliplatin for PC from CRC can be implemented with acceptable morbidity. Long-term DFS and OS can be achieved in selected patients.

Topics: Adenocarcinoma, Mucinous; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Chemotherapy, Cancer, Regional Perfusion; Colorectal Neoplasms; Combined Modality Therapy; Female; Fluorouracil; Follow-Up Studies; Humans; Hyperthermia, Induced; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms; Prognosis; Prospective Studies; Risk Factors; Survival Rate

Oral fluoropyrimidine plus cisplatin is a standard treatment for advanced gastric cancer, but patients with severe peritoneal metastasis often cannot tolerate this regimen. The aim of this study was to assess the feasibility of fluorouracil, l-leucovorin and paclitaxel therapy in such patients.. In the first phase of the study, we investigated the maximum tolerated dose and recommended dose in Cycle 1 of fluorouracil, l-leucovorin and paclitaxel, at two dose levels [Level 1 (n = 6): 5-fluorouracil/l-leucovorin/paclitaxel = 500/250/60 mg/m(2); Level 2 (n = 6): 600/250/80 mg/m(2) on Days 1, 8 and 15, every 28 days]. Nineteen additional patients at the recommended dose level were enrolled in the second phase to investigate the feasibility of fluorouracil, l-leucovorin and paclitaxel therapy. The primary endpoint in the second phase was the completion rate of two cycles.. Dose-limiting toxicities were observed in a patient at Level 1 with Grade 4 gastrointestinal perforation (the site of primary tumor), and in two patients at Level 2 with Grade 3 febrile neutropenia and Grade 3 infection, respectively. In Cycle 2, treatment-related death occurred at Level 2 in one patient who had Grade 4 febrile neutropenia with pneumonia. The maximum tolerated dose was set at Level 2, and the recommended dose was determined as Level 1. In the second phase, the completion rate of two cycles was 92% and the ascites response was 44%. Median progression-free survival was 4.2 months and overall survival was 8.0 months. Grade 3/4 neutropenia was observed in 12% of patients.. Fluorouracil, l-leucovorin and paclitaxel at Level 1 is feasible as first-line treatment for peritoneal disseminated gastric cancer patients with massive ascites or inadequate oral intake.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Ascites; Disease-Free Survival; Drug Administration Schedule; Eating; Feasibility Studies; Female; Fluorouracil; Humans; Intestinal Perforation; Kaplan-Meier Estimate; Leucovorin; Male; Maximum Tolerated Dose; Middle Aged; Paclitaxel; Peritoneal Neoplasms; Stomach Neoplasms

This study was conducted to evaluate the efficacy and safety of combination chemotherapy with biweekly paclitaxel plus infusional 5-fluorouracil (5-FU) and leucovorin as first-line treatment for patients with advanced gastric cancer.. Eligible patients with histologically confirmed advanced or metastatic gastric cancer were enrolled. The chemotherapeutic regimen consisted of paclitaxel (100 mg/m(2) on day 1) as a 3-hour intravenous infusion, followed sequentially by leucovorin (400 mg/m(2) on day 1) as a 2-hour intravenous infusion, bolus 5-FU (400 mg/m(2) on day 1), and then continuous infusion 5-FU (3000 mg/m(2) on day 1) over 46 hours. Cycles were repeated every 2 weeks.. Sixty patients were enrolled (median age, 52.5 years old). Of these, 65% patients had Eastern Cooperative Oncology Group performance status of grade 2. A median of 8 cycles was administered (range, 4-12). Fifty-five patients were evaluable for response. Two patients achieved a complete response and 28 patients achieved a partial response, producing an overall response rate of 50% by intent-to-treat analysis. The median duration of response was 6.4 months (95% CI, 5.14-7.60 months). Median progression-free survival and median overall survival were 7.7 months (95% CI, 6.5-8.9 months) and 14.3 months (95% CI, 9.4-19.1 months), respectively. Hematologic toxicity was mild; grade 3 neutropenia was noted in only 6.7% of patients. Alopecia was the most common nonhematologic toxicity in 51 patients (71.4%). Grade 3 alopecia occurred in 11 patients (18.3%).. Combination chemotherapy of biweekly paclitaxel followed sequentially by infusion leucovorin, bolus 5-FU, and continuous infusion 5-FU over 46 hours is effective and well tolerated in patients with advanced gastric cancer, especially in patients with poor performance status who cannot tolerate aggressive chemotherapy regimens.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Signet Ring Cell; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Paclitaxel; Peritoneal Neoplasms; Skin Neoplasms; Stomach Neoplasms; Survival Rate; Time Factors; Treatment Outcome

To determine the activity and toxicities of a low-dose leucovorin plus 5-fluorouracil (5-FU) regimen, combined with irinotecan and administered every 2 weeks (modified FOLFIRI), as a first-line therapy for patients with advanced gastric cancer.. Patients were treated with cycles of 150 mg/m irinotecan on day 1 plus 50 mg of LV, followed by a 400 mg/m 5-FU bolus and a 22-hour continuous infusion of 600 mg/m 5-FU on days 1 and 2.. The median patient age was 55 years (range, 29-75 years), and 77% (34/44) of the patients had a performance status (Eastern Cooperative Oncology Group) of 0 or 1. Of the 44 patients evaluated for their tumor response, 3 patients (6.8%) and 14 patients (31.8%) achieved a complete and partial response, respectively, with an overall response rate of 38.6% (95% confidence interval, 23.7%-53.6%). 13 patients (29.6%) evidenced a stable disease, and 14 patients (31.8%) progressed during the course of the treatment. The median time to progression and overall survival time were 4.9 months (range, 0.9-22.8 months) and 10.3 months (range, 1.2-29.0 months) from the start of the chemotherapy, respectively. A total of 293 cycles were assessed for toxicity. The major hematologic toxicities included grade 1 to 2 anemia (27.6%), neutropenia (48.8%), and grade 3 to 4 neutropenia (12.6%). There were 7 cycles of neutropenic fever. Nonhematological toxicities were observed grade 3 vomiting (6.8%), grade 3 diarrhea (4.5%), and grade 3 mucositis (2.3%). We noted no treatment-related deaths.. The modified FOLFIRI regimen-lowering of irinotecan and LV doses-is a safe and feasible regimen as a first-line therapy for patients with recurrent or metastatic gastric cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Combined Modality Therapy; Drug Administration Schedule; Female; Fluorouracil; Gastrectomy; Gastrointestinal Diseases; Humans; Irinotecan; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Peritoneal Neoplasms; Salvage Therapy; Stomach Neoplasms; Treatment Outcome

The standard of care for colorectal peritoneal carcinomatosis is evolving from chemotherapy to cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with disease limited to the peritoneum. Peritoneal carcinomatosis from colorectal cancer treated with chemotherapy alone results in median survival of 5 to 13 months, whereas CRS with HIPEC for early peritoneal carcinomatosis from colorectal cancer resulted in median survival of 48-63 months and 5 year survival of 51%.Completeness of cytoreduction and limited disease are associated with longer survival, yet early peritoneal carcinomatosis is undetectable by conventional imaging. Exploratory laparotomy can successfully identify early disease, but this approach can only be justified in patients with high risk of peritoneal carcinomatosis. Historical data indicates that patients presenting with synchronous peritoneal carcinomatosis, ovarian metastases, perforated primary tumor, and emergency presentation with bleeding or obstructing lesions are at high risk of peritoneal carcinomatosis. Approximately 55% of these patient populations will develop peritoneal carcinomatosis. We hypothesize that performing a mandatory second look laparotomy with CRS and HIPEC for patients who are at high risk for developing peritoneal carcinomatosis from colorectal cancer will lead to improved survival as compared to patients who receive standard of care with routine surveillance.. This study is a prospective randomized trial designed to answer the question whether mandatory second look surgery with CRS and HIPEC will prolong overall survival compared to the standard of care in patients who are at high risk for developing peritoneal carcinomatosis from colorectal cancer (CRC). Patients with CRC at high risk for developing peritoneal carcinomatosis who underwent curative surgery and subsequently received standard of care adjuvant chemotherapy will be evaluated. The patients who remain without evidence of disease by imaging, physical examination, and tumor markers for 12 months after the primary operation will be randomized to mandatory second look surgery or standard-of-care surveillance. At laparotomy, CRS and HIPEC will be performed with intraperitoneal oxaliplatin with concurrent systemic 5-fluorouracil and leucovorin. Up to 100 patients will be enrolled to allow for 35 evaluable patients in each arm; accrual is expected to last 5 years.. ClinicalTrials.gov ID: NCT01095523.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Chemotherapy, Cancer, Regional Perfusion; Colorectal Neoplasms; Disease-Free Survival; Fluorouracil; Humans; Hyperthermia, Induced; Laparotomy; Leucovorin; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms; Prospective Studies; Risk Assessment; Risk Factors; Sample Size; Second-Look Surgery; Time Factors; Treatment Outcome

This prospective study was conducted with the Korean Cancer Study Group to evaluate the efficacy and safety of cetuximab combined with modified FOLFOX6 (mFOLFOX6) as first-line treatment in recurrent or metastatic gastric cancer and to identify potential predictive biomarkers. Patients received cetuximab 400 mg m(-2) at week 1 and 250 mg m(-2) weekly thereafter until disease progression. Oxaliplatin (100 mg m(-2)) and leucovorin (100 mg m(-2)) were administered as a 2-h infusion followed by a 46-h continuous infusion of 5-fluorouracil (2400 mg m(-2)) every 2 weeks for a maximum of 12 cycles. Biomarkers potentially associated with efficacy were analysed. Among 38 evaluable patients, confirmed response rate (RR) was 50.0% (95% CI 34.1-65.9). Median time-to-progression (TTP) was 5.5 months (95% CI 4.5-6.5) and overall survival (OS) 9.9 months. Eleven patients having tumour EGFR expression by immunohistochemistry with low serum EGF and TGF-alpha levels showed a 100% RR compared to 37.0% in the remaining 27 patients (P<0.001). Moreover, ligand level increased when disease progressed in seven out of eight patients with EGFR expression and low baseline ligand level. No patient exhibited EGFR amplification or K-ras mutations. Gastric cancer patients with EGFR expression and low ligand levels had better outcomes with cetuximab/mFOLFOX6 treatment.

Topics: Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Cetuximab; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms; Prognosis; Prospective Studies; Stomach Neoplasms; Survival Rate; Treatment Outcome

A phase II study was performed to assess the activity of oxaliplatin plus 5-fluorouracil (5-FU) modulated by leucovorin, as second-line treatment in locally advanced or metastatic pancreas adenocarcinoma pretreated with gemcitabine-containing schedule.. Patients received weekly intravenous infusions of oxaliplatin 40 mg/m, 5-FU 500 mg/m, and leucovorin 250 mg/m (3 weeks on, 1 week off).. Twenty-three patients affected with metastatic (16) or locally advanced (7) pancreas adenocarcinoma were involved in this study. A total of 148 weeks of chemotherapy was delivered (median 2 courses each patient). Among 17 assessable patients, no objective response was registered and 4 patients had stable disease, whereas 13 had tumor progression. Median duration of stable disease was 14 weeks. Median time to progression of disease (TTP) was 11.6 weeks [95% confidence interval (CI), 7.6-5.6]. Kaplan-Meier estimated median overall survival (OS) was 17.1 week (95% CI, 4.0-30.1) and 3 months survival rate was 69.6%. Seven patients experienced grade 3 to 4 toxicity. The regimen was associated with 36% clinical benefit.. The median TTP and median OS in this population with poor prognosis suggests some activity, however, only further investigations will be able to establish the clinical value of this combination.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cohort Studies; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Maximum Tolerated Dose; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Pancreatic Neoplasms; Peritoneal Neoplasms; Prognosis; Salvage Therapy; Survival Rate; Treatment Outcome

Irinotecan has, in general, been administered as a 90-min infusion. However, several studies have demonstrated that continuous infusion seems to be a promising method of delivering irinotecan. This phase I/II trial was performed to evaluate the efficacy and safety of continuous infusion of irinotecan combined with UFT plus leucovorin (LV) for metastatic colorectal cancer.. Escalating doses of irinotecan (90-110 mg/m(2)) were administered by 24-hour infusion on day 1. UFT 300 mg/m(2)/day and LV 75 mg/day were administered orally, in 3 divided daily doses, on days 3-7 and 10-14. The treatment cycles were repeated every 2 weeks.. In the phase I study, the maximum tolerated dose of irinotecan was 110 mg/m(2) and the recommended dose for the phase II study was determined to be 100 mg/m(2). Thirty-six patients, including 3 patients at the recommended dose in the phase I study, were evaluated in the phase II study. The common grade 3/4 toxicities were leucopenia, neutropenia, diarrhea and anorexia. The response rate was 63.9%, and the median progression-free and overall survival times were 8.3 and 24.6 months, respectively.. A 24-hour infusion of irinotecan combined with UFT/LV is feasible and active for metastatic colorectal cancer.

Topics: Adenocarcinoma; Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Dose-Response Relationship, Drug; Female; Humans; Infusions, Intravenous; Irinotecan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Staging; Peritoneal Neoplasms; Prognosis; Survival Rate; Tegafur; Treatment Outcome; Young Adult

The treatment of peritoneal carcinomatosis is based on cytoreduction followed by hyperthermic intraperitoneal chemotherapy and combined with adjuvant chemotherapy. In 2003, a randomized trial was finished comparing systemic chemotherapy alone with cytoreduction followed by hyperthermic intraperitoneal chemotherapy and systemic chemotherapy. This trial showed a positive result favoring the studied treatment. This trial has now been updated to a minimal follow-up of 6 years to show long-term results.. For all patients still alive, the follow-up was updated until 2007. In the original study, four patients were excluded-two because of no eligible histology/pathology and two because of major protocol violations. After randomization, four patients in the HIPEC arm and six in the control arm were not treated using the intended therapy, one patient because of withdrawal, one because of a life-threatening other malignant disease and the others because of progressive disease before initiation of the treatment. During the follow-up, one patient was crossed over from the control arm and underwent cytoreduction and HIPEC for recurrent disease, after the assigned treatment was completed. The data from these patients were censored at the moment of the cross-over. Progression-free and disease-specific survival were analyzed using the Kaplan Meyer test and compared using the log rank method. The long-term results were studied in more detail to evaluate efficacy and toxicity.. At the time of this update, the median follow-up was almost 8 years (range 72-115 months). In the standard arm, 4 patients were still alive, 2 with and 2 without disease; in the "HIPEC' arm, 5 patients were still alive, 2 with and 3 without disease. The median progression-free survival was 7.7 months in the control arm and 12.6 months in the HIPEC arm (P = 0.020). The median disease-specific survival was 12.6 months in the control arm and 22.2 months in the HIPEC arm (P = 0.028). The 5-year survival was 45% for those patients in whom a R1 resection was achieved.. With 90% of all events having taken place up to this time, this randomized trial shows that cytoreduction followed by HIPEC does significantly add survival time to patients affected by peritoneal carcinomatosis of colorectal origin. For a selected group, there is a possibility of long-term survival.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Cancer, Regional Perfusion; Colorectal Neoplasms; Combined Modality Therapy; Female; Fluorouracil; Follow-Up Studies; Humans; Hyperthermia, Induced; Injections, Intraperitoneal; Laparotomy; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Peritoneal Neoplasms; Prognosis; Survival Rate; Tomography, X-Ray Computed; X-Rays

Peritoneal carcinomatosis (PC), which has hitherto been regarded as a lethal entity, can now be cured with surgery (treating macroscopic tumor seeding) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) (treating residual microscopic disease). The purpose of this study was to analyze the morbidity and mortality of a particular approach associating optimal (R0-R1) cytoreduction, optimal HIPEC combining oxaliplatin and irinotecan, and an optimal homogeneous intraperitoneal temperature of 43 degrees C.. A total of 106 consecutive patients were included in this prospective phase 2 study. After complete resection of the PC, HIPEC was performed by the Coliseum technique with oxaliplatin (360 mg/m2) combined with irinotecan (360 mg/m2) in 2 L/m2 of 5% dextrose, over 30 minutes at a real intraperitoneal temperature of 43 degrees C. During the hour preceding HIPEC, patients received 5-fluorouracil (400 mg/m2) and leucovorin (20 mg/m2) intravenously, resulting in tritherapy.. Postoperative mortality and morbidity rates were 4% and 66%, respectively. The most frequent complications were digestive fistula (24%), lung infection (16%), and severe hematological toxicity (11%). Statistical correlation was evidenced between morbidity and the carcinomatosis score (P = .0008), the number of resected organs (P = .0001), the duration of surgery (P = .0001), and blood loss (P = .0001).. This new approach, optimized in three respects (complete cytoreduction, combination oxaliplatin with irinotecan, and high temperature) has resulted in a relatively high but acceptable incidence of adverse events considering the expected advantage for survival.

Topics: Adolescent; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Blood Loss, Surgical; Camptothecin; Carcinoma; Female; Fluorouracil; Humans; Hyperthermia, Induced; Injections, Intraperitoneal; Irinotecan; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms; Postoperative Complications; Prospective Studies; Survival Rate; Topoisomerase I Inhibitors; Vitamin B Complex

More than two-thirds of patients with gastric cancer present with metastatic disease and their curative options are limited. This phase II study assessed the efficacy and tolerability of cisplatin, epirubicin, tegafur-uracil (UFT) and leucovorin in patients with metastatic gastric cancer (MGC). Thirty-nine patients with previously untreated metastatic or unresectable gastric cancer received intravenous cisplatin 60 mg/m2 and epirubicin 50 mg/m2 on day 1 of a 28-day cycle; UFT 300 mg/m2 was administered with oral leucovorin 30 mg/day in divided doses on days 1-22, followed by a 7-day rest. Two patients achieved a complete response, 13 had a partial response (overall response rate 38%; 95% confidence interval [CI] 24-52%) and 16 patients (41%) had stable disease. Median time to progression was 6.5 months (95% CI 5.5-7.5 months); overall survival was 9.5 months (95% CI 8.5-13.5 months). Grade 3/4 neutropenia, anemia, and thrombocytopenia occurred in 20%, 8%, and 3% of patients, respectively; two patients experienced febrile neutropenia. Grade 3 diarrhea occurred in three patients. The combination of cisplatin, epirubicin, UFT, and leucovorin has significant activity and tolerable toxicities in patients with MGC and represents a convenient treatment option for these patients.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cisplatin; Dose-Response Relationship, Drug; Drug Administration Schedule; Epirubicin; Female; Follow-Up Studies; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Peritoneal Neoplasms; Stomach Neoplasms; Survival Analysis; Tegafur; Time Factors; Treatment Outcome; Uracil

Complete resection of macroscopic colorectal peritoneal carcinomatosis (PC), followed by intraoperative intraperitoneal chemohyperthermia (IPCH) to treat residual microscopic disease achieves cure in some patients. We report long-term results concerning survival of a phase II study using oxaliplatin (LOHP).. From June 1998 to December 2003, thirty patients with macroscopic colorectal PC underwent complete resection of PC followed by IPCH with LOHP performed in an open abdominal cavity. The dose of LOHP was 460 mg/m2 in 2 L/m2 of iso-osmotic 5% dextrose, over 30 min at an intraperitoneally homogenous temperature of 43 degrees C and at a flow rate of 2 L/min in the continuous closed circuit. During the hour preceding IPCH, patients received 5-fluorouracil (400 mg/m2) and leucovorin (20 mg/m2) intravenously. All patients received neoadjuvant and adjuvant systemic chemotherapy.. Mean peritoneal tumor extension (Sugarbaker's Score) was 14.3 +/- 3.8, median operative duration, 450 min, and median blood loss, 940 mL. Eleven (37%) patients had associated extra-peritoneal lesions which were resected during the same procedure. There were no postoperative deaths and grade 2-3 morbidity (requiring specific treatment) was 40%. Median follow-up was 55 months (range: 31-84). Twenty-two patients (73%) relapsed after a median interval of 14 months, but 7 of them (32%) were amenable to curative repeat surgery. At 3 and 5 years, overall survival rates (95% confidence interval) were 53% (9-72), and 48.5% (31-66) respectively. At 3 and 5 years, disease-free survival rates were 41.5% (27-59), and 34% (19-52) respectively. Median survival was 60.1 months.. When feasible, this treatment modality yields a 5-year survival rate of 48.5%, with median survival attaining 60.1 months.

Topics: Adult; Antimetabolites, Antineoplastic; Antineoplastic Agents; Carcinoma; Chemotherapy, Adjuvant; Colorectal Neoplasms; Combined Modality Therapy; Confidence Intervals; Data Interpretation, Statistical; Disease-Free Survival; Female; Fluorouracil; Follow-Up Studies; Humans; Hyperthermia, Induced; Injections, Intraperitoneal; Injections, Intravenous; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms; Reoperation; Survival Analysis; Time Factors; Vitamin B Complex

Peritoneal carcinomatosis (PC) is a major disease, currently treated using complete cytoreductive surgery and intraperitoneal chemohyperthermia (IPCH). Morbidity is a significant limitation of this procedure, usually related to the extent of surgery, and hematological toxicity, which is considered as dependent upon the chemotherapy dosage alone. The aim of our study was to investigate whether surgery alone had an impact on the hematological toxicity associated with the standardized drug protocol that we routinely prescribed.. Data were prospectively recorded from 83 consecutive patients who underwent complete cytoreductive surgery followed by IPCH with intraperitoneal oxaliplatin (360 mg/m(2)) and irinotecan (360 mg/m(2)), in 2 L/m(2) of dextrose over 30 min at 42-45 degrees C, using the Coliseum technique. Sixty minutes prior to IPCH, patients also received an intravenous perfusion of leucovorin (20 mg/m(2)) and 5-fluorouravyl (400 mg/m(2)). The doses and volume of IPCH were determined on the basis of the body surface area, so that all patients received the same concentration of drugs. Severe aplasia were defined as a leucocyte count of <500/ml, platelets <50,000/ml, and reticulocytes <6.5 g Hb/L.. Postoperatively, severe aplasia was seen in 40 of the 83 patients (48%). There was no difference in the characteristics of patients with and without aplasia, other than the extent of surgery. The incidence of severe aplasia was only related to the duration of surgery (537 min in the aplastic group versus 444 min in the non aplastic group) (P = 0.002), and to the extent of the peritoneal disease (peritoneal index of 19.5 in the aplastic group, vs. 15.3 in the nonaplastic group) (P = 0.02).. We report for the first time that the duration of surgery may increase the incidence of hematological toxicity following intraperitoneal chemotherapy. We also hypothesized that intra- and postoperative transient biochemical disorders, such as hypoalbuminemia, hemodilution, liver, and renal insufficiency and stress can be involved in this process. These hypotheses may allow improved postoperative care.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Combined Modality Therapy; Dose-Response Relationship, Drug; Female; Fluorouracil; Glucose; Hemodilution; Humans; Hyperthermia, Induced; Hypoalbuminemia; Infusions, Parenteral; Irinotecan; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms; Postoperative Period; Prospective Studies; Red-Cell Aplasia, Pure; Treatment Outcome

An open-label randomised comparison of efficacy and tolerability of irinotecan plus high-dose 5-fluorouracil (5-FU) and leucovorin (LV) (ILF) with etoposide plus 5-FU/LV (ELF) in patients with untreated metastatic or locally advanced gastric cancer. One cycle of ILF comprised six once-weekly infusions of irinotecan 80 mg m(-2), LV 500 mg m(-2), 24-h 5-FU 2000 mg m(-2), and ELF comprised three once-daily doses of etoposide 120 mg m(-2), LV 300 mg m(-2), 5-FU 500 mg m(-2). In all, 56 patients received ILF and 58 ELF. Median age was 62 years, Karnofsky performance 90%, and disease status was comparable for both arms. The objective clinical response rates after 14 weeks treatment (primary end point) were 30% for ILF and 17% for ELF (risk ratio (RR) 0.57, 95% confidence interval (CI) 0.29-1.13, P = 0.0766). Overall response rates over the entire treatment period for ILF and ELF were 43 and 24%, respectively (RR 0.56, 95% CI 0.33-0.97; P = 0.0467). For ILF and ELF, respectively, median progression-free survival was 4.5 vs 2.3 months, time to treatment failure was 3.6 vs 2.2 months (P = 0.4542), and overall survival was 10.8 vs 8.3 months (P = 0.2818). Both regimens were well tolerated, the main grade 3/4 toxicities being diarrhoea (18%, ILF) and neutropenia (57%, ELF). The data from this randomised phase II study indicate that ILF provides a better response rate than ELF, and that ILF should be investigated further for the treatment of metastatic gastric cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Esophagogastric Junction; Etoposide; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Levoleucovorin; Male; Middle Aged; Neoplasm Staging; Peritoneal Neoplasms; Stomach Neoplasms; Survival Analysis; Treatment Outcome

Patients with peritoneal or local metastases from colorectal cancer have a poor prognosis. However, aggressive treatments by debulking surgery and infusional intraperitoneal (i.p.) chemotherapy have been tried and appear to benefit selected patients. We assayed the effects of debulking surgery and i.p. chemotherapy with respect to survival and compared the results with matched control patients treated by intravenous (i.v.) chemotherapy. In all, 18 patients with peritoneal and/or local metastases from colorectal adenocarcinoma underwent debulking surgery followed by 5-fluorouracil (5-FU) 550 mg m(-2) day(-1) i.p. and leucovorin (LV) 60 mg m(-2) day(-1) i.v. The chemotherapy was started the day after surgery and was given daily for 6 days and repeated monthly for totally eight courses. The control patients, matched for age, gender, performance status and metastatic site, were randomly selected from controlled clinical chemotherapy trials and treated with i.v. 5-FU+LV or i.v. methotrexate+5-FU+LV. There was no treatment-related mortality. The median survival among i.p. patients was 32 months compared to 14 months in the control group. In all, 11 patients who underwent macroscopically radical surgery had a longer survival than those who were not radically operated (P=0.02). These results indicate that patients with peritoneal metastases and/or locally advanced cancers but without distant metastases may benefit from cytoreductive surgery combined with i.p. chemotherapy.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Combined Modality Therapy; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Methotrexate; Middle Aged; Peritoneal Neoplasms; Prognosis; Survival Analysis; Treatment Outcome

Cytoreduction with hyperthermic intra-peritoneal chemotherapy (HIPEC) is a treatment with a high morbidity. Optimal patients selection can possible reduce toxicity and complications.. Complications and toxicity of 102 patients were studied. Toxicity was graded according National Cancer Institute Common Toxicity Criteria (NCI CTC) classification. A complication was defined as any post-operative event that needed re-intervention. Potential patients, tumor, and treatment factors were studied on their relation to complications.. Grade 3, 4, or 5 toxicity was observed in 66 patients (65%). Eight patients died of treatment-related causes. Surgical complications occurred in 36 patients (35%). Fistulae were frequently encountered (18 patients). The risk of a complicated recovery was higher in carcinomatosis with recurrent colorectal cancer (P = 0.009) and in the case of more than five regions affected (P = 0.044), who had a Simplified Peritoneal Cancer (SPC) score of 13 (P = 0.012) and with an incomplete initial cytoreduction (P = 0.035). Patients with blood loss exceeding 6 L (P = 0.028) and those with three or more anastomoses also had an increased post-operative complication rate (P = 0.018).. Toxicity of cytoreduction followed by HIPEC was 65% (Grade 3-5 NCI CTC), with a surgical complication rate of 35%. Patients with six or seven regions involved and those in whom complete cytoreduction cannot be reached are probably better off without this treatment.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Appendiceal Neoplasms; Carcinoma; Cecum; Chemotherapy, Adjuvant; Colorectal Neoplasms; Female; Fluorouracil; Humans; Hyperthermia, Induced; Hysterectomy; Infusions, Parenteral; Intestine, Small; Leucovorin; Male; Middle Aged; Peritoneal Neoplasms; Postoperative Complications; Postoperative Nausea and Vomiting; Rectum; Survival Analysis

The complete resection of macroscopic colorectal peritoneal carcinomatosis (PC), followed by intraoperative intraperitoneal chemohyperthermia (IPCH) to treat residual microscopic disease, leads to cure in some patients. We report preliminary results on survival in a phase II study using oxaliplatin (LOHP).. Twenty-four patients with macroscopic colorectal PC underwent complete resection of the PC followed by IPCH with LOHP performed in an open abdominal cavity. The dose of LOHP was 460 mg/m(2) in 2 l/m(2), during 30 min at 43 degrees C, at a flow rate of 2 l/min. During the hour preceding IPCH, they received an intravenous administration of 5-fluorouracil (400 mg/m(2)) and leucovorin (20 mg/m(2)).. Mean peritoneal tumoral extension (Sugarbaker's Index) was 16.9 +/- 9.5, median operative duration was 490 min and median blood loss was 965 ml. There were two postoperative deaths (8%) by intracerebral hemorrhage, and morbidity rate was 41.6%. Minimal follow-up was 18 months and median follow-up was 27.4 months (range 18.3-49.6). At 1, 2 and 3 years, overall survival rates were 83%, 74% and 65%, and disease-free survival rates were 70%, 50% and 50%, respectively. Only 32% of the 22 postoperative living patients presented a peritoneal recurrence. A peritoneal index >24 influenced survival, with a 17% recurrence rate at 2 years versus 63% when it was <24 (P = 0.005).. This new modality of treatment, when feasible, gives encouraging preliminary results, with a promising 3-year survival rate of 65%.

Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Combined Modality Therapy; Female; Fluorouracil; Humans; Hyperthermia, Induced; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm, Residual; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms; Prospective Studies; Survival Analysis; Treatment Outcome

Colorectal peritoneal carcinomatosis (PC) is a frequent and very lethal event. However, cure may be possible with maximal cytoreductive surgery associated with early postoperative intraperitoneal chemotherapy (EPIC).. Between 1996 and 2000, we conducted a two-center prospective randomized trial comparing EPIC plus systemic chemotherapy with systemic chemotherapy alone, both after complete cytoreductive surgery of colorectal PC. Only 35 patients could be included among the 90 who were theoretically required, mainly because of patient dissatisfaction with the inclusion criteria. For this reason, the trial was stopped prematurely.. Analysis of these 35 patients showed that complete resection of PC resulted in a 2-year survival rate of 60%-far above the classic 10% survival rate among patients with colorectal PC treated with systemic chemotherapy and symptomatic surgery. In this small series, EPIC did not demonstrate any advantage for survival.. This supports the use of complete cytoreductive surgery in selected patients and calls for a prospective randomized trial comparing adjuvant systemic chemotherapy with intraperitoneal chemohyperthermia after complete resection.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Chemotherapy, Adjuvant; Colorectal Neoplasms; Eligibility Determination; Female; Fluorouracil; Humans; Infusions, Parenteral; Leucovorin; Male; Middle Aged; Patient Satisfaction; Peritoneal Neoplasms; Prospective Studies; Survival Analysis

Peritoneal carcinomatosis in the absence of distant metastasis occurs in approximately 8 per cent of patients with colorectal cancer. Cytoreduction followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is a new treatment option. Patient selection is crucial to outcome.. Cytoreduction followed by HIPEC was performed in 102 patients with peritoneal carcinomatosis. The following factors were studied for association with survival: perforation and obstruction of the primary lesion, location of the primary lesion, obstruction associated with carcinomatosis, presentation, tumour differentiation and histological type. Extent of disease and completeness of cytoreduction were also studied. Hazard ratios (HRs) were used to study these factors.. Location of the primary tumour in rectum (HR 3.14 (95 per cent confidence interval (c.i.) 1.11 to 8.91); P = 0.069), poor differentiation (HR 1.73 (95 per cent c.i. 1.04 to 2.88); P = 0.031) and signet cell histological type (HR 2.24 (95 per cent c.i. 1.21 to 4.16); P = 0.008) were associated with shorter survival. Important factors predicting survival were the number of affected regions (HR 1.38 (95 per cent c.i. 1.20 to 1.59); P < 0.001), the simplified peritoneal cancer score (HR 1.19 (95 per cent c.i. 1.12 to 1.26); P < 0.001) and completeness of cytoreduction (HR 8.54 (95 per cent c.i. 4.01 to 18.18); P < 0.001). No other factor correlated with survival.. The survival of patients with peritoneal carcinomatosis of colorectal origin is dominated by the extent of disease and the amount of residual tumour after cytoreduction.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Chemotherapy, Adjuvant; Colorectal Neoplasms; Combined Modality Therapy; Female; Fluorouracil; Humans; Hyperthermia, Induced; Laparotomy; Leucovorin; Male; Middle Aged; Neoplasm, Residual; Peritoneal Neoplasms; Survival Analysis

The efficacy of systemic chemotherapy against peritoneal dissemination from advanced gastric cancer (AGC) remains unclear, because the peritoneal dissemination was not defined as a measurable lesion in conventional phase II studies. In this study, we evaluated the efficacy and toxicity of sequential MTX and 5FU therapy (MF) in chemotherapy-naive patients with AGC accompanied by malignant ascites in a phase II setting.. The treatment schedule comprised weekly administration of MTX (100 mg/m2, i.v. bolus) followed by 5FU (600 mg/m2, i.v. bolus) with a 3 h interval. Leucovorin rescue (10 mg/m2 every 6 h, for a total of six times) was commenced 24 h after MTX administration.. Thirty-seven chemotherapy-naive patients with AGC presenting with malignant ascites were enrolled in this trial. The median age was 60 years (range, 25-74 years) and most patients (86%) had a performance status of 0-1. In total, 355 administrations of the sequential MTX/5FU therapy were performed. Major toxicity consisted of myelosuppression and gastrointestinal toxicity. Grade 4 neutropenia occurred in 10.8% of the patients. The overall objective response rate was 5.7% (two partial responses in 35 patients; 95% confidence interval: 0.7-19.2%). However, the response rate of ascites was 35.1% (complete disappearance in three patients and apparent decrease in 10 patients; 95% confidence interval: 20.2-52.5%).. Sequential MTX/5FU therapy is effective against AGC with malignant ascites with acceptable toxicity and warrants further investigations in a phase III setting.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Ascites; Drug Administration Schedule; Female; Fluorouracil; Humans; Japan; Leucovorin; Male; Methotrexate; Middle Aged; Peritoneal Neoplasms; Stomach Neoplasms; Survival Rate

We studied the pharmacokinetics of heated intraoperative intraperitoneal (i.p.) oxaliplatin (LOHP) solution and its safety profile in increasingly hypotonic solutions. This is the first clinical study of i.p. chemohyperthermia with hypotonic solutions.. Patients with peritoneal carcinomatosis (PC) underwent complete cytoreductive surgery followed by intraoperative i.p. chemohyperthermia (IPCH) with successive dextrose solutions of 300, 200, 150 and 100 mosm/l. LOHP (460 mg/m(2)) was administered in 2 liters of solution/m(2) at an i.p. temperature of 42-44 degrees C for 30 min. IPCH was performed using an open procedure (skin pulled upwards) with a continuous closed circuit. Patients received intravenous leucovorin (20 mg/m(2)) and 5-fluorouracil (400 mg/m(2)) just before IPCH to maximize the effect of LOHP. i.p. plasma and tissue samples were analyzed by means of atomic absorption spectrophotometry. Sixteen consecutive patients with PC of either gastrointestinal or peritoneal origin were treated. The safety of the procedure was studied.. Pharmacokinetics: The mean duration of the entire procedure was 7.7 +/- 2.6 h. Half the LOHP dose was absorbed within 30 min at all dose levels. Absorption was not higher with hypotonic solutions than with isotonic solutions. The area under the curve of LOHP in plasma did not increase with decreasing osmolarity of the i.p. solutions. Intratumoral LOHP penetration was high; it was similar to that at the peritoneal surface, and about 18 times higher than that in nonbathed tissues. LOHP penetration was not significantly increased by using hypotonic solutions.. There was a very high incidence of unexplained postoperative peritoneal bleeding (50%) and unusually severe thrombocytopenia in the 150 and 100 mosm/l groups.. Contrary to experimental studies, this clinical study showed no increase in tumoral or systemic penetration of LOHP with i.p. hypotonic solutions (200, 150 or 100 mosm/l) during IPCH. A high incidence of i.p. hemorrhage and thrombocytopenia was observed.

Topics: Antineoplastic Agents; Carcinoma; Female; Fluorouracil; Hot Temperature; Humans; Hyperthermia, Induced; Hypotonic Solutions; Intraoperative Care; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms; Spectrophotometry, Atomic

The present study aimed at evaluating the efficacy of Raltitrexed, a specific thymidilate synthase inhibitor, in patients with advanced colorectal cancer (ACC) in relapse (>8 weeks) after a prior response or disease stabilization to first-line chemotherapy combination with lrinotecan+5-Fluorouracil (5-FU)+Leucovorin (LV).. Twenty-five patients with metastatic ACC entered; 17 males/8 females, median age 61 (range: 47-70), median Karnovsky PS: 80 (70-90), and sites of metastases; liver: 21, lung: 4, lymph nodes: 7, peritoneal: 5 and a life expectancy of at least 3 months, were entered in the present pilot study. All patients had progressed after prior chemotherapy with lrinotecan+5-FU+LV. Raltitrexed was administered at a dose of 3 mg/m2 i.v. every 21 days.. Three patients (12%) achieved a partial response (PR), 8 (32%) had stable disease (SD), and the remaining 14 (56%) developed progressive disease (PD). Median time-to-progression (TTP) was 5.5 months (range, 2-8.5), and median overall survival (OS) 8 months (range, 4.0-12.5). Toxicity was generally mild; it consisted mainly of myelosuppression; neutropenia grade 1-2: 52%-grade 3: 28%, and anemia grade 1-2 only: 36%. Mild mucositis grade 1-2 occurred in 13.5% of patients and was the principal non-hematologic toxicity.. Response to treatment with Raltitrexed is limited in patients with ACC failing after an initial response or non-progression to the weekly lrinotecan+5-FU+LV combination. However, it appears that a limited number of patients with PR/SD may derive clinical benefit, but final proof would require a randomized study.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Peritoneal Neoplasms; Quinazolines; Salvage Therapy; Secondary Prevention; Thiophenes; Treatment Outcome

Peritoneal seeding from colorectal cancer has a very poor prognosis and is relatively resistant to systemic chemotherapy. We performed a phase I/II trial to investigate the feasibility and effectiveness of extensive cytoreductive surgery in combination with intra-operative hyperthermic intraperitoneal chemotherapy (HIPEC) in these patients. 29 patients with peritoneal carcinomatosis of colorectal origin without evidence of distant metastases underwent cytoreductive surgery and intra-operative HIPEC with mitomycin-C (MMC), followed by systemic chemotherapy with 5-fluorouracil (5-FU)/leucovorin. Surgical complications occurred in 11 patients (38%). One patient died directly related to the treatment, resulting in a mortality rate of 3%. MMC toxicity existed mainly of leucocytopenia (in 15 patients; 52%). After a median follow-up of 38 months (range 26-52 months) we found a 2- and 3-year survival rate (Kaplan-Meier) of 45 and 23%, respectively. Extensive cytoreductive surgery and HIPEC is feasible in patients with peritoneal seeding of colorectal cancer. First results suggest that a higher median survival could be achieved compared with conventional palliative surgery and systemic chemotherapy, therefore a randomised phase III study is now being conducted.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Cancer, Regional Perfusion; Colorectal Neoplasms; Combined Modality Therapy; Female; Fluorouracil; Follow-Up Studies; Humans; Hyperthermia, Induced; Intraoperative Care; Leucovorin; Male; Middle Aged; Mitomycin; Peritoneal Neoplasms; Postoperative Complications; Survival Analysis; Treatment Outcome

This phase II study examined a regimen (FOLFOX7) of leucovorin (LV), high-dose intensity oxaliplatin, and 5-fluorouracil (5-FU), as second-line therapy for metastatic colorectal cancer. 48 patients were enrolled - 36 refractory and 12 resistant to prior therapy with LV-5-FU. Oxaliplatin (130 mg/m2) was infused with LV (400 mg/m2) over 2 h on day 1, followed by bolus 400 mg/m2 and a 46-h infusion (2400 g/m2) of 5-FU, every 2 weeks. Patients who responded or were stable received eight cycles. Patients were evaluated every 2 months. 20 patients (42%) had partial responses (95% confidence interval (CI): 28-56%), 19 (40%) had stable disease and 9 (19%) progressed. Median progression-free survival (PFS) was 6 months and median survival 16.1 months. Toxic effects of National Cancer Institute-Common Toxicity Criteria (NCI-CTC) grade 3/4 were: peripheral neuropathy 15%, nausea 8%, diarrhoea 11%, neutropenia 9%, thrombocytopenia 11%. Overall, 38% of patients experienced grade 3/4 toxicities, and 64% received 90% or more of the scheduled oxaliplatin dose intensity during the first four cycles. FOLFOX7 was highly active, with good tolerability, in pretreated patients resistant to LV-5-FU [corrected].

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Drug Resistance, Neoplasm; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Organoplatinum Compounds; Oxaliplatin; Palliative Care; Peritoneal Neoplasms; Survival Analysis; Treatment Outcome

To evaluate the toxicity and efficacy of combination chemotherapy with paclitaxel, cisplatin and 24 h continuous infusion of 5-FU/folinic acid in patients (pts) with unresectable, locally advanced or metastatic gastric adenocarcinoma. Forty-five chemotherapy-naive pts (28 male and 17 female) with a median age of 60 years (range 35-74) were enrolled. 5-FU 2 g/m2 was given weekly over 24 h i.v. preceded by folinic acid 500 mg/m2 as a 2 h infusion. Paclitaxel 175 mg/m2 was administered as a 3 h-infusion on days 1 and 22 and cisplatin 50 mg/m2 as 1 h infusion on days 8 and 29. Six weeks of therapy (days 1, 8, 15, 22, 29, 36) followed by 2 weeks rest were considered one cycle. A median of 3 cycles (range 1-4) were administered to 45 pts assessable for response, survival and toxicity. Five pts (11%) obtained a CR and 18 pts (40%) a PR (ORR 51%; 95% CI: 35.8-66.3%). Responses were achieved in the liver, lymph nodes, lungs and at the site of the primary tumour. Nine pts (20%) had stable disease. Thirteen pts (29%) were considered to have failed treatment, 8 pts (18%) due to progressive disease and 5 pts (11%) who did not receive one complete cycle of therapy due to acute non-haematologic toxicity. The median progression-free and overall survival times were 9 months (range 1-36+) and 14 months (range 2-36+), respectively. Neutropenia WHO III(o)/IV(o) occurred in 7 pts (15%) with only 1 pt having grade IV. Additional non-haematologic WHO III(o)/IV(o) toxicities included nausea/vomiting in 5 (11%), alopecia in 22 (49%), and diarrhoea in 1 patient each (2%). Dose reductions or treatment delays were necessary in 8 pts (17%), mainly due to neutropenia. All pts were treated on an outpatient basis. The combination of paclitaxel, cisplatin and continuously infused 5-FU/folinic acid appears to be a highly active regimen for the treatment of pts with advanced gastric cancer. While the overall acceptable toxicity allows its use in the palliative setting, it may also be an attractive option to be tested for neoadjuvant or adjuvant treatment.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Paclitaxel; Peritoneal Neoplasms; Stomach Neoplasms; Survival Analysis

In this Phase I study, the maximally tolerated doses (MTDs) of i.p. iododeoxyuridine (IdUrd) alone and in combination with i.v. calcium leucovorin (LV) were determined. The pharmacokinetics and pharmacological advantage of IdUrd were evaluated, and flow cytometric analysis allowed examination of the extent of incorporation of IdUrd into tumor cells with and without the addition of i.v. LV. Thirty-nine patients with advanced neoplasms primarily confined to the peritoneal space were enrolled in a dose-escalation trial using 4-h dwells of IdUrd administered i.p. daily for 4 days with and without an i.v. infusion of LV 500 mg/m2/day for 4.5 days. Twenty-three patients received single-agent therapy, and 13 patients received i.p. IdUrd in combination with i.v. LV. The MTD of single-agent IdUrd administered on this schedule was 4125 mg/m2/day for 4 days; and that of the IdUrd in combination was 3438 mg/m2/day. Dose-limiting toxicities were myelosuppression and stomatitis. During the period of the dwell, the peritoneal AUC (area under the curve) of IdUrd exceeded the plasma AUC of IdUrd by one or two orders of magnitude in all patients at all doses tested; there was a possible effect of LV on peritoneal AUC. The geometric mean pharmacological advantage (AUCperitoneal/ AUCplasma) was 181 at 625 mg/m2/day and 90 at 4538 mg/m2/day. Flow cytometric analysis suggests saturation of IdUrd measured in DNA at the 2500-3125 mg/m2 dose level, without an increase after the addition of LV. Twelve patients received 4-12 courses of therapy. One patient with recurrent ovarian cancer who received 16 courses of therapy experienced complete resolution of her ascites, near normalization of CA-125 levels, and improved quality of life; two patients with high-risk tumors receiving "adjuvant" therapy are disease-free at 3 and 6 years after treatment; other patients experienced transient clearing of ascites. The recommended Phase II dose of i.p. IdUrd using a 4-h dwell daily for 4 days is 3750 mg/m2/day alone or 3125 mg/m2/day in combination with continuous i.v. LV at 500 mg/m2/day for 4.5 days. Although flow cytometric data suggest that DNA incorporation of IdUrd is not affected by the addition of LV, the cytotoxicity of the combination regimen may be increased due to LV-enhanced, IdUrd-related inhibition of thymidylate synthase. For this reason, we recommend that efficacy studies of the combination continue in parallel with studies of IdUrd alone.

Topics: Adult; Aged; Antidotes; Antimetabolites, Antineoplastic; CA-125 Antigen; DNA, Neoplasm; Drug Administration Schedule; Drug Therapy, Combination; Female; Gastrointestinal Neoplasms; Humans; Idoxuridine; Injections, Intraperitoneal; Injections, Intravenous; Leucovorin; Male; Middle Aged; Ovarian Neoplasms; Pancreatic Neoplasms; Peritoneal Neoplasms

Intraperitoneal (IP) administration of fluorinated pyrimidines has been evaluated for ovarian and gastrointestinal malignancies in phase I, II, and III trials. The tolerance and pharmacokinetic profile of IP 5-fluoro-2'-deoxyuridine(FUDR) alone and with (R,S)-leucovorin ((R,S)-LV) have each been evaluated in previous phase I studies. FUDR doses of 3 g per day with and without (R,S)-LV doses up to 640 mg per day given IP are well tolerated. The current phase I study was designed to determine the pharmacokinetic profiles and clinical tolerance of escalating doses of the pure biologically active S-isomer of leucovorin ((S)-LV) given IP with the same dosing schedule of FUDR. A group of 16 patients with disease confined to the abdominal cavity were treated in this study. Pharmacokinetic studies of blood and peritoneal fluid, toxicity profiles, and clinical response for the first three cycles are reported here. The toxicity profile did not significantly differ from the prior two studies. All non-hematologic toxicities, such as fatigue, nausea, vomiting, diarrhea, and abdominal discomfort were less than grade 4, and most were less than grade 3. Neutropenia and thrombocytopenia were uncommon and observed only in patients with compromised bone marrow reserve. The pharmacokinetic profiles were also congruent with the previous studies and indicate a three-log advantage for FUDR. The (S)-LV profiles in the peritoneal cavity paralleled those of FUDR. Antitumor effects or absence of progression until after cessation of therapy were documented in 11 patients. At a median follow-up of 18 months 44% of patients were alive. IP administration of 3-g of FUDR and up to 640 mg (S)-LV daily for three days was well tolerated. The tolerance and antitumor effects observed during IP FUDR and LV in these studies encourage further exploration of this regimen against ovarian and gastrointestinal malignancies. The actual role and optimal dose of LV as an enhancer of the antitumor actions of FUDR administered by this route remain unknown.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Female; Floxuridine; Humans; Injections, Intraperitoneal; Leucovorin; Male; Middle Aged; Peritoneal Neoplasms; Treatment Outcome

In a preceding study, we established the tolerance and pharmacokinetic behavior of 5-fluoro-2'-deoxyuridine (FdUrd) given by the intraperitoneal (IP) route. A dose of 3 g daily x 3 days was found satisfactory for Phase II study and exploration of biochemical modulation. Therefore, the current study was conducted to study the tolerance and pharmacokinetics of such a dose-schedule and route of FdUrd combined with escalating doses of leucovorin (LV). Fourteen patients were entered and 13 were evaluable for tolerance determination. Pharmacologic determinations of IP FdUrd and 5-Fluorouracil (FUra) derived from it and LV were obtained by HPLC methods on 11 occasions. Findings were compared with the preceding study of FdUrd alone. LV did not appear to alter the tolerance of IP FdUrd even in the four patients receiving the highest dose of LV (640 mg). Toxicities included nausea, vomiting, and rarely neutropenia and diarrhea. Pharmacokinetic parameters indicate a parallel rate of egress of FdUrd and LV from the peritoneal cavity. The pharmacologic advantage for FdUrd is at least 3 logs as previously reported and one log for LV. Evidence of antitumor effect was noted particularly among untreated patients with gastrointestinal primaries. We conclude that IP FdUrd 3 g and LV in doses of up to 640 mg x 3 days are well tolerated. Since FdUrd is more potent, has an even greater hepatic clearance and shows greater potential for modulation with LV than FUra, it may be the preferred fluoropyrimidine for subsequent studies via the IP route in the treatment of carcinomas with prominent peritoneal spread. The pharmacologic advantage for leucovorin is limited but it is a good marker for peritoneal clearance since it parallels FdUrd clearance.

Topics: Abdominal Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Female; Floxuridine; Half-Life; Humans; Infusions, Parenteral; Leucovorin; Male; Metabolic Clearance Rate; Peritoneal Neoplasms

This retrospective multicenter cohort study compared the feasibility and safety of oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy (PIPAC-Ox) with or without intraoperative intravenous 5-fluorouracil (5-FU) and leucovorin (L).. Our study included consecutive patients with histologically proven unresectable and isolated colorectal peritoneal metastases (cPM) treated with PIPAC-Ox in seven tertiary referral centers between January 2015 and April 2020. Toxicity events and oncological outcomes (histological response, progression-free survival, and overall survival) were compared between patients who received intraoperative intravenous 5-FU/L (PIPAC-Ox + 5-FU/L group) and patients who did not (PIPAC-Ox group).. In total, 101 patients (263 procedures) were included in the PIPAC-Ox group and 30 patients (80 procedures) were included in the PIPAC-Ox + 5-FU/L group. Common Terminology Criteria for Adverse Events v4.0 grade 2 or higher adverse events occurred in 48 of 101 (47.5%) patients in the PIPAC-Ox group and in 13 of 30 (43.3%) patients in the PIPAC-Ox + 5-FU/L group (p = 0.73). The complete histological response rates according to the peritoneal regression grading score were 27% for the PIPAC-Ox + 5-FU/L group and 18% for the PIPAC-Ox group (p = 0.74). No statistically significant differences were observed in overall or progression-free survival between the two groups.. The safety and feasibility of PIPAC-Ox + 5-FU/L appears to be similar to the safety and feasibility of PIPAC-Ox alone in patients with unresectable cPM. Oncological outcomes must be evaluated in larger studies.

Topics: Aerosols; Cohort Studies; Colorectal Neoplasms; Feasibility Studies; Fluorouracil; Humans; Leucovorin; Oxaliplatin; Peritoneal Neoplasms

We report a cases report of colorectal cancer who underwent repeated resection for peritoneal recurrences by laparoscopic surgery. In 2013, a 70-year-old woman diagnosed with an ascending colon cancer underwent laparoscopic right hemicolectomy. The pathological diagnosis was tub2, pT4aN1M0, Stage Ⅲb. Postoperative adjuvant chemotherapy(uracil and tegafur/Leucovorin)was administered. PET-CT performed at 25 months after the surgery because of CEA elevation. It revealed a peritoneal recurrence in the pouch of Douglas. The following peritoneal recurrences were removed by laparoscopic Hartmann's procedure. Chemotherapy(5-fluorouracil/levofolinate/oxaliplatin/bevacizumab)was administered 11 courses and after that chemotherapy(5-fluorouracil/levofolinate/bevacizumab)was administered 6 courses. PET-CT performed 37 months after the second surgery revealed a peritoneal recurrence near the right ovary in the pouch of Douglas. The following peritoneal recurrences was removed. Chemotherapy(tegafur/gimeracil/oteracil/bevacizumab)was administered 11 courses. The long-term survival has been continued for 7 years and 7 months after first operation. It was considered that laparoscopic surgery for peritoneal recurrence in colorectal cancer is contributed to one of the surgical procedures in selected patients.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colonic Neoplasms; Colorectal Neoplasms; Female; Fluorouracil; Humans; Laparoscopy; Leucovorin; Peritoneal Neoplasms; Positron Emission Tomography Computed Tomography; Recurrence; Tegafur

Numerous studies have suggested benefit for heated intraperitoneal chemotherapy (HIPEC) in the treatment of peritoneal metastases from colon cancer. However, the PRODIGE 7 trial that randomized 265 colon cancer patients to surgery plus HIPEC vs. surgery alone after neoadjuvant chemotherapy (NACT) did not confirm benefit. These data were published as an abstract and not as a peer-reviewed manuscript. One concern is that prior drug exposure may select for drug resistance and blunt HIPEC efficacy.. A database query identified colon cancer specimens evaluated for chemotherapy sensitivity by ex-vivo analysis of programmed cell death (EVA/PCD), a primary culture platform that examines drug-induced cell death (apoptotic & non-apoptotic) by morphologic, metabolic and histologic endpoints.. Of 87 fresh colon cancer specimens, 54 (62%) were untreated and 33 (38%) had received prior folinic acid, 5-fluorouracil, oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (CAPOX). In an apoptosis assay, the lethal concentration of 50% (LC50) in untreated patients was significantly lower than in patients treated by FOLFOX (p = 0.002). Then to approximate PRODIGE 7, treated patients were separated by having received oxaliplatin treatment less than or greater than 2 months before EVA/PCD analysis. The degree of resistance increasing significantly for patients who received treatment less than 2 months prior to EVA/PCD (p < 0.002). Activity for mitomycin and irinotecan was not significantly different for untreated vs. treated patients, but 5-FU was more resistant (P = 0.048).. The failure of PRODIGE 7 to improve survival with surgery plus HIPEC following NACT may reflect diminished oxaliplatin cytotoxicity in patients whose residual disease has been selected for oxaliplatin and 5-FU resistance.

Topics: Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Capecitabine; Colorectal Neoplasms; Drug Resistance, Neoplasm; Fluorouracil; Humans; Hyperthermic Intraperitoneal Chemotherapy; Irinotecan; Leucovorin; Mitomycin; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms; Primary Cell Culture; Tumor Cells, Cultured

Topics: Colorectal Neoplasms; Cytoreduction Surgical Procedures; Humans; Hyperthermic Intraperitoneal Chemotherapy; Leucovorin; Peritoneal Neoplasms

Topics: Colorectal Neoplasms; Cytoreduction Surgical Procedures; Humans; Hyperthermic Intraperitoneal Chemotherapy; Leucovorin; Peritoneal Neoplasms

Topics: Colorectal Neoplasms; Cytoreduction Surgical Procedures; Humans; Hyperthermic Intraperitoneal Chemotherapy; Leucovorin; Peritoneal Neoplasms

Topics: Colorectal Neoplasms; Cytoreduction Surgical Procedures; Humans; Hyperthermic Intraperitoneal Chemotherapy; Leucovorin; Peritoneal Neoplasms

Topics: Colorectal Neoplasms; Cytoreduction Surgical Procedures; Humans; Hyperthermic Intraperitoneal Chemotherapy; Leucovorin; Peritoneal Neoplasms

Pseudomyxoma peritonei (PMP) is a rare malignancy, and there is insufficient evidence about systemic chemotherapy for this disease.. We retrospectively evaluated the efficacy and safety of a chemotherapeutic regimen with 5-fluorouracil and oxaliplatin (modified FOLFOX6, mFOLFOX6) for patients with unresectable pseudomyxoma peritonei. Patients who received the therapy between April 2000 and February 2019 at the Department of Medical Oncology, Tohoku University Hospital, were enrolled in this study.. Eight patients were treated with mFOLFOX6. The sites of primary tumor were appendix in six patients, ovary in a patient, and urachus in a patient. Six patients received surgery. Seven patients had histologically high-grade PMP, and one patient had low-grade PMP. The median follow-up duration was 27.2 months. All the patients had non-measurable regions as the targets of tumor response. Non-complete response or non-progressive disease was observed in seven patients, with a disease control rate of 87.5%. The median progression-free survival and overall survival were 13.0 months and 27.9 months, respectively. An obvious reduction in the symptoms was observed in two patients. Five patients experienced decline in the serum tumor markers, CEA or CA19-9. The grade 3/4 toxicity that was observed was grade 4 neutropenia in one patient and grade 3 neutropenia in two patients.. mFOLFOX6 might be an effective and tolerable treatment option for patients with unresectable PMP. To our knowledge, this is the first case series of mFOLFOX6 in patients with unresectable PMP and the first case series of systemic chemotherapy for Asian patients with unresectable PMP.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; CA-19-9 Antigen; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Peritoneal Neoplasms; Progression-Free Survival; Pseudomyxoma Peritonei; Retrospective Studies; Treatment Outcome

Basic and clinical studies on small bowel adenocarcinoma (SBA) are limited due to the rare nature of this cancer. We established a patient-derived xenograft (PDX) model from the tumor tissue of an advanced SBA patient with liver and peritoneal metastasis, and a cell line from the PDX. In the PDX model, compared to the control group, 5-fluorouracil (5-FU) treatment resulted in statistically significant tumor growth inhibition (TGI), while oxaliplatin (OHP) and irinotecan had no significant inhibitory effects. In combination with 5-FU, OHP showed the highest rate of TGI. The IC

Topics: Adenocarcinoma; Aged; Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cell Line, Tumor; Cell Proliferation; Deoxycytidine; Drug Evaluation, Preclinical; Female; Fluorouracil; Gemcitabine; Heterografts; HT29 Cells; Humans; Inhibitory Concentration 50; Irinotecan; Jejunal Neoplasms; Leucovorin; Liver Neoplasms; Mice; Mice, Nude; Neoplasm Transplantation; Organoplatinum Compounds; Oxaliplatin; Paclitaxel; Peritoneal Neoplasms; Treatment Failure; Trifluridine; Xenograft Model Antitumor Assays

This study aimed to evaluate the efficacy and the safety of polyethylene glycol conjugated granulocyte colony-stimulating factor (PEG-G-CSF) for preventing neutropenia in metastatic colorectal cancer (mCRC) patients that received fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus bevacizumab (Bev) in clinical practice.. We retrospectively analyzed mCRC patients who received FOLFOXIRI plus Bev between December 2015 and December 2017. We evaluated the efficacy of PEG-G-CSF as preventing or treating grade 3 or 4 neutropenia, the overall response rate (ORR) according to the Response Evaluation Criteria in Solid Tumors version 1.1, progression-free survival (PFS), overall survival (OS), and adverse events of FOLFOXIRI plus Bev based on the Common Terminology Criteria for Adverse Events version 4.0.. A total of 26 patients (median age 53.5 years) were included. The ORR rate was 65.3%, the median PFS was 9.6 months (7.2-16.9), and the median OS was 24.2 months (13.6-NA). Grade 3 or 4 neutropenia occurred in 53.8% of the patients, and febrile neutropenia occurred in 7.7%. PEG-G-CSF was given to 77.0% of the patients, including prophylactically (n = 9) and after the development of grade 3 or 4 neutropenia (n = 11). No patients experienced grade 3 or 4 neutropenia after the administration of PEG-G-CSF. In seven of the nine patients who received PEG-G-CSF prophylactically (77.8%), no dose adjustment was required.. PEG-G-CSF is useful in preventing severe neutropenia in mCRC patients treated with FOLFOXIRI plus Bev.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colorectal Neoplasms; Female; Fluorouracil; Follow-Up Studies; Granulocyte Colony-Stimulating Factor; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neutropenia; Oxaliplatin; Peritoneal Neoplasms; Polyethylene Glycols; Prognosis; Retrospective Studies; Survival Rate

This study evaluated the histologic response after preoperative systemic therapy (pST) using the Peritoneal Regression Grading Score (PRGS) and tumor regression grade (TRG) classifications for patients with peritoneal metastases (PM) from colorectal cancer (CRC).. Twenty-three patients were selected from a prospective database of 196 patients who underwent CRS followed by HIPEC for synchronous PM from CRC. In all study patients, biopsies of the PM obtained before pST (during the first laparoscopy) and after pST (during cytoreductive surgery) were compared.. Complete (PRGS 1), Major (PRGS 2), Minor (PRGS 3) and no histological responses (PRGS 4) were obtained in 17,5%, 52% and 13% and 17,5% of patients, respectively. Major (TRG 1-2), partial (TRG3), and no (TRG4-5) histological tumor regression were observed in 61%, 9% and 30% of patients, respectively. Regardless of the classification applied, median OS was significantly higher in patients with a "complete or major" response than in those with a "minor/partial or no" response (54 vs. 26 months, p < 0.05).. The PRGS and TRG can be used in clinical practice to evaluate the histological response after pST. This study demonstrated that a complete histologic response of PM from CRC can be obtained after pST.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Cetuximab; Colorectal Neoplasms; Cytoreduction Surgical Procedures; Disease-Free Survival; Female; Fluorouracil; Humans; Hyperthermic Intraperitoneal Chemotherapy; Leucovorin; Male; Neoadjuvant Therapy; Organoplatinum Compounds; Peritoneal Neoplasms; Proportional Hazards Models

A male patient in his 80s, diagnosed with rectal cancer, underwent transverse colon resection(pT3, pN0, cM0, and pStage Ⅱa, RAS wild-type, BRAF-mutant). However, 19 months later, intraperitoneal metastasis was detected and the patient received 8 courses of mFOLFOX6 plus bevacizumab. Following the observation of an allergic reaction that was attributable to oxaliplatin, the regimen was changed to a total of 7 courses of sLV5FU2 plus bevacizumab. Subsequently, a marked decrease was observed in intraperitoneal metastasis. The patient completed sLV5FU2 plus bevacizumab chemotherapy. At 1 year after the marked decrease, the metastatic recurrence was not exacerbated.

Topics: Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colon, Transverse; Colonic Neoplasms; Fluorouracil; Humans; Leucovorin; Male; Organoplatinum Compounds; Peritoneal Neoplasms

To date, there are no data on the value of adjuvant systemic chemotherapy following up-front resection of isolated synchronous colorectal peritoneal metastases.. To assess the association between adjuvant systemic chemotherapy and overall survival following up-front resection of isolated synchronous colorectal peritoneal metastases.. In this population-based, observational cohort study using nationwide data from the Netherlands Cancer Registry (diagnoses between January 1, 2005, and December 31, 2017; follow-up until January 31, 2019), 393 patients with isolated synchronous colorectal peritoneal metastases who were alive 3 months after up-front complete cytoreductive surgery with hyperthermic intraperitoneal chemotherapy were included. Patients allocated to the adjuvant systemic chemotherapy group were matched (1:1) with those allocated to the active surveillance group by propensity scores based on patient-, tumor-, and treatment-level covariates.. Adjuvant systemic chemotherapy, defined as systemic chemotherapy without targeted therapy, starting within 3 months postoperatively.. Overall survival was compared between matched groups using Cox proportional hazards regression analysis adjusted for residual imbalance. A landmark analysis was performed by excluding patients who died within 6 months postoperatively. A sensitivity analysis was performed to adjust for unmeasured confounding by major postoperative morbidity.. Of 393 patients (mean [SD] age, 61 [10] years; 181 [46%] men), 172 patients (44%) were allocated to the adjuvant systemic chemotherapy group. After propensity score matching of 142 patients in the adjuvant systemic chemotherapy group with 142 patients in the active surveillance group, adjuvant systemic chemotherapy was associated with improved overall survival compared with active surveillance (median, 39.2 [interquartile range, 21.1-111.1] months vs 24.8 [interquartile range, 15.0-58.4] months; adjusted hazard ratio [aHR], 0.66; 95% CI, 0.49-0.88; P = .006), which remained consistent after excluding patients who died within 6 months postoperatively (aHR, 0.68; 95% CI, 0.50-0.93; P = .02) and after adjustment for major postoperative morbidity (aHR, 0.71; 95% CI, 0.53-0.95).. Findings of this study suggest that in patients undergoing up-front resection of isolated synchronous colorectal peritoneal metastases, adjuvant systemic chemotherapy appeared to be associated with improved overall survival. Although randomized trials are needed to address the influence of potential residual confounding and allocation bias on this association, results of this study may be used for clinical decision-making in this patient group for whom no data are available.

Topics: Aged; Antineoplastic Agents; Capecitabine; Chemotherapy, Adjuvant; Colorectal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Oxaliplatin; Peritoneal Neoplasms; Watchful Waiting

Peritoneal cancer index (PCI) >20 is often seen as a contraindication for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal metastases (PM) from colorectal cancer. The aim of this study was to compare the overall survival in colorectal PM patients with PCI >20 and PCI ≤20 treated with CRS and HIPEC to those having open-close/debulking procedure only.. All patients with colorectal PM and intention to treat with CRS and HIPEC in Uppsala Sweden 2004-2017 were included. Patients scheduled for CRS and HIPEC were divided into three groups, PCI >20, PCI ≤20, and those not operated with CRS and HIPEC stated as open-close including those treated with palliative debulking.. Of 201 operations, 112 (56%) resulted in CRS and HIPEC with PCI ≤20, 45 (22%) in CRS and HIPEC with PCI >20 and 44 (22%) resulted in open-close/debulking. Median survival for CRS and HIPEC and PCI >20 was 20 months (95%CI 14-27 months) with 7% surviving longer than 5 years (n = 3). For CRS and HIPEC and PCI ≤20 the median survival was 33 months (95%CI 30-39 months) with 23% (n = 26) surviving >5years. The median survival for open-close was 9 months (95%CI 4-10 months), no one survived >5years.. Patients with PM from colorectal cancer and PCI >20 that were treated with CRS and HIPEC experience a one year longer and doubled overall survival compared with open-close/debulking patients. In addition to PCI, more factors should be taken into account when a decision about proceeding with CRS or not is taken.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Administration, Intravenous; Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Signet Ring Cell; Colorectal Neoplasms; Cytoreduction Surgical Procedures; Female; Fluorouracil; Humans; Hyperthermic Intraperitoneal Chemotherapy; Leucovorin; Male; Middle Aged; Oxaliplatin; Peritoneal Neoplasms; Retrospective Studies; Survival Rate; Young Adult

By using the Korean Pancreatic Cancer (K-PaC) registry, we compared the clinical outcomes of FOLFIRINOX (FFX) and gemcitabine plus nab-paclitaxel (GNP) in patients with metastatic pancreatic cancer (MPC).. We constructed a web-based database of 3748 anonymized patients diagnosed with pancreatic ductal adenocarcinoma. MPC patients who received first-line FFX or GNP were enrolled. Overall survival (OS), progression-free survival, grade III to IV toxicity, and cross-over treatment were analyzed.. A total of 413 patients (232 vs. 181, FFX vs. GNP; all data are presented in this sequence) were eligible. Median age was 63 years (60 vs. 69 y) with 43% (39% vs. 47%) comprising female individuals. The major metastatic sites were the liver (64%), peritoneum (25%), and distant lymph nodes (18%). The median OS was 11.5 versus 12.7 months (hazard ratio [HR]=0.87, 95% confidence interval [CI]: 0.68-1.12, P=0.286), and median progression-free survival was 7.5 versus 8.1 months (HR=0.92, 95% CI: 0.70-1.20, P=0.517), respectively. The frequency of grade III to IV febrile neutropenia was higher in the FFX group (18% vs. 11%, P=0.040), and that of peripheral neuropathy was higher in the GNP group (8% vs. 14%, P=0.046). The chance to receive second-line chemotherapy was higher in the GNP group (45% vs. 56%, P=0.036). In the cross-over treatment, the median OS of the FFX-GNP group (n=43) and the GNP-FFX group (n=47) was 16.8 versus 17.7 months (HR=0.79, 95% CI: 0.44-1.41, P=0.425).. FFX and GNP showed similar efficacy and comparable toxicity in MPC patients. Although the GNP group had a higher chance to receive second-line chemotherapy, they did not have improved overall survival.

Topics: Aged; Albumins; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; Cross-Over Studies; Deoxycytidine; Febrile Neutropenia; Female; Fluorouracil; Gemcitabine; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Oxaliplatin; Paclitaxel; Pancreatic Neoplasms; Peripheral Nervous System Diseases; Peritoneal Neoplasms; Progression-Free Survival; Registries; Republic of Korea; Survival Rate; Treatment Outcome

Topics: Colorectal Neoplasms; Humans; Hyperthermia, Induced; Leucovorin; Peritoneal Neoplasms; Second-Look Surgery

Topics: Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Peritoneal Neoplasms; Retrospective Studies

Peritoneal carcinomatosis (pcm) in metastatic pancreatic ductal adenocarcinomas (mpdac) is frequently encountered in day-to-day practice, but rarely addressed in the literature. The objective of the present study was to describe the management and outcome of patients diagnosed with pcm.. Data for all consecutive patients with mpdac treated in our centre between 1 January 2014 and 31 August 2015 were analyzed retrospectively. Computed tomography imaging was centrally reviewed by a dedicated radiologist to determine the date of pcm diagnosis.. The analysis included 48 patients. Median age in the group was 61 years, and 41 patients had an Eastern Cooperative Oncology Group performance status (ecog ps) of 0-1. All patients presented with pcm either synchronously (group 1) or metachronously (group 2). Those groups differed significantly by baseline ecog ps and neutrophil-to-lymphocyte ratio (nlr), with ecog ps being poorer and nlr being higher in group 1. In addition to pcm, the main sites of metastasis were liver (62.5%) and lungs (31.3%). First-line chemotherapy in 36 patients (75%) was folfirinox (fluorouracil-irinotecan-leucovorin-oxaliplatin). The median overall survival for the entire population was 10.81 months [95% confidence interval (ci): 7.16 months to 14.16 months]; it was 13.17 months (95% ci: 5.9 months to 15.4 months) for patients treated with folfirinox. Median overall survival was 7.13 months (95% ci: 4.24 months to 10.41 months) for patients in group 1 and 14.34 months (95% ci: 9.79 months to 19.91 months) for patients in group 2,. Compared with other metastatic sites, synchronous pcm seems to be a poor prognostic factor. It could be more frequently associated with a poor ecog ps and a nlr greater than 5 in this group of patients. In patients with mpdac and pcm, either synchronous or metachronous, folfirinox remains an efficient regimen.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Oxaliplatin; Pancreatic Neoplasms; Peritoneal Neoplasms; Prognosis; Retrospective Studies; Survival Analysis; Tomography, X-Ray Computed; Treatment Outcome

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) has become standard of care for patients with peritoneal metastases of colorectal origin with a low/moderate abdominal disease load. In case of a peritoneal cancer index (PCI) score >20, CRS-HIPEC is not considered to be beneficial. Patients with a PCI >20 are currently offered palliative systemic chemotherapy. Previous studies have shown that systemic chemotherapy is less effective against peritoneal metastases than it is against haematogenous spread of colorectal cancer. It is suggested that patients with peritoneal metastases may benefit from the addition of intraperitoneal chemotherapy to systemic chemotherapy. Aim of this study is to establish the maximum tolerated dose of intraperitoneal irinotecan, added to standard of care systemic therapy for colorectal cancer. Secondary endpoints are to determine the safety and feasibility of this treatment and to establish the pharmacokinetic profile of intraperitoneally administered irinotecan.. This phase I, '3+3' dose-escalation, study is performed in two Dutch tertiary referral centres. The study population consists of adult patients with extensive peritoneal metastases of colorectal origin who have a good performance status and no extra-abdominal metastases. According to standard work-up for CRS-HIPEC, patients will undergo a diagnostic laparoscopy to score the PCI. In case of a PCI >20, a peritoneal access port will be placed in the abdomen of the patient. Through this port we will administer intraperitoneal irinotecan, in combination with standard systemic treatment consisting of 5-fluorouracil/leucovorin with oxaliplatin and the targeted agent bevacizumab. Therapy consists of a maximum of 12 cycles 2-weekly.. This study protocol is approved by a research medical ethics committee (Rotterdam, Netherlands) and the Dutch Competent Authority (CCMO, The Hague, Netherlands). The results of this trial will be submitted for publication in a peer-reviewed scientific journal.. NL6988 and NL2018-000479-33; Pre-results.

Topics: Antineoplastic Combined Chemotherapy Protocols; Clinical Trials, Phase I as Topic; Colorectal Neoplasms; Fluorouracil; Humans; Infusions, Parenteral; Irinotecan; Leucovorin; Multicenter Studies as Topic; Organoplatinum Compounds; Peritoneal Neoplasms; Research Design

A 33-year-old man was diagnosed with bowel obstruction due to advanced sigmoid colon cancer and underwent an emergency laparotomy. The sigmoid colon cancer turned out to be unresectable because of firm invasion to the retroperitoneum with severe adhesions and diffuse dissemination. Therefore, unplanned jejunostomy was performed, which was complicated by high-output stoma and short bowel syndrome. His condition was stable enough to receive chemotherapy via parenteral nutrition and parenteral electrolyte solution infusion added to the diet. mFOLFOX6 plus cetuximab therapy was started 4 weeks postoperatively. Although oxaliplatin was discontinued because of worsening numbness, he was sustained without cancer progression by receiving chemotherapy for a year. Chemotherapy was interrupted by a Candida fungemia 13months postoperatively, and he died 4 months later. Patients with jejunostomy may have difficulty absorbing enough water and nutrients in the intestine; therefore, they are at risk of dehydration and electrolyte depletions due to high stomal output, and malnutrition due to the short bowel. These complications may prevent colorectal cancer patients with jejunostomy to be indicated for chemotherapy.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cetuximab; Fluorouracil; Humans; Jejunostomy; Leucovorin; Male; Organoplatinum Compounds; Peritoneal Neoplasms; Short Bowel Syndrome; Sigmoid Neoplasms

Adenocarcinoma ex-goblet cell carcinoids (AGCCs) are rare appendiceal tumors with mixed neuroendocrine and glandular features. They tend to behave more aggressively than typical carcinoid tumors, affect younger patients, and have a greater predilection for spreading to the peritoneum. Outcomes of AGCC patients treated with chemotherapy, extrapolated from colon cancer regimens, in the adjuvant or metastatic setting have not been explicitly reported. We sought to explore outcomes of AGCC patients with either local disease treated with adjuvant FOLFOX or metastatic disease treated with FOLFOX/FOLFIRI post-cytoreductive debulking (or CRS plus HIPEC in the peritoneal-limited setting).. We performed a single-institution retrospective analysis of 23 pathologically identified AGCC patients from Vanderbilt University Medical Center treated with chemotherapy in either the adjuvant or metastatic settings. Each patient's tumor was categorized as group B or group C based on the criteria from Tang et al. Median progression-free survival (PFS) or disease-free survival (DFS) (in the curative setting) and overall survival (OS) were determined for each patient and specified patient subgroup.. AGCC patients who were treated with FOLFOX chemotherapy in the adjuvant setting or FOLFOX/FOLFIRI in the metastatic setting experienced prolonged PFS, DFS, and OS. Five patients with peritoneal-limited disease treated with CRS plus HIPEC have not yet reached median PFS or OS. While small sample size, patient selection, and retrospective nature limit the generalizability of findings from our analysis, the efficacy signals we observed suggest prospective evaluation with chemotherapy and CRS plus HIPEC is warranted in AGCC patients.

Topics: Antineoplastic Combined Chemotherapy Protocols; Appendiceal Neoplasms; Camptothecin; Carcinoid Tumor; Chemotherapy, Adjuvant; Cytoreduction Surgical Procedures; Disease-Free Survival; Female; Fluorouracil; Follow-Up Studies; Goblet Cells; Humans; Hyperthermia, Induced; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Peritoneal Neoplasms; Progression-Free Survival; Retrospective Studies

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Cecal Neoplasms; Chemotherapy, Adjuvant; Colectomy; Colorectal Neoplasms; Female; Fluorouracil; Humans; Hysterectomy; Laparoscopy; Leucovorin; Middle Aged; Peritoneal Neoplasms; Salpingo-oophorectomy; Vesicovaginal Fistula

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

Peritoneal carcinomatosis (PC) from colorectal cancer is associated with poor prognosis. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has improved survival for patients with colorectal peritoneal carcinomatosis. However, standardization of HIPEC protocols, including which chemotherapeutic agent to use, is lacking in the literature. Therefore, we sought to report survival outcomes from colorectal cancer patients undergoing CRS/oxaliplatin-based HIPEC at our institution over the last 10 years.. Colorectal PC patients treated with CRS/oxaliplatin-based HIPEC 2004-2015 were included. Demographic, clinical, and oncologic data were abstracted from the medical record. Overall (OS) and disease-free survival (DFS) were calculated using Kaplan-Meier analysis. Univariate/multivariate Cox regression analysis was done.. Laparotomy was performed in 113 patients for colorectal PC; 91 completed a curative intent CRS/HIPEC. At 3 and 5 years, OS for the CRS/HIPEC cohort was 75% and 55%, and DFS was 50% and 25%, respectively. On multivariate analysis, incremental increases in peritoneal carcinomatosis index (PCI) were associated with worse OS (p = 0.0001) and DFS (p = 0.0001). Grade III/IV complications were also associated with worse OS.. A standardized regimen of CRS and oxaliplatin-based HIPEC for colorectal PC is effective with favorable OS and DFS and acceptable complication rates.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Carcinoma; Chemotherapy, Cancer, Regional Perfusion; Colorectal Neoplasms; Combined Modality Therapy; Cytoreduction Surgical Procedures; Female; Fluorouracil; Follow-Up Studies; Humans; Hyperthermia, Induced; Irinotecan; Leucovorin; Male; Middle Aged; Oxaliplatin; Peritoneal Neoplasms; Prognosis; Prospective Studies; Retrospective Studies; Survival Rate

There is no standard first-line chemotherapy for advanced gastric cancer with severe peritoneal metastasis. Although fluoropyrimidine is often used, its efficacy is limited, and it remains unclear whether combination therapy with platinum improves clinical outcomes.. This retrospective study involved patients at six Japanese academic hospitals between 2010 and 2016. Patients with advanced gastric cancer and severe peritoneal metastasis were included if they had massive ascites and/or inadequate oral intake requiring intravenous nutritional support. We then compared the efficacy and safety of fluoropyrimidine monotherapy with those of fluoropyrimidine/platinum combination therapy.. Compared with the combination therapy group (n = 64), the monotherapy group (n = 65) had worse general health (more patients with elderly age, performance status > 2, and having both massive ascites and inadequate oral intake). Both overall survival (9.0 vs 5.0 months, p < 0.01) and progression-free survival (4.3 vs 2.3 months, p < 0.01) were significantly longer in the combination group, and the significance remained after adjusting for prognostic variables (hazard ratios of 0.47 and 0.41, respectively; p < 0.01). Improvements in ascites and oral intake were also greater in the combination group. Although neutropenia (grade ≥ 3) occurred more frequently with combination therapy, both treatments in this study were tolerable.. Combination therapy with fluoropyrimidine and platinum might be more effective than monotherapy with fluoropyrimidine and was tolerable for patients with advanced gastric cancer and severe peritoneal metastasis.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Ascites; Cisplatin; Drug Combinations; Female; Fluorouracil; Humans; Leucovorin; Male; Malnutrition; Methotrexate; Middle Aged; Neutropenia; Organoplatinum Compounds; Oxonic Acid; Peritoneal Neoplasms; Progression-Free Survival; Pyridines; Retrospective Studies; Stomach Neoplasms; Tegafur; Treatment Outcome; Withholding Treatment; Young Adult

Cytoreductive surgery including liver resection and hyperthermic intraperitoneal chemotherapy provide survival benefit to selected patients but is associated with relevant morbidity and mortality rates. We aimed to report morbidity and mortality rates and parameters linked to increased morbidity.. Retrospective analysis of 37 patients who underwent liver resection and cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy between 2006 and 2016. From a prospectively collected database the morbidity and mortality rates and survival data were analyzed.. The mortality rate was 0% and grade III-IV morbidity was 42%. Re-operation rate was 27%. Patients with complications tended to have a higher peritoneal cancer index (16 vs. 13; P=0.23). The performance of rectal resections was statistically significantly associated with morbidity (P=0.02). Neither performance of other type of resections nor the hyperthermic intraperitoneal chemotherapy compound nor the completeness of cytoreduction score was associated with elevated morbidity. No complications related to liver resections were observed. Furthermore, origin of peritoneal metastases did not impact on occurrence of complications. Median overall survival for colorectal primaries was 22 months (range, 9-60 months) and 30 months (range, 12-58 months) for ovarian cancer.. Simultaneous resection of hepatic and peritoneal metastases seems to provide a survival benefit for selected patients and is associated with acceptable morbidity and mortality rates. Knowledge of patients and operative factors linked to morbidity will help to provide a strict selection process and a safer surgical procedure.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Combined Modality Therapy; Cytoreduction Surgical Procedures; Female; Fluorouracil; Hepatectomy; Humans; Hyperthermia, Induced; Leucovorin; Liver Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Ovarian Neoplasms; Peritoneal Neoplasms; Retrospective Studies

We investigated bladder urothelial carcinoma with peritoneal involvement.. Inclusion criteria were: pathology-confirmed urothelial carcinoma; peritoneal spread identified on computed tomographic (CT) scans performed initially or after either cystectomy or concomitant chemoradiotherapy (CCRT), and absence of visceral metastases; and chemotherapy administered after peritoneal spread was diagnosed.. Forty-seven cases included initial modes of therapy with chemotherapy in 24 patients (51%), cystectomy in 17 (36%), and CCRT in six (13%), only given as a result of under-staging. After local therapy, these patients received a continuous maintenance chemotherapy regimen of 5-fluorouracil, leucovorin, cisplatin, and gemcitabine. The overall response rate was 85%, and the side-effects were mild and tolerated. The median survival time was 28 months. The survival time of cases initially treated only with chemotherapy was not statistically different to that of those with local disease.. Bladder urothelial carcinomas with peritoneal involvement can benefit from continuous maintenance chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Transitional Cell; Chemoradiotherapy; Cisplatin; Cystectomy; Deoxycytidine; Female; Fluorouracil; Gemcitabine; Humans; Leucovorin; Maintenance Chemotherapy; Male; Middle Aged; Peritoneal Neoplasms; Retrospective Studies; Survival Analysis; Treatment Outcome; Urinary Bladder Neoplasms

Severe peritoneal metastasis (PM) from advanced gastric cancer (AGC) causes massive ascites and inadequate oral intake. Because patients with severe PM are often not included in clinical trials, little is known regarding the efficacy and safety of oxaliplatin with l-leucovorin and bolus/continuous infusion of 5-fluorouracil (FOLFOX) for them.. We retrospectively studied AGC patients with massive ascites and/or inadequate oral intake due to severe PM treated with FOLFOX as the first-line treatment.. Only 39 (10%) of 378 AGC patients had severe PM; 10 received FOLFOX. The median progression-free and overall survivals were 7.5 and 13.2 months, respectively. Ascites decreased in seven of nine patients with ascites, and oral intake improved in four of seven patients with an inadequate oral intake. Common grade 3-4 adverse events included neutropenia and anemia.. This study suggests that FOLFOX is effective and manageable for AGC patients with severe PM.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms; Retrospective Studies; Stomach Neoplasms; Treatment Outcome

A 67-year-old woman was diagnosed with cecal cancer, para-aortic lymph node metastasis, peritoneum dissemination, and left breast cancer. We administered mFOLFOX6 plus panitumumab for cecal cancer and an aromatase inhibitor for her breast cancer. She received 7 courses of systemic chemotherapy and showed a partial response. She additionally received 5 courses of mFOLFOX6 plus panitumumab. We performed ileocecal resection, sigmoidectomy, right oophorectomy, dissection of the para-aortic lymph nodes, and peritoneal dissemination. The histopathological findings revealed adenocarcinoma, ypT3, ypN0, ycM0, ypStage II (therapeutic effect Grade 2). One month later, she underwent an enforced left breast segmental resection and sentinel lymph node biopsy(0/2). The results of the pathological examination indicated no residual cancers (therapeutic effect Grade 3). The patient is now in good health and was administered S-1 as an outpatient.

Topics: Aged; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Aorta; Cecal Neoplasms; Colectomy; Female; Fluorouracil; Humans; Leucovorin; Lymphatic Metastasis; Neoadjuvant Therapy; Organoplatinum Compounds; Panitumumab; Peritoneal Neoplasms

FOLFIRINOX is a first-line treatment option for patients with metastatic pancreatic cancer (MPC) and is associated with improved survival yet significantly more toxicities than standard gemcitabine. Our aim was to determine the proportion of patients with MPC who would be eligible for FOLFIRINOX based upon the pivotal ACCORD study criteria.. Patients with confirmed MPC at the time of referral to the BC Cancer Agency between 2004 and 2007 were identified from the Gastrointestinal Cancers Outcomes Unit Database (GICOU). Proportion of patients that met the ACCORD study eligibility criteria was determined by chart review. Criteria for FOLFIRINOX exclusion were assessed using descriptive statistics.. A total of 100 consecutive patients with complete chart records and MPC were identified. Fifty-two (52%) were male and the median age was 68 years (range, 42 to 98 y). The most common sites of metastases were liver (63%) and peritoneum (22%). Only 26 patients fulfilled the ACCORD study eligibility criteria. The most common reasons for FOLIFIRINOX exclusion per ACCORD were poor Eastern Cooperative Oncology Group score of ≥2 (64%), age of 76 years or greater (22%), elevated bilirubin (22%), and inadequate renal function (6%).. Despite the proven survival benefit of FOLFIRINOX, only approximately one quarter of patients in the real-world setting with MPC would have been considered eligible for such therapy based upon the ACCORD eligibility criteria. Careful patient selection and more tolerable therapies are required.

Topics: Activities of Daily Living; Adenocarcinoma; Adult; Age Factors; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; British Columbia; Camptothecin; Eligibility Determination; Female; Fluorouracil; Humans; Hyperbilirubinemia; Irinotecan; Leucovorin; Liver Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Pancreatic Neoplasms; Peritoneal Neoplasms; Renal Insufficiency; Retrospective Studies

Peritoneal carcinomatosis (PC) from colorectal cancers (CRC) either at initial presentation or at subsequent recurrence presents a significant treatment challenge. The aim of our study was to find its incidence and analyze outcomes of patients with PC from CRC origin managed by different treatment modalities.. A retrospective analysis of patients, from August 2013 to July 2014, presenting with metastatic peritoneal disease from CRC with or without metastasis to other sites was performed. PC was classified as limited (peritoneal carcinomatosis index [PCI] < 10) and widespread (PCI > 10).. This study included 70 patients; 45 patients had peritoneum as the only site of metastasis and the remaining 25 visceral metastasis with peritoneum. Resections were performed in 23 patients (19 underwent R0 resection and 4 were R+). All patients received systemic chemotherapy (FOLFOX [Oxaliplatin with fluorouracil and folinic acid]/CAPOX [oxaliplatin and capecitabine]). At a median follow-up of 11 months, the median OS was 14 months. Patients with PCI < 10 had significantly better survival (median not reached) as compared with those with PCI > 10 (15 months). Patients undergoing R0 resection had better survival (24 months) versus those with R+ resection (16 months). The survival of patients receiving only systemic chemotherapy was 11 months.. The incidence of peritoneal metastasis in CRC is about 10%. A select group of patients who have low PCI who undergo R0 resection of only the diseased portion, without entire peritonectomy, still do well. Where facilities for hyperthermic intraperitoneal chemotherapy are not available, cytoreduction followed by systemic chemotherapy should be considered. The added role of hyperthermic intraperitoneal chemotherapy in this subgroup needs to be evaluated.

Topics: Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Colorectal Neoplasms; Combined Modality Therapy; Cytoreduction Surgical Procedures; Female; Fluorouracil; Follow-Up Studies; Humans; Hyperthermia, Induced; Incidence; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms; Retrospective Studies; Survival Rate

Intraperitoneal chemotherapy has an established role in the treatment of selected patients with colorectal peritoneal metastases. Oxaliplatin is highly suitable as a chemotherapeutic agent for hyperthermic intraperitoneal chemotherapy (HIPEC), but its use to date has been limited because of the morbidity caused by severe electrolyte and glycemic imbalances associated with 5% glucose as its carrier solution. This report provides an overview of the development, rationale, and application of intraperitoneal chemotherapy and the use of various drugs and carrier solutions. A novel, evidence-based protocol for bidirectional oxaliplatin-based HIPEC in a physiologic carrier solution (Dianeal PD4 dextrose 1.36%) is presented, and its impact on electrolyte and glucose levels is demonstrated.. After implementation of the new protocol, the serum electrolyte (sodium, potassium, and chloride) levels, glucose levels, and intravenous insulin requirements were intensively measured in eight consecutive cases immediately before HIPEC (T = 0), immediately after HIPEC (T = 30), 1 h after HIPEC (T = 60), and 3 h after HIPEC (T = 180).. The median sodium levels were 140 mmol/L at T = 0, 138 mmol/L at T = 30, 140 mmol/L at T = 60, and 140 mmol/L at T = 180. The respective median potassium levels were 4.6, 4.2, 3.7, and 3.9 mmol/L, and the respective median chloride levels were 112, 111, 111, and 112 mmol/L. The respective median glucose levels were 9, 11.5, 10.7, and 8.6 mmol/L. The median insulin requirements were respectively 0.5, 1.5, 1.2, and 0 U/h. None of the patients were diabetic.. Using a novel protocol for bidirectional oxaliplatin-based HIPEC in Dianeal instead of 5% glucose, the observed fluctuations in this study were minimal and not clinically relevant compared with historical values for electrolyte and glycemic changes using 5% glucose as a HIPEC carrier solution. This novel protocol leads to only minimal and clinically irrelevant electrolyte and glycemic disturbances, and its adoption as the standard protocol for oxaliplatin-based HIPEC should be considered.

Topics: Administration, Intravenous; Antineoplastic Combined Chemotherapy Protocols; Blood Glucose; Chlorides; Colorectal Neoplasms; Cytoreduction Surgical Procedures; Dialysis Solutions; Evidence-Based Medicine; Female; Fluorouracil; Humans; Hyperthermia, Induced; Infusions, Parenteral; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms; Potassium; Sodium

Pseudomyxoma peritonei is a disease that results from a perforated mucinous neoplasm of the appendix so that mucinous ascites and mucin-producing tumor cells are widely disseminated in a characteristic pattern throughout the abdomen and pelvis. The intraabdominal mucus can accumulate in the inguinal canal and by physical examination be indistinguishable from the usual inguinal hernia.. A database of patients with pseudomyxoma peritonei was used to identify patients who had an inguinal hernia prior to or at the time of cytoreductive surgery (CRS) and perioperative hyperthermic chemotherapy (HIPEC). At the time of CRS, care was taken in all patients to remove the peritoneal lining of the inguinal canal. Patients who had the inguinal hernia repaired prior to definitive treatment with CRS and HIPEC had all tissue and mesh associated with prior herniorrhaphy resected.. In 178 pseudomyxoma peritonei patients, 17 had a new onset or previously repaired inguinal hernia that required extraction of mucus and mucinous tumor from the hernia site. No repair of the open inguinal canal was attempted at the time of CRS. No recurrent inguinal hernias were recorded and no patients required an inguinal incision at a later time to resect progressive disease within the inguinal canal.. Inguinal hernias caused by mucinous ascites and tumor were definitively treated by cytoreductive surgery plus HIPEC. Extraction of tumor and peritoneum from the inguinal canal facilitates fibrous closure of the hernia defect so that hernia recurrence was not observed.

Topics: Adenocarcinoma, Mucinous; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Appendiceal Neoplasms; Ascites; Cytoreduction Surgical Procedures; Doxorubicin; Female; Fluorouracil; Hernia, Inguinal; Humans; Hyperthermia, Induced; Infusions, Parenteral; Inguinal Canal; Leucovorin; Male; Middle Aged; Mitomycin; Mucus; Peritoneal Neoplasms; Pseudomyxoma Peritonei; Retrospective Studies; Tomography, X-Ray Computed

The aim of this study is to discuss the curative effect of introperitoneal hyperthermic perfusion chemotherapy(IHPC) combined with systemic neoadjuvant chemotherapy on the gastric cancer patients with peritoneal carcinomatosis.. Sixty-four patients with gastric cancer and peritoneal carcinomatosis who were hospitalized in the Department of Gastrointestinal Surgery of First Hospital of Jilin University from December 2006 to December 2013. After peritoneal carcinomatosis was confirmed during laparoscopic exploration, FOLFOX6 (oxaliplatin and calcium folinate and 5-Fu) was performed for systemic chemotherapy. One course was 14 days and a complete treatment includes four courses. At the same time, patients underwent peritoneal catheter insertion and received IHPC(5-Fu 1 500 mg/m(2) and Cisplatin 35 mg/m(2) were added into 0.9% NaCl solution 2 000 ml, the infusion velocity was 35-45 ml/min, infusion time was 45-60 minutes, the temperature was controlled to 41°C). A comprehensive evaluation was taken after the fourth course of treatment before operation. Further surgical therapy was performed according to the assessment result.. Sixty-four patients received IHPC combined with systemic chemotherapy. Thirty-two patients(50.0%) had partial response, 18(28.1%) stable disease, and 14(21.9%) progressive disease after chemotherapy. No severe complications or death occurred during the neoadjuvant chemotherapy. Thirty-two patients(50.0%) received radical resection, 10(15.6%) palliative operation, and another 22 patients(37.4%) didn't comply with inclusion criteria of operation. Patients receiving operation had a median survival time of 678 days, which was significantly longer than patients without operation, with a median survival time of 251(χ(2)=23.34, P=0.02).. IHPC combined with systemic chemotherapy is an effective therapeutic method for gastric cancer patients with peritoneal carcinomatosis in terms of reducing preoperative tumor load and achieving radical resection.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Chemotherapy, Cancer, Regional Perfusion; Cisplatin; Combined Modality Therapy; Digestive System Surgical Procedures; Fluorouracil; Humans; Hyperthermia, Induced; Laparoscopy; Leucovorin; Neoadjuvant Therapy; Organoplatinum Compounds; Peritoneal Neoplasms; Peritoneum; Stomach Neoplasms; Treatment Outcome

Despite the positive survival results of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC), criticisms have been put forward regarding the safety of this treatment as a result of a high morbidity rate. Muscle depletion (sarcopenia) is associated with the occurrence of postoperative complications. The purpose of this study was to determine the association between sarcopenia and postoperative morbidity after CRS-HIPEC for peritoneal carcinomatosis from colorectal cancer by distinguishing the complications linked to CRS itself and those associated with chemotherapy (HIPEC) toxicities.. Data concerning 97 consecutive patients who had undergone CRS-HIPEC were recorded. We analyzed the events occurring within 30 days after surgery that were prospectively recorded in a database. Sarcopenia was assessed using the L3 muscle index on computed tomography performed during the 2 months preceding surgery.. The sarcopenic patients experienced significantly more chemotherapy toxicities (57 vs. 26 %; p = 0.004) and especially neutropenia (36 vs. 17 %; p = 0.04) than their nonsarcopenic counterparts. There was no difference in complications linked to the CRS procedure between sarcopenic and nonsarcopenic patients. In the multivariate analysis, sarcopenia was the only parameter independently associated with the risk of chemotherapy toxicity (odds ratio 3.97; 95 % confidence interval 1.52-10.39; p = 0.005).. Despite the local administration of chemotherapy, systemic toxicity was observed in sarcopenic patients after CRS-HIPEC. This relationship favors new treatment strategies with white blood cell growth factors or chemotherapy dosing based on muscle value.

Topics: Administration, Intravenous; Adult; Antineoplastic Combined Chemotherapy Protocols; Body Composition; Camptothecin; Colorectal Neoplasms; Cytoreduction Surgical Procedures; Female; Fluorouracil; Humans; Hyperthermia, Induced; Infusions, Parenteral; Irinotecan; Leucovorin; Male; Middle Aged; Neutropenia; Operative Time; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms; Postoperative Complications; Sarcopenia

Although Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) confers health benefits in peritoneal carcinomatosis (PC) treatment, it is associated with significant postoperative morbidity and mortality rate with increased length of hospital stay. The goal of this study is to determine whether a new comprehensive physiotherapy program including epidural loco-regional analgesia can improve the quality of care and patients recovery.. Between 2009 and 2013, 124 patients with PC were operated for CRS and HIPEC procedures. These patients were analyzed and divided in 2 groups by means of time. No Physio group included patients operated from 2009 to 2011 (n = 57) having a thoracic patient controlled epidural analgesia (PCEA) but no preoperative physiotherapy program. The Physio group included patients operated from 2012 to 2013 (n = 67) having both a PCEA with a preoperative physiotherapy program.. The mortality rate was 1.6% (n = 2). The median length of stay in the intensive care unit (ICU) was lower in the Physio group, 2 days vs. 0 for No Physio group (p < 0.0001). The first time of mobilization after surgery was shorter in the Physio group (day 3 vs. 2, p = 0.0043). The overall satisfaction in the Physio group was achieved in 93% of patients, helping in decreasing fear of surgery and mobilization in 70% and 84% of cases respectively.. Our study demonstrates that a clear pre-operative information and education by a physiotherapist, associated with a PCEA-pain management significantly benefits the patient's post-operative recovery and reduces the length of stay in the ICU.

Topics: Analgesia, Epidural; Analgesia, Patient-Controlled; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Colorectal Neoplasms; Combined Modality Therapy; Cytoreduction Surgical Procedures; Early Ambulation; Female; Fluorouracil; Humans; Hyperthermia, Induced; Infusions, Parenteral; Intensive Care Units; Length of Stay; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Pain, Postoperative; Peritoneal Neoplasms; Physical Therapy Modalities; Postoperative Care; Postoperative Period; Preoperative Care; Quality of Health Care; Retrospective Studies

There are diverse protocols to manage patients with recurrent disease after primary cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis. We describe a case of metachronous liver metastasis after CRS and HIPEC for colorectal cancer, successfully treated with a selective metastectomy and partial graft of the inferior vena cava. A 35-year-old female presented with a large tumour in the cecum and consequent colonic stenosis. After an emergency right colectomy, the patient received adjuvant chemotherapy. One year later she was diagnosed with peritoneal carcinomatosis, and it was decided to carry out a CRS/HIPEC. After 2 years of total remission, an isolated metachronous liver metastasis was detected by magnetic resonance imaging surveillance. The patient underwent a third procedure including a caudate lobe and partial inferior vena cava resection with a prosthetic graft interposition, achieving an R0 situation. The postoperative course was uneventful and the patient was discharged on postoperative day 17 after the liver resection. At 18-mo follow-up after the liver resection the patient remained free of recurrence. In selected patients, the option of re-operation due to recurrent disease should be discussed. Even liver resection of a metachronous metastasis and an extended vascular resection are acceptable after CRS/HIPEC and can be considered as a potential treatment option to remove all macroscopic lesions.

Topics: Adenocarcinoma; Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cecal Neoplasms; Chemotherapy, Adjuvant; Colectomy; Colorectal Neoplasms; Cytoreduction Surgical Procedures; Female; Fluorouracil; Hepatectomy; Humans; Hyperthermia, Induced; Infusions, Parenteral; Leucovorin; Liver Neoplasms; Magnetic Resonance Imaging; Metastasectomy; Organoplatinum Compounds; Peritoneal Neoplasms; Vena Cava, Inferior

Currently, cytoreductive surgery and hyperthermic intraperitoneal chemotherapy are accepted treatments for surgically resectable appendiceal epithelial neoplasms. However, for nonsurgical candidates, systemic treatment may be considered. The purpose of this analysis was to determine the benefit of biologic therapy (anti-vascular endothelial growth factor and anti-epidermal growth factor receptor) in addition to systemic chemotherapy in this select patient population.. The MD Anderson Cancer Center tumor registry was retrospectively reviewed for systemic treatment-naive appendiceal epithelial neoplasm patients registered between January 2000 to July 2007 for prior cytoreductive surgery and hyperthermic intraperitoneal chemotherapy status, histologic grade, signet ring pathology, systemic chemotherapy, biologic therapy, tumor markers (carcinoembryonic antigen, carbohydrate antigen [CA] 125, and/or CA19-9), progression-free survival (PFS), overall survival (OS), and disease control rate. Kaplan-Meier method, log-rank, and Cox proportional hazard regression models were used for statistical analysis.. A total of 353 patients were identified; 130 patients met the inclusion criteria. Fifty-nine patients received biologic therapy. The use of the anti-vascular endothelial growth factor (VEGF) agent bevacizumab improved both OS (42 months vs. 76 months, hazard ratio 0.49 [95 % confidence interval 0.25-0.94] P = 0.03) and PFS (4 months vs. 9 months, hazard ratio 0.69 [95 % confidence interval 0.47-0.995], P = 0.047) for all histologic subtypes. Moderately differentiated tumors had an improved PFS relative to well-differentiated tumors, 9 months versus 3 months (P = 0.05).. Bevacizumab in combination with chemotherapy appears to play a role in surgically unresectable appendiceal epithelial neoplasm patients, with an improvement in PFS and OS. Anti-VEGF agents should be strongly considered in the management of patients with higher-grade appendiceal epithelial neoplasms who are suboptimal candidates for surgical resection.

Topics: Adenocarcinoma, Mucinous; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Appendiceal Neoplasms; Bevacizumab; CA-19-9 Antigen; Camptothecin; Capecitabine; Carcinoembryonic Antigen; Carcinoma, Signet Ring Cell; Cetuximab; Cisplatin; Cytoreduction Surgical Procedures; Disease-Free Survival; ErbB Receptors; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Neoplasm Grading; Organoplatinum Compounds; Peritoneal Neoplasms; Pseudomyxoma Peritonei; Retrospective Studies; Survival Rate; Tumor Burden; Vascular Endothelial Growth Factor A

The role of SC before CRS/HIPEC for patients with PMCA is unclear. This study explores the effect of SC prior to CRS/HIPEC on overall survival (OS) in patients with PMCA.. 72 patients with recently diagnosed PMCA who underwent CRS/HIPEC were identified from a prospective database. Thirty patients had SC before CRS/HIPEC (Group 1) and 42 did not (Group 2). Patients who were referred to our center after multiple lines of SC were excluded from this analysis. OS was estimated.. Median follow-up was 3.2 years. Groups were similar regarding lymph node positivity, postoperative SC and rate of complete cytoreduction. Twenty-four (80%) patients in Group 1 and 21 (50%) in Group 2 had high grade histology (HG) (p = 0.01). OS from CRS/HIPEC at 1, 2, and 3 years was 93, 68, 51% in Group 1 and 82, 64, 60% in Group 2, respectively (p = 0.74). Among HG patients 3-year survival was 36% in the SC group vs. 35% in the group without SC (p = 0.67). The 3-year OS for patients with low grade (LG) tumors was 100% in the SC group vs. 79% in the group with no prior SC (p = 0.26). Among patients with signet ring cell (SRC) histology, 1, 2 and 3-year survival was 94, 67 and 22% in the SC group vs. 43, 14, 14% in the group with no SC, respectively (p = 0.028). There were only 6 patients with LG PMCA who received prior SC.. Preoperative SC could improve the prognosis of patients with high-grade PMCA with SRC histology.

Topics: Adenocarcinoma, Mucinous; Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Appendiceal Neoplasms; Bevacizumab; Camptothecin; Capecitabine; Carcinoid Tumor; Carcinoma, Signet Ring Cell; Cytoreduction Surgical Procedures; Deoxycytidine; Female; Fluorouracil; Humans; Hyperthermia, Induced; Infusions, Parenteral; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms; Peritoneum; Prospective Studies; Retrospective Studies

We report a case of aggressive resection of synchronous and asynchronous peritoneal dissemination of colon cancer, including metastasis to the inguinal hernia sac. A 68-year-old man who was examined for anemia was diagnosed with ascending colon cancer. He underwent right hemicolectomy and resection of the disseminated tumors at the omentum and peritoneum near the Treitz ligament (moderately differentiated tubular adenocarcinoma, pT4a [SE] N0M1P2H0, stageⅣ). After 1 year 6 months, he was readmitted for intestinal obstruction due to the recurrence of peritoneal dissemination, and underwent partial resection of the ileum, liver, and right kidney. In the CT scan examination before surgery, right inguinal hernia and tumor were identified, and hernioplasty with resection of the inguinal tumor was subsequently performed after intestinal obstruction resolution. All tumors were identified as peritoneal dissemination of the colon cancer tumors by pathological examination. After surgery, he was treated with mFOLFOX6 for 6 months and survived without signs of recurrences despite the absence of treatment. Even in cases of peritoneal recurrence of colon cancer, aggressive resection may improve the prognosis in some cases.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Colectomy; Colonic Neoplasms; Fluorouracil; Hernia, Inguinal; Humans; Leucovorin; Male; Organoplatinum Compounds; Peritoneal Neoplasms; Recurrence

Systemic chemotherapy based on 5-fluorouracil (5-FU) is a standard treatment for unresectable or recurrent colorectal cancer. Although hyperammonemia is known as one of the adverse side effects of 5-FU, a disturbance of consciousness caused by hyperammonemia is not a usual finding. We encountered a case of 5-FU-related consciousness disturbance with respiratory depression. A woman in her sixties was diagnosed with metastatic cecum cancer, involving peritoneal dissemination and hydronephrosis due to retroperitoneal invasion. After resection of the primary lesion, systemic chemotherapy, including capecitabine, irinotecan, bevacizumab and cetuximab, was administered for the metastatic lesions. As a third-line of treatment, the mFOLFOX6 plus bevacizumab regimen was administered. On the second day of the first course, the patient complained of nausea and vomiting. On third day, her consciousness level was deteriorating. The level of ammonia in the blood was abnormally high. Therefore, we diagnosed consciousness disturbance caused by hyperammonemia resulting from high-dose 5-FU infusion. The symptom improved immediately after mechanical ventilation and intravenous infusion. Renal dysfunction is considered a risk factor for hyperammonemia caused by 5-FU, and it is necessary to pay particular attention in patients with renal dysfunction who receive chemotherapy with 5-FU.

Topics: Antineoplastic Combined Chemotherapy Protocols; Appendiceal Neoplasms; Colectomy; Consciousness; Female; Fluorouracil; Humans; Hyperammonemia; Leucovorin; Nausea; Organoplatinum Compounds; Peritoneal Neoplasms

A microscopically irradical (R1) resection is a well-known adverse prognostic factor after gastric cancer surgery. However, the prognostic significance of an R1 resection in gastric cancer patients who are treated with chemoradiotherapy (CRT) after the operation has been poorly studied. Therefore, the aim of this study was to evaluate the effect of an R1 resection on (recurrence-free) survival in gastric cancer patients who were treated with CRT after surgery.. Gastric cancer patients who had undergone a resection with curative intent followed by adjuvant CRT at our institute between 2001 and 2011 were included. CRT consisted of radiotherapy (45 Gy/25 fractions) combined with concurrent capecitabine (with or without cisplatin) or 5-fluorouracil/leucovorin.. A consecutive series of 110 patients was studied, including 80 (73 %) patients who had undergone an R0 resection and 30 (27 %) patients with an R1 resection. Pathologic T-classification (p = 0.26), N-classification (p = 0.77), and histologic subtype according to Laurén (p = 0.071) were not significantly different between these groups. Three-year recurrence-free survival (45 vs. 35 %, p = 0.34) and overall survival (47 vs. 48 %, p = 0.58) did not significantly differ between patients who had undergone an R0 or R1 resection. In a multivariate analysis, pathologic T-classification and N-classification were independent prognostic factors for survival.. A R1 resection was not an adverse prognostic factor in gastric cancer patients who had undergone CRT after the operation.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemoradiotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Deoxycytidine; Female; Fluorouracil; Follow-Up Studies; Gastrectomy; Humans; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Peritoneal Neoplasms; Prognosis; Retrospective Studies; Stomach Neoplasms; Survival Rate

Patients with stage IV colorectal cancer and peritoneal carcinomatosis are increasingly treated with curative intent and perioperative systemic chemotherapy combined with targeted therapy. The aim of this study was to analyze the potential impact of bevacizumab on early morbidity after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal carcinomatosis of colorectal origin.. From 2004 to 2010, in three referral centers, 182 patients with colorectal carcinomatosis were treated with complete cytoreduction followed by HIPEC after either preoperative systemic chemotherapy alone or in combination with bevacizumab. Because there was no control on treatment allocation, propensity score methods were used to control for this bias.. The median time from discontinuation of bevacizumab to HIPEC was 7 weeks (range 6-10 weeks). Major morbidity was greater in the bevacizumab group (34 vs. 19 %, p = 0.020). Nine patients died postoperatively, 5 (6.2 %) in the bevacizumab group (n = 80) and 4 (3.9 %) in the group treated with chemotherapy alone (n = 102) (p = 0.130). The rate of digestive fistulas was greater in the bevacizumab group, although not statistically significant (18 vs. 10 %, p = 0.300). The effect of bevacizumab on major morbidity (including death) was found to be statistically significant (odds ratio 2.28, 95 % confidence interval 1.05-4.95) (p = 0.04).. Administration of bevacizumab before surgery with complete cytoreduction followed by HIPEC for colorectal carcinomatosis is associated with twofold increased morbidity. The oncologic benefit of bevacizumab before HIPEC remains to be evaluated.

Topics: Abdominal Abscess; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Carcinoma; Chemotherapy, Adjuvant; Colorectal Neoplasms; Cytoreduction Surgical Procedures; Digestive System Fistula; Female; Fluorouracil; Hematoma; Humans; Hyperthermia, Induced; Length of Stay; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Peritoneal Neoplasms; Wound Healing

The standard treatment of peritoneal pseudomyxoma is based on cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC). The establishment of newer systemic treatments is an unmet clinical need for unresectable or relapsed peritoneal pseudomyxoma. The aim of our study was to assess the activity of chemotherapy with 5-fluorouracil and oxaliplatin (FOLFOX-4 regimen) in terms of response rate in this subset of patients.. Patients were included in a single-center, observational study and treated with FOLFOX-4 administered every 2 weeks for up to 12 cycles or until progressive disease or unacceptable toxicity.. Twenty consecutive patients were reviewed from July 2011 to September 2013. Only partial responses were observed, with an objective response rate of 20%. Median progression-free survival and overall survival were 8 months and 26 months, respectively. Two patients were able to undergo laparotomy with complete cytoreduction and HIPEC in one case. Safety data for FOLFOX-4 were consistent with the literature. By means of a mutant enriched polymerase chain reaction, KRAS mutation was found in 16 of 19 cases (84%), and MGMT promoter methylation was found in 8 (42%, all KRAS mutant).. FOLFOX-4 chemotherapy is tolerable and active in patients with peritoneal pseudomyxoma when disease is deemed unresectable or relapsed after peritonectomy and HIPEC. The identification of predictive biomarkers, such as KRAS for resistance to anti-epidermal growth factor receptor monoclonal antibodies and MGMT for response to temozolomide, is a priority for the development of evidence-based treatment strategies for peritoneal pseudomyxoma.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; DNA Methylation; DNA Modification Methylases; DNA Repair Enzymes; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Peritoneal Neoplasms; Proto-Oncogene Proteins; Proto-Oncogene Proteins p21(ras); Pseudomyxoma Peritonei; ras Proteins; Treatment Outcome; Tumor Suppressor Proteins

Inoperable pancreatic ductal adenocarcinoma is known to have an extremely poor prognosis. Although rare, there are some patients who have unexpected long-term survival, but the reason is not yet clear.. A total of 482 inoperable pancreatic ductal adenocarcinoma of 1602 patients diagnosed at Severance Hospital between 2002 and 2009 were evaluated, who were selected statistically with a retrospective cohort study. They were divided into locally advanced pancreatic cancer (LAPC) and metastatic pancreatic cancer (MPC). Short-term survivors (SS group) were defined as patients who survived less than 9 months with LAPC and 6 months with MPC. Patients who survived 3 times longer than the SS group were classified as long-term survivors (LS group). Predictive factors of long-survival were identified by comparing the 2 groups, and effects of these factors on survival were investigated statistically.. In multivariate analysis, better performance status and lower CA19-9 were related to overall survival in LAPC. In MPC, younger age, better performance status, peritoneal metastasis, higher serum albumin, lower CA19-9, and CA19-9 variation were related to overall survival.. These parameters related to long-term survivors of advanced pancreatic cancer can be useful for the expectation of survival. In the near future, conjunction of these clinical factors and novel molecular biologic characteristics of individual patients can be used for the personalized therapy.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Camptothecin; Carcinoma, Pancreatic Ductal; Chemoradiotherapy; Combined Modality Therapy; Deoxycytidine; Disease-Free Survival; Erlotinib Hydrochloride; Female; Fluorouracil; Gemcitabine; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Pancreatic Neoplasms; Peritoneal Neoplasms; Prognosis; Proportional Hazards Models; Quinazolines; Republic of Korea; Retrospective Studies; Survivors; Treatment Outcome

A case is presented of a 36-year-old male with primary sclerosing cholangitis-associated inflammatory bowel disease (PSC-IBD) and two synchronous stage 1 adenocarcinomata of the colon, who was initially treated with a subtotal colectomy with ileostomy. One year later, the patient presented with extensive intra-abdominal lymphadenopathy and peritoneal carcinomatosis, as well as a markedly elevated serum level of alpha-fetoprotein (AFP). Fine needle aspiration biopsy of a porta hepatis lymph node revealed a metastatic hepatoid adenocarcinoma. Subsequent review of the previous colectomy specimen showed that one of the previously identified adenocarcinomata had features suggestive of a hepatoid colonic adenocarcinoma. The patient was subsequently treated with a cytotoxic regimen of FOLFOX (oxaliplatin, leucovorin, 5-fluorouracil) and bevacizumab, with stable results being achieved after six months. This case presents the first known report of PSC-IBD associated with synchronous typical and hepatoid adenocarcinomata of the colon and highlights the importance of considering hepatoid adenocarcinoma as a differential diagnosis in patients with an increasing serum AFP level.

Topics: Adenocarcinoma; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Biopsy; Cholangitis, Sclerosing; Colectomy; Colitis, Ulcerative; Colonic Neoplasms; Fluorouracil; Humans; Ileostomy; Jejunostomy; Leucovorin; Male; Middle Aged; Neoplasm Staging; Neoplasms, Multiple Primary; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms; Risk Factors; Time Factors; Treatment Outcome

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 evaluated the efficacy and safety of bevacizumab for metastatic colorectal cancer patients.. All unresectable metastatic colorectal cancer patients who began receiving bevacizumab at participating facilities from 2006 to 2011 were retrospectively analyze to determine the safety and efficacy. The primary end points were Progression Free Survival (PFS) and Overall Survival (OS). The secondary end points were adverse events.. A total of 101 patients were enrolled in the study. The primary tumor site was the colon in 53 patients and the rectum in 48 patients. The most common metastatic sites were the liver (63.4%), lung (31%), and peritoneum (10%). In first-line therapy, 76 (75.2%) patients received the FOLFOX regimen. Among these patients, 33 (43.4%) patients received FOLFOX alone, and 43 (56.6%) received FOLFOX plus bevacizumab. The addition of bevacizumab to first-line chemotherapy was associated with increases in median PFS (12.5 vs. 6.0 months; P = .00001) and median OS (24.0 vs. 16.0 months; P = 0.0221). The risks of adverse events were not significantly increased with the addition of bevacizumab.. The addition of bevacizumab to first-line therapy in CRC patients provided clinically significant patient benefit, including statistically significant improvement in OS and a favorable tolerability profile.

Topics: Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colorectal Neoplasms; Disease Progression; Disease-Free Survival; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms; Retrospective Studies; Time Factors; Treatment Outcome

The aim was to evaluate the feasibility and the effectiveness of neoadjuvant systemic chemotherapy using FLOT - protocol followed by cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC) followed by systemic chemotherapyand in patients with peritoneal carciriomatosis (PC) from gastric cancer.. Twenty six (median age 53 years, range 39 - 71) were scheduled for three cycles of neoadjuvant systemic chemotherapy using bi-weekly FLOT - protocol followed by CRS + HIPEC. Thereafter 3 additional cycles of FLOT were given. During HIPEC in Colliseum technique Oxaliplatin was given in a dosage of 200 mg/m2 and Docetaxel in a dosage of 80 mg/m2.. All patients underwent cytoreductive surgery plus HIPEC. Peritoneal Cancer index was > 15 in 3 cases only. Complete resection could be carried out in all cases (CC-O 18, CC-18). Postoperative complication rate was 23% with no mortality within 30 days. Anastomotic leakage rate was 3.2%. Overall survival was 19.0 months with a 2-year survival rate 38%. Regression analysis demonstrated a Peritoneal Cancer Index PCI > 12 as negative factor for survival.. Neoadju- vant chemotherapy using FLOT - protocol followed by CRS + HIPEC seems to be associated with prolonged OS in patients with peritoneal carcinomatosis from gastric cancer. This treatment is not recommended for patients with extensive peritoneal involvement and PCI > 12.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cytoreduction Surgical Procedures; Docetaxel; Drug Administration Schedule; Female; Fluorouracil; Humans; Hypothermia, Induced; Infusions, Parenteral; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms; Retrospective Studies; Stomach Neoplasms; Taxoids; Time Factors; Treatment Outcome

High-grade appendiceal adenocarcinoma is a rare malignancy with propensity for peritoneal metastases (PM). The impact of neoadjuvant chemotherapy on operative cytoreduction (CRS) and intraperitoneal chemotherapy (HIPEC) and patient survival was reviewed.. A total of 45 patients with PM from high-grade appendiceal adenocarcinoma were identified from a prospective database. All patients had laparotomy with intent to undergo CRS and HIPEC. Operative parameters, complications, and survival outcomes were analyzed.. Of the 45 patients (male: 27, female: 18; median age: 55 years), 26 received neoadjuvant chemotherapy ± bevacizumab. Of the 26, 15 (58 %) had a response based on improvement in imaging, biomarkers, or both and 9 (34 %) had stable disease. The median peritoneal cancer index (PCI) was 27. Also, 30 (67 %) had a completeness of cytoreduction score (CCR) of ≤1 and 37 (82 %) received HIPEC. There were no differences in PCI, CCR score, operative blood loss, or major organ resection between those who received or did not receive neoadjuvant chemotherapy. Operative time was significantly shorter in those who did not receive neoadjuvant chemotherapy. Major complications and length of hospital stay were similar between the groups. The median actuarial overall survival calculated from the date of initial therapeutic intervention was not different in those treated with or without neoadjuvant therapy.. Neoadjuvant chemotherapy has marked clinical activity in patients with PM from high-grade appendiceal adenocarcinoma and does not adversely affect operative outcomes. These data support conducting a prospective clinical trial to define the role of neoadjuvant chemotherapy in this clinical setting.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Appendectomy; Appendiceal Neoplasms; Bevacizumab; Chemotherapy, Adjuvant; Chemotherapy, Cancer, Regional Perfusion; Combined Modality Therapy; Female; Fluorouracil; Follow-Up Studies; Humans; Hyperthermia, Induced; Leucovorin; Male; Middle Aged; Mitomycin; Neoadjuvant Therapy; Neoplasm Grading; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms; Prognosis; Prospective Studies; Retrospective Studies; Survival Rate

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) achieves disease control within the peritoneum but recurrences occur. This study examines the outcomes of iterative CRS (iCRS) HIPEC for treatment of recurrent peritoneal metastases.. Patients who underwent iCRS in a single tertiary referral center were identified from a prospective database. Safety analysis was performed and clinicopathological variables were analyzed to assess factors predictive of major morbidity and survival.. The demographics of patients who underwent primary cytoreductive surgery (pCRS) (n = 466) and iCRS (n = 79) were balanced between groups. pCRS was shown to require more blood transfusion (P = 0.019) and albumin use (P = 0.013). The mortality and major complication rates were comparable (1.2% vs. 0%; P = 0.600, and 42% vs. 41%; P = 0.806). Residual pneumothorax occurred more frequently after pCRS (12% vs. 4%; P = 0.030). Factors associated with major complications after iCRS include use of HIPEC (P = 0.042) and length of hospital stay (P = 0.024). The overall median survival was 48 months and 5-year survival was 34%. By cancer type, the 3-year survival was 0%, 74%, 80%, and 72% for colorectal, appendiceal pseudomyxoma, peritoneal mesothelioma, and appendix cancer, respectively. Independent predictors of survival include age (P = 0.049), interval between pCRS and iCRS (P = 0.008), small bowel resection (P < 0.001), and use of HIPEC (P = 0.005).. Iterative CRS achieved further peritoneal disease control without adverse effects on morbidity. Patients with appendiceal tumors and peritoneal mesothelioma appear to benefit most after iCRS. Intraoperative HIPEC remains important in the repetoire of managing these patients.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Doxorubicin; Female; Fluorouracil; Follow-Up Studies; Humans; Hyperthermia, Induced; Leucovorin; Male; Middle Aged; Mitomycin; Neoplasm Recurrence, Local; Organoplatinum Compounds; Oxaliplatin; Perfusion; Peritoneal Neoplasms; Peritoneum; Postoperative Complications; Reoperation; Retrospective Studies; Survival Analysis; Treatment Outcome

We present the clinical observation of combined treatment of a patient with metastatic gastric cancer. The patient underwent combined chemotherapy for initially inoperable gastric cancer with metastases to the liver, paragastric lymph nodes, and peritoneal carcinomatosis with complete regression of distant metastases, which allowed radical surgery. The patient is currently under regular team observation without signs of disease. His present survival is 44 months.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Fluorouracil; Gastrectomy; Humans; Induction Chemotherapy; Leucovorin; Liver Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Peritoneal Neoplasms; Stomach Neoplasms; Taxoids; Treatment Outcome

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

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) provide a promising therapeutic option for selected patients with peritoneal carcinomatosis. The use of intraperitoneal oxaliplatin seems to further improve the efficacy of the combined treatment concept. Nevertheless, additional toxicity might be expected.. Between 03/2004 and 08/2010 307 patients underwent CRS and HIPEC at the University Medical Center Regensburg. Forty of these patients received oxaliplatin-based HIPEC. A matched-pair analysis was performed to compare IP oxaliplatin to our former standard HIPEC protocol with mitomycin C (MMC) and doxorubicin.. The mean operating time in the OX and the MMC group was 315 and 313 min, respectively. Median hospital stay was 15.5 days in the OX group and 17 days in the MMC group. The grade 3/4 morbidity rate according to CTCAEv3.0 was 42.5% versus 37.5% (P = 0.648). Perioperative mortality was 2.5% versus 0%.. Our data suggest that the use of IP oxaliplatin in the context of CRS and HIPEC does not significantly increase perioperative morbidity and/or mortality rates. Nevertheless, randomized controlled trials are required to determine the optimal intraperitoneal chemotherapeutic regimen regarding toxicity, postoperative complications, and oncological outcome.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Chemotherapy, Cancer, Regional Perfusion; Colorectal Neoplasms; Doxorubicin; Female; Fluorouracil; Humans; Hyperthermia, Induced; Infusions, Parenteral; Length of Stay; Leucovorin; Male; Matched-Pair Analysis; Middle Aged; Mitomycin; Operative Time; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms; Peritoneum; Postoperative Complications; Retrospective Studies; Treatment Outcome

Five prognostic factors had been previously identified in patients with metastatic colorectal cancer (MCRC) who received irinotecan-based second-line chemotherapy. Patients were classified into three prognostic groups based on significant differences in median overall survival (OS). This study is conducted to validate this classification in an external validation cohort.. This retrospective study included 193 patients of an external validation cohort who received irinotecan-based second-line chemotherapy after first-line oxaliplatin-based chemotherapy, with or without bevacizumab at three institutions.. Three of the five predefined factors (poorly differentiated adenocarcinoma, LDH ≥400 IU/L, progression-free survival of first-line therapy <6 months) remained highly significant in the validation cohort, although two (performance status 2 and peritoneal metastasis) were associated with borderline significance. The distribution of the three prognostic groups (low risk = no factors, intermediate risk = 1 factor, high risk = 2 or more factors) was low risk (n = 68; 35 %), intermediate risk (n = 80; 41 %), and high risk (n = 45; 23 %). The median OS of each group were 19.8, 11.0, and 7.9 months, respectively, with significant differences between groups, as found in the previous cohort.. The previous prognostic classification of patients with MCRC who received irinotecan-based second-line chemotherapy was validated in another independent cohort. Validation in prospective studies is warranted.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Cohort Studies; Colorectal Neoplasms; Female; Fluorouracil; Follow-Up Studies; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms; Prognosis; Survival Rate

According to the 7th edition of the TNM staging system, stage IV metastatic colorectal cancer (CRC) at the time of initial diagnosis is sub-classified into stage IVA or IVB disease. Peritoneal carcinomatosis (PC), considered to have a dismal prognosis, is exclusively sub-classified into stage IVB, even though other metastases to a sole organ are sub-classified into stage IVA, which is considered to be associated with better survival. This retrospective study was undertaken to investigate the overall survival in metastatic CRC patients, focusing on PC patients.. We reviewed data on patients with metastatic CRC at initial diagnosis surgically treated between January 2006 and June 2011. A survival analysis was performed paying special attention to PC and sub-classifying patients with PC into three categories according to metastatic sites.. There were 69 stage IVA patients (IVA group) and 83 stage IVB. Among stage IVB patients, 20 had isolated PC (PC-I group), 28 had PC with one or more other sites of metastasis (PC-II group), and 35 had at least 2 metastatic without peritoneal involvement (NPC group). Of 152 stage IV patients, 132 (87 %) underwent resection of the primary tumor and 19 (12 %) underwent radical resection of metastatic disease with microscopic free margins (R0 resection) including 5/20 (25 %) patients in the PC1 group. A total of 139 patients received oxaliplatin-based chemotherapy in a palliative (n = 125), neoadjuvant (n = 3), or adjuvant setting after R0 resection (n = 11). Compared with 36.6 months in the PC-I group, median survival was 32.5 months (P = 0.48) in the IVA group, 14.7 months (P = 0.07) in the PC-II group, and 12.9 months (P < 0.01) in the NPC group.. The sub-classification of isolated PC into stage IVA instead of IVB might be more appropriate in the era of modern chemotherapy. Further investigation is warranted.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Carcinoma; Chemotherapy, Adjuvant; Colorectal Neoplasms; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Palliative Care; Peritoneal Neoplasms; Prognosis; Retrospective Studies

Although cytoreductive surgery and intraperitoneal chemotherapy have been advocated as standard treatment for appendiceal neoplasms with isolated peritoneal metastasis, the optimal method of chemotherapy administration has not been established. At our institution, patients undergoing complete cytoreduction in this setting typically receive multiple cycles of early postoperative intraperitoneal chemotherapy.. The aim of this study was to describe patients with appendiceal neoplasms and peritoneal dissemination treated with complete cytoreductive surgery and early postoperative intraperitoneal chemotherapy and to document associated time to progression and morbidity.. This is a retrospective study at a single specialty institution. Hospital and departmental databases were searched for patients presenting with primary appendiceal neoplasms undergoing cytoreductive surgery, placement of intraperitoneal port, and subsequent intraperitoneal chemotherapy from June 1995 to September 2009.. This study was conducted at Memorial Sloan-Kettering Cancer Center.. We identified 50 patients (30 female), median age 48 (range, 26-66) who met the criteria.. Cytoreductive surgery, placement intraperitoneal port, and intraperitoneal chemotherapy were performed.. All patients underwent intraperitoneal catheter placement after complete cytoreductive surgery, followed by a median of 4 cycles (range, 1-9) intraperitoneal 5-fluoro-2'-deoxyuridine (1000 mg/m daily for 3 days) plus leucovorin (240 mg/m). The median hospital length of stay was 9 days (maximum, 29). Thirty-four percent of the patients experienced complications; 12% experienced major complications (3 abdominal abscesses, 1 deep vein thrombosis, 1 abdominal hemorrhage, and 1 intraperitoneal port malfunction). There were no 30-day mortalities. Five-year recurrence-free interval was observed in 43%. Among 23 patients with recurrence, 18 had a recurrence only within the peritoneum. The median overall survival was 9.8 years.. This is a retrospective study. Many patients had surgery first at other institutions; therefore, pathologic examination of resected material was not possible in every case. Other factors possibly impacting time to recurrence (ie, preoperative chemotherapy, duration between onset of disease and presentation to our institution) varied among patients and were not controlled for. In the absence of a control arm undergoing complete cytoreduction without early postoperative intraperitoneal chemotherapy, we did not ascertain whether intraperitoneal chemotherapy confers additional benefit.. Cytoreductive surgery plus multiple cycles of early postoperative intraperitoneal chemotherapy is safe, achieving survival results similar to published outcomes of other protocols (including hyperthermic intraperitoneal chemotherapy). Prospective trials are warranted to compare various methods of intraperitoneal chemotherapy in this setting.

Topics: Adenocarcinoma, Mucinous; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Appendiceal Neoplasms; Combined Modality Therapy; Disease Progression; Drug Administration Schedule; Female; Floxuridine; Humans; Infusions, Parenteral; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Peritoneal Neoplasms; Retrospective Studies; Survival Analysis; Treatment Outcome

A 16-year-old girl presented to our unit with crampy abdominal pain, change in bowel habit, a subjective impression of weight loss and a single episode of haematochezia. She was found to have a rectosigmoid adenocarcinoma and proceeded to laparoscopic anterior resection, whereupon peritoneal metastases were discovered. She received chemotherapy and is alive and well ten month later with no radiological evidence of disease. Colorectal carcinoma is rare in the paediatric population but is increasing in incidence. Early diagnosis is critical to enable optimal outcomes.

Topics: Adolescent; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Carcinoma, Signet Ring Cell; Colorectal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Organoplatinum Compounds; Peritoneal Neoplasms

Although systemic therapies have shown to result in survival benefit in patients with metastatic colorectal cancer (mCRC), outcomes in patients with peritoneal carcinomatosis (PC) are poor. No data are available on outcomes of current chemotherapy schedules plus targeted agents in mCRC patients with PC.. Previously untreated mCRC patients treated with chemotherapy in the CAIRO study and with chemotherapy and targeted therapy in the CAIRO2 study were included and retrospectively analysed according to presence or absence of PC at randomisation. Patient demographics, primary tumour characteristics, progression-free survival (PFS), overall survival (OS), and occurrence of toxicity were evaluated.. Thirty-four patients with PC were identified in the CAIRO study and 47 patients in the CAIRO2 study. Median OS was decreased for patients with PC compared with patients without PC (CAIRO: 10.4 versus 17.3 months, respectively (p ≤ 0.001); CAIRO2: 15.2 versus 20.7 months, respectively (p < 0.001)). Median number of treatment cycles did not differ between patients with or without PC in both studies. Occurrence of major toxicity was more frequent in patients with PC treated with sequential chemotherapy in the CAIRO study as compared to patients without PC. This was not reflected in reasons to discontinue treatment. In the CAIRO2 study, no differences in major toxicity were observed.. Our data demonstrate decreased efficacy of current standard chemotherapy with and without targeted agents in mCRC patients with PC. This suggests that the poor outcome cannot be explained by undertreatment or increased susceptibility to toxicity, but rather by relative resistance to treatment.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Chemotherapy, Adjuvant; Colorectal Neoplasms; Disease-Free Survival; Drug Administration Schedule; Drug Resistance, Neoplasm; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Molecular Targeted Therapy; Neoplasm Staging; Peritoneal Neoplasms; Randomized Controlled Trials as Topic; Retrospective Studies; Treatment Failure; Treatment Outcome

A 50-year-old woman was diagnosed with ascending colon cancer with bilateral ovarian metastases, carcinomatous peritonitis, and carcinomatous pleurisy. Nine courses of mFOLFOX6 treatment resulted in the disappearance of her ascites and pleural effusion and a marked decrease in her serum CEA and CA19-9 levels. Additionally, the primary tumor and ovarian metastases became smaller. Therefore, a right hemicolectomy with D3 lymph node dissection, total hysterectomy, and bilateral salpingo-oophorectomy were performed. Postoperatively, we changed the chemotherapy from mFOLFOX6 to bevacizumab+FOLFIRI because the patient had an allergic reaction to oxaliplatin, and we suspected lung metastasis. Because the lung metastasis grew after ten courses of bevacizumab+FOLFIRI, we changed to cetuximab+FOLFIRI. Unfortunately, 28 months after her diagnosis, the patient died of carcinomatous pleurisy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Fatal Outcome; Female; Fluorouracil; Humans; Leucovorin; Middle Aged; Neoplasm Grading; Organoplatinum Compounds; Ovarian Neoplasms; Peritoneal Neoplasms

A 63-year-old woman with chief complaints of abdominal distention and vomiting was brought to our hospital in May, 2010. Her radiological examination revealed that she was suffering from perforative peritonitis. The patient underwent emergency open laparotomy. Perioperatively, we made a diagnosis of unresectable transverse colon cancer accompanied with tough peritoneal dissemination, and therefore performed intraperitoneal irrigation drainage, transverse loop colostomy and biopsy of omental dissemination. A pathological examination of omental dissemination demonstrated mucinous adenocarcinoma with the wild-type Kras gene, and the cytology of ascites was negative. FOLFOX4 combined with panitumumab therapy was initiated 1 month after the operation. Seventeen courses of this chemotherapy regimen were performed, although adverse events including grade 3 neutropenia and grade 2 skin symptoms were noted. Consequently, serum CEA levels decreased to 5. 5 ng/mL, although the size of the primary lesion of transverse colon cancer was unchanged on abdominal computed tomography(CT). Chemotherapy has been continued without marked side effects, although 1 year has passed since we started medical treatment for this difficult case. We found that a multidisciplinary approach with a focus on FOLFOX4 therapy combined with panitumumab is useful for patients with highly advanced mucinous adenocarcinoma of the colon that develops into peritoneal dissemination.

Topics: Adenocarcinoma, Mucinous; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Middle Aged; Organoplatinum Compounds; Panitumumab; Peritoneal Neoplasms; Tomography, X-Ray Computed

A38 -year-old man complaining of abdominal pain was diagnosed with small intestinal cancer. Small intestinal endoscopy and PET-CT showed a primary jejunal cancer and five peritoneal metastases. Partial resection of the jejunum with three metastases was performed, but the others were unresectable. After surgery, FOLFOX chemotherapy was adapted. Follow-up pelvic CT showed a remarkable reduction of tumor size during FOLFOX chemotherapy after 4 courses, and follow-up PET-CT showed no tumor intake FDG after 10 courses. We judged him to be a complete response and stopped chemotherapy. After 7 months, the patient's level of tumor markers elevated, and there was recurrence. We resumed FOLFOX, and the chemotherapy for this patient is still being continued.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Jejunal Neoplasms; Leucovorin; Male; Neoplasm Invasiveness; Organoplatinum Compounds; Peritoneal Neoplasms; Recurrence

Mucinous adenocarcinoma (MA) of colorectal cancer seems associated with reduced responsiveness to chemotherapy. The overexpression of markers of resistance to fluorouracil and oxaliplatin has recently been demonstrated. We revised the outcomes of metastatic MA of the colon treated with FOLFOX. From January 2002 to December 2009, we treated 198 patients with metastatic colon cancer, of which 21 (10.6%) had diagnosis of MA and were compared with 42 control patients with non-mucinous adenocarcinoma (NMA). In MA group, three patients [14%; inhibitory concentration 95: ± 7.5%] reached partial response, and in NMA group, two patients obtained complete response and 16 obtained partial response with an overall response rate of 43% (inhibitory concentration 95: ± 7.6%) with a significant statistical difference (P = 0.027). Median progression-free survival for MA group was 4 months with respect to 8 months for NMA (P = 0.0001); regarding overall survival, we registered a median of 8 months with respect to 18 months for MA and NMA (P = 0.001). In multivariate analysis, MA histology, Eastern Cooperative Oncology Group performance status 2, more than two metastatic sites, and peritoneal metastatic involvement resulted in negative independent prognostic factors. Also in our study, MA is connected to poor prognosis and reduced activity of chemotherapy. In the absence of randomised studies, it may be convenient to analyse this subgroup of patients within the large trials carried out on colorectal cancer.

Topics: Activities of Daily Living; Adenocarcinoma, Mucinous; Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Drug Resistance, Neoplasm; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms; Prognosis; Remission Induction; Retrospective Studies; Survival Analysis

Even in the era of new anticancer drugs, an optimal treatment strategy for colorectal cancer associated with liver metastasis and peritoneal carcinomatosis has yet to be established. Here we report the case of a long-term survivor with very advanced colon cancer who underwent repeated resective surgery and chemotherapy. This 69-year-old man underwent a Hartmann's procedure and the resection of peritoneal metastases of cancer of the rectosigmoid, which had infiltrated the retroperitoneum giving rise to multiple liver metastases and peritoneal carcinomatosis. The resection margin was positive for cancer. After 14 courses of a modified FOLFOX6 (mFOLFOX6) regimen, a partial response with no development of new lesions was obtained. Multiple partial hepatectomies were subsequently performed. After the completion of an additional 6 courses of mFOLFOX6, a positron-emission tomography (PET)/computed tomography (CT) examination demonstrated a hot spot in segment 4. This hot deposit disappeared after a further 8 courses of mFOLFOX6. The patient then underwent a left lateral segmentectomy for a newly developed lesion in segment 3, which was detected 2 years and 7 months after the first operation. The patient has remained free from recurrence for 2 years since his last operation.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Organoplatinum Compounds; Peritoneal Neoplasms; Sigmoid Neoplasms; Time Factors

Failure to respond to systemic chemotherapy is considered an exclusion criterion by some institutions for treatment with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). However, it is unknown if these patients benefit from HIPEC treatment. This study aimed to report on outcomes of HIPEC in patients who failed to respond to adjuvant systemic chemotherapy.. Patients were selected from a prospective database containing data on all patients who underwent HIPEC, using the following criteria: (1) Metachronous peritoneal carcinomatosis (PC) from colorectal origin, (2) adjuvant chemotherapy after primary tumor resection, (3) development of PC or local recurrence within 18 months after start of chemotherapy. Treatment and survival data were retrospectively collected.. Twenty-one patients (29% male, mean age 57 years) were included. Median time to recurrence of disease was 9 months (range 2-15) after first chemotherapy administration. Median survival was 28 months (range 3-100). One- and 2-year survival were 71% and 43%, respectively.. Patients who initially failed to respond to systemic adjuvant treatment showed a survival after HIPEC similar to results reported in literature in patients with unknown responsiveness. Failure to respond to previous adjuvant systemic treatment should therefore not be considered an exclusion criterion for HIPEC treatment.

Topics: Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Colorectal Neoplasms; Combined Modality Therapy; Deoxycytidine; Female; Fluorouracil; Follow-Up Studies; Humans; Hyperthermia, Induced; Infusions, Parenteral; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms; Prospective Studies; Retrospective Studies; Survival Rate; Treatment Outcome

Operation results of 81 colorecatal cancer-patients with peritoneal carcinomatosis (PC) treated with peritonectomy plus perioperative chemotherapy are reported. The patients who had the following evidences are considered to be eligible for peritonectomy: 1) No evidence of N3 lymph node involvement, 2) No evidence of hematogenous metastasis, 3) No progressive disease after preoperative chemotherapy, 4) No severe co-morbidities or no poor general condition. Complete cytoreduction resection is aimed for removing all macroscopic tumors by peritonectomy using electrosurgical techniques. The completeness of cytoreduction (CC scores) after peritonectomy is classified into the following 4 criteria: CC-0-no peritoneal seeding was exposed during the complete exploration, CC-1-residual tumor nodules are less than 2.5 mm in diameter, CC-2-nodules are between 2 .5 mm and 25 mm in diameter, CC-3-nodules are greater than 25 mm in diameter, CC-2 and CC-3 are regarded as incomplete cytoreduction. Operation time and blood loss were 237 ± 124 min. (799-90 min) and 1,598 ± 1,411 mL (6,500-20 mL), respectively. Postoperative complications developed in 37( 46%) patients. The patients received CC-0/ -1 resection survived significantly longer than those of CC-2/ -3 group. The patients with PCI ≤ 10 survived significantly longer than those with PCI≥ 11. CC and PCI scores are the independent prognostic factors. The relative risk for death of CC-2/-3 group was 4.6-fold higher than that of CC-0/ -1 group. Accordingly, peritonectomy is indicated for patients with PCI score≤ 10.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma; Colorectal Neoplasms; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Pelvic Exenteration; Peritoneal Neoplasms; Young Adult

A 58-year-old woman, who was undergoing peritoneal dialysis( PD) for chronic kidney disease (CKD) and had been operated by sigmoidectomy for early colonic cancer, was diagnosed as peritoneal recurrence of the colonic cancer. Her treatment for CKD was switched from PD to hemodialysis. She was administered mFOLFOX6 therapy(reducing the dose to 70%). Hemodialysis was performed 1 hour after administration of oxaliplatin on day 1 and repeated two days later after the completion of drug administration. No serious adverse events were observed. After 10 courses of mFOLFOX6, an ovarian metastasis was appeared. We then changed the regimen to FOLFIRI (70% dose)/bevacizumab (BV). Neutropenia (grade 4) was observed after the second treatment. After some rest, 21 courses of FOLFIRI/BV therapy were performed safely by reducing the dose to 60%. We thought that a reduced dose of FOLFIRI/BV therapy appeared to be safe for a patient with chronic kidney disease who is on hemodialysis.

Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colonic Neoplasms; Female; Fluorouracil; Humans; Kidney Failure, Chronic; Leucovorin; Middle Aged; Organoplatinum Compounds; Peritoneal Dialysis; Peritoneal Neoplasms

Small-bowel adenocarcinoma (SBA) is a rare tumor of poor prognosis. Data on the efficacy of chemotherapy for advanced SBA are scarce.. All patients with advanced SBA who received frontline chemotherapy from 1996 to 2008 were eligible for this retrospective multicenter study.. Ninety-three consecutive patients were included. In the entire population, the median progression-free survival (PFS) and overall survival (OS) times were 6.6 and 15.1 months, respectively. Median PFS times among patients treated with LV5FU2 (n = 10), FOLFOX (n = 48), FOLFIRI (n = 19) and LV5FU2-cisplatin (n = 16) were 7.7, 6.9, 6.0 and 4.8 months, respectively, while median OS times were 13.5, 17.8, 10.6 and 9.3 months, respectively. In multivariate analysis, World Health Organization performance status (PS) (P < 0.0001) and elevated serum levels of carcinoembryonic antigen (CEA) (P = 0.02) and carbohydrate antigen 19-9 (CA 19-9) (P = 0.03) were the only variables significantly associated with poor OS. In the subgroup of patients treated with platinum-based chemotherapy, multivariate analysis showed that LV5FU2-cisplatin was associated with poorer PFS (P < 0.0001) and OS (P = 0.02) compared with FOLFOX.. This is the largest study of chemotherapy in advanced SBA. Baseline PS and CEA and CA 19-9 levels were the main prognostic factors. FOLFOX seems to be the most effective platinum-based chemotherapy regimen.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Duodenal Neoplasms; Female; Fluorouracil; Follow-Up Studies; Humans; Ileal Neoplasms; Intestine, Small; Irinotecan; Jejunal Neoplasms; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms; Prognosis; Retrospective Studies; Survival Rate

Free peritoneal tumor cells (FPTCs) are an independent prognostic factor in patients undergoing curative resection for gastric carcinoma. Whether neoadjuvant chemotherapy (NAC) can eliminate FPTCs in the peritoneal lavage remains unclear. The aim of the study was to determine the effect of NAC on FPTCs.. From 1994 to 2000, data from a total of 61 patients with resectable gastric cancer were analyzed. Peritoneal cytology was performed before NAC at laparoscopy and at tumor resection. A minimum of 6 weeks of NAC, consisting of cisplatin, folinic acid, and fluorouracil, was administered. FPTCs were detected immunohistochemically with Ber-EP4 antibody.. No FPTCs could be detected in 42 patients (69%), compared to 19 (31%) with FPTCs before NAC. During chemotherapy, 10 (24%) of 42 patients developed FPTCs, and 7 (37%) of 19 patients reverted from positive to negative. Patients who became FPTC negative (n = 7) showed an improved median survival (36.1 months) and a longer 2-year survival (71.4%) compared to FPTC-positive patients before and after NAC (n = 12), with a median survival of 9.2 months and a 2-year survival rate of 25%. In contrast, patients who reverted from FPTC negative to positive during NAC (n = 10) had a median survival of 18.5 months and a 2-year survival of only 20%. Multivariate analysis identified ypN category and FPTC change as independent prognostic factors.. NAC for patients with positive cytology could lead to FPTC negativity in a subset of patients and improve their prognosis. However, NAC might be a risky strategy for almost one-quarter of patients whose disease develops positive cytology.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Female; Fluorouracil; Follow-Up Studies; Humans; Intestinal Neoplasms; Laparoscopy; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Neoplastic Cells, Circulating; Peritoneal Cavity; Peritoneal Lavage; Peritoneal Neoplasms; Prospective Studies; Retrospective Studies; Stomach Neoplasms; Survival Rate; Treatment Outcome

Topics: Adenocarcinoma; Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Cecal Neoplasms; Cetuximab; Colectomy; Combined Modality Therapy; Diagnosis, Differential; Fluorouracil; Humans; Immunohistochemistry; Leucovorin; Lung Neoplasms; Male; Neoplasm Staging; Organoplatinum Compounds; Palliative Care; Peritoneal Neoplasms; Positron-Emission Tomography; Prognosis; Protein Kinase Inhibitors; Proto-Oncogene Proteins; Proto-Oncogene Proteins p21(ras); Pseudomyxoma Peritonei; ras Proteins; Whole Body Imaging

A treatment option for patients with peritoneal mucinous carcinomatosis (PMCA) from an appendiceal neoplasm is cytoreductive surgery and perioperative intraperitoneal chemotherapy. Also, these patients are recommended for systemic chemotherapy using an oxaliplatin and 5-fluorouracil (FOLFOX) regimen. A major question concerns the proper timing (neoadjuvant vs. adjuvant) of the systemic chemotherapy.. In January of 2005 a prospective study was initiated to routinely treat patients with peritoneal dissemination of a mucinous adenocarcinoma of the appendix with neoadjuvant chemotherapy using FOLFOX. All patients had a clinical, CT, intraoperative, and histopathological assessment of chemotherapy effects. The study was closed in July of 2009.. Thirty-four consecutive patients were available for evaluation. In the clinical evaluation and CT evaluation, 24 (71%) and 22 (65%), respectively, had stable disease on chemotherapy. By intraoperative examination 17 (50%) patients were observed to have progressed. By histopathology seven had a partial response and three patients a complete response (29%).. In these carcinomatosis patients clinical and CT assessment of response to neoadjuvant chemotherapy seldom provided useful data over this short time period. Intraoperative findings indicated progression in 50% of patients. By histopathology, 29% of patients had a response.

Topics: Adenocarcinoma, Mucinous; Antineoplastic Combined Chemotherapy Protocols; Appendiceal Neoplasms; Combined Modality Therapy; Female; Fluorouracil; Humans; Injections, Intraperitoneal; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Peritoneal Neoplasms

A58 -year-old man with sigmoid colon cancer with peritoneal dissemination was treated with bevacizumab (BV) plus mFOLFOX6 therapy as third-line chemotherapy after treatment failures with FOLFOX4 and FOLFIRI regimen. BV combination therapy resulted in a decrease in ascites and disappearance of the primary lesion. His ECOG performance status (PS) recovered from level 3 to level 1, and BV combination therapy improved his quality of life. This case suggested that BV in combination with chemotherapy could be a promising systemic chemotherapy for patients with colorectal cancer with peritoneal dissemination, and this regimen may be useful for patients progressing after receiving FOLFOX, FOLFIRI regimen.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Peritoneal Neoplasms; Sigmoid Neoplasms; Tomography, X-Ray Computed; Treatment Failure

We evaluate the long-term survival of patients with peritoneal carcinomatosis (PC) treated with systemic chemotherapy regimens, and the impact of the of the retrospective peritoneal disease severity score (PSDSS) on outcomes.. One hundred sixty-seven consecutive patients treated with PC from colorectal cancer between years 1987-2006 were identified from a prospective institutional database. These patients either received no chemotherapy, 5-FU/Leucovorin or Oxaliplatin/Irinotecan-based chemotherapy. Stratification was made according to the retrospective PSDSS that classifies PC patients based on clinically relevant factors. Survival analysis was performed using the Kaplan-Meier method and comparison with the log-rank test.. Median survival was 5 months (95% CI, 3-7 months) for patients who had no chemotherapy, 11 months (95% CI, 6-9 months) for patients treated with 5 FU/LV, and 12 months (95% CI, 4-20 months) for patients treated with Oxaliplatin/Irinotecan-based chemotherapy. Survival differed between patients treated with chemotherapy compared to those patients who did not receive chemotherapy (p = 0.026). PSDSS staging was identified as an independent predictor for survival on multivariate analysis [RR 2.8 (95%CI 1.5-5.4); p < 0.001].. A trend towards improved outcomes is demonstrated from treatment of patients with PC from colorectal cancer using modern systemic chemotherapy. The PSDSS appears to be a useful tool in patient selection and prognostication in PC of colorectal origin.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma; Chemotherapy, Adjuvant; Colorectal Neoplasms; Female; Fluorouracil; Germany; Health Status Indicators; Humans; Irinotecan; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Patient Selection; Peritoneal Neoplasms; Predictive Value of Tests; Proportional Hazards Models; Retrospective Studies; Risk Assessment; Risk Factors; Severity of Illness Index; Survival Rate; Time Factors; Treatment Outcome

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

Effective systemic therapy for advanced pseudomyxoma peritonei (PMP) is the focus of investigation. We describe a case of PMP arising from an adenoma of the appendix in a 58-year-old man. First, the patient underwent explorative laparotomy with ileocoecal resection, but without possibility of major tumor debulking due to adhesive gross tumor masses. Subsequently, six cycles of Folfox IV chemotherapy were administered, without response, but with severe side effects. Upon progressive disease, a combination of bevacizumab and capecitabine led to a long term stabilization of disease and obvious improvement of performance status. Our case suggests that modulation of tumor microenvironment and angiogenesis by bevacizumab, potentially augmented by moochemotherapy, may be beneficial in borderline tumors such as PMP.

Topics: Adenoma, Villous; Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Appendiceal Neoplasms; Bevacizumab; Capecitabine; Combined Modality Therapy; Deoxycytidine; Disease Progression; Fluorouracil; Hernia, Inguinal; Humans; Ileocecal Valve; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Peritoneal Neoplasms; Pseudomyxoma Peritonei; Treatment Outcome

We report on a remarkable diagnostic work up of suspect rectal palpation results in a 54-year-old patient. According to a transrectal ultrasound-guided punch biopsy the patient was suspected of having a carcinoma of the seminal vesicles and an aggressive operational approach was considered. After a median laparotomy a generalized peritoneal carcinomatosis was found. A goblet cell carcinoid of the vermiform appendix was identified as the primary tumor. This case report deals with metastazation of a primary goblet cell carcinoma into the seminal vesicles on both sides as an extremely rare reason for suspicious rectal palpation results. The tumor valency, diagnostic work up, therapy and further differential diagnoses are described.

Topics: Antineoplastic Combined Chemotherapy Protocols; Appendectomy; Appendiceal Neoplasms; Appendix; Biomarkers, Tumor; Biopsy; Carcinoid Tumor; Combined Modality Therapy; Diagnosis, Differential; Digital Rectal Examination; Fluorouracil; Genital Neoplasms, Male; Humans; Leucovorin; Magnetic Resonance Imaging; Male; Middle Aged; Organoplatinum Compounds; Palliative Care; Patient Care Team; Peritoneal Neoplasms; Seminal Vesicles; Synaptophysin

Although peritoneal dissemination of gastric cancer is common and often causes deterioration of the patient's condition and quality of life (QOL), these patients are usually excluded from clinical trials. We retrospectively investigated the clinical benefit and toxicity of sequential methotrexate and 5-fluorouracil (MTX/5FU) therapy for patients with peritoneal dissemination.. The subjects were 31 patients with severe peritoneal dissemination of gastric cancer who were treated with MTX/5FU. The treatment schedule comprised weekly administration of MTX (100 mg/m(2)) followed by 5FU (600 mg/m(2)). Leucovorin (10 mg/m(2)) was administered six times, every 6 h, starting 24 h after MTX administration.. The median survival time was 255 days, and the median progression-free survival was 127 days. Of the 21 patients with measurable lesions, 4 (19%) patients achieved a partial response. Ascites volume decreased markedly in 14 (54%) of the 26 patients with ascites. Seventeen patients had adequate oral intake, but the other 14 patients had required nutritional support before treatment. The median dripinfusion free survival was 100 days in the former 17 patients, and oral intake improved in 3 (21%) of the latter 14 patients. Grade 3 or 4 neutropenia was observed in 26% of the patients and anemia was observed in 45%. The grade 3 nonhematological toxicities were vomiting (6%) and fatigue (10%). Early death, within 30 days of the last administration of MTX/5FU, occurred due to disease progression in 2 patients, but there were no treatment-related deaths.. MTX/5FU chemotherapy may be effective in treating peritoneal dissemination of gastric cancer and might improve the patient's condition in terms of reducing ascites and improving oral intake.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Ascites; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Peritoneal Neoplasms; Quality of Life; Retrospective Studies; Severity of Illness Index; Stomach Neoplasms; Survival Rate; 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

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

To present our clinical experience of 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX4) regimen administered as an adjuvant chemotherapy to 2 patients with advanced jejunal adenocarcinoma.. A 55-year-old woman presented with recurrent upper abdominal pain, nausea and vomiting. A small bowel series as well as the abdominal computed tomography scan revealed an irregular narrowing lesion at the proximal jejunum. The patient then underwent an exploratory laparotomy and the jejunal adenocarcinoma with localized peritoneal metastasis was found (R0 resection, T3N1M1, stage IV). Chemotherapy with FOLFOX4 regimen of 12 cycles was initiated after the curative resection. No adverse event was observed during the period of chemotherapy. She has been well without evidence of recurrence for over 20 months postoperatively. The second case was a 77-year-old female presenting with mechanical ileus. Surgical exploration revealed a proximal jejunal adenocarcinoma with regional lymph node involvement (R0 resection, T3N1M0, stage III). She also received the FOLFOX4 chemotherapy of 12 cycles with an uneventful course. No obvious toxicity developed except for temporary grade I peripheral neuropathy and skin eruption. This patient has survived well and has been free of this disease for over 12 months since the operation.. This report showed that adjuvant chemotherapy with FOLFOX4 regimen seems effective and well tolerated in these 2 patients with advanced jejunal adenocarcinoma. Further investigation of a large number of patients with long-term follow-up is needed to confirm these findings.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Female; Fluorouracil; Humans; Jejunal Neoplasms; Leucovorin; Middle Aged; Organoplatinum Compounds; Peritoneal Neoplasms

In patients with metastatic colorectal cancer (mCRC), several prognostic factors such as performance status (PS), number of metastatic sites, carcinoembryonic antigen (CEA), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) have been reported. The objective of this study was to clarify the prognostic impact of Baseline Sum of Longest Diameter (BSLD) of target lesions by Response Evaluation Criteria in Solid Tumor (RECIST) in patients with mCRC.. The subjects of this study were consecutive 103 patients with mCRC who had been received the first line systemic chemotherapy between September 2002 and March 2005.. The chemotherapy regimens included leucovorin-modulated 5-fluorouracil (5-FU) (n = 27) and 5-FU plus irinotecan (n = 76). The median overall survival time was 547 days. The median BSLD was 14.3 cm (range, 1.1-54.7). In univariate analysis, identified prognostic variables on survival were PS (0, 1 versus 2), number of metastatic sites (1 versus >1), peritoneal dissemination (+ versus -), pleural effusion (PE) and/or ascites, white blood cell (> or = versus <10,000/mm(3)), ALP (> or = versus <300 IU), LDH (> or = versus <300 IU), CEA (> or = versus <5 ng/ml), chemotherapy regimen, presence of liver metastasis, and BSLD. In multivariate analysis with covariates of the above significant factors, BSLD (> or = versus <10 cm) (HR 0.431, 95% CI 0.237-0.785, P = 0.0059), PS (HR 0.248, 95% CI 0.107-0.577, P = 0.0012), PE and/or ascites (HR 0.402, 95% CI 0.228-0.708, P = 0.0016) were independent prognostic factors.. BSLD of target lesions by RECIST representing tumor volume might be an independent prognostic factor of patients with mCRC after systemic chemotherapy.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Camptothecin; Colorectal Neoplasms; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Male; Middle Aged; Peritoneal Neoplasms; Prognosis; Retrospective Studies; Survival Rate; Treatment Outcome

We reported a case of super-elderly colon cancer with peritoneal dissemination effectively treated with modified FOLFOX6 chemotherapy. A 80-year-old woman was referred to our hospital for abdominal distension in January 2007. Abdominal CT showed peritoneal dissemination and colonoscopy revealed transverse colon cancer. The patient's performance status (PS) score was 3. She had pleural effusion on the left side and massive acsites. After the general condition was improved, operation was performed for sub-ileus in March, but it became a probe laparotomy for severe peritoneal dissemination. We tried modified FOLFOX6 chemotherapy from April. The patient's pleural effusion decreased after 3 courses of chemotherapy and we could remove the thoracic tube. Massive acsites observed in abdominal CT disappeared after 5 courses of chemotherapy. The patient did not suffer from sub-ileus after around 8 courses of chemotherapy and she could then take food. The patient's PS score became 1, and she was discharged in September. Two more courses of chemotherapy were given on as an outpatient basis. The chemotherapy was changed to S-1 on the patient's request in November. As of February 2008, the patient's PS score was 0, and she has been under treatment as an outpatient.

Topics: Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoembryonic Antigen; Colonic Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Organoplatinum Compounds; Peritoneal Neoplasms; Tomography, X-Ray Computed

Pseudomyxoma peritonei (PMP) is a rare condition characterized by mucinous tumors, disseminated intra-peritoneal implants, and mucinous ascites. So far its diagnosis remains challenging to most clinicians.. A 55-year-old male patient had suffered from acute onset of abdominal pain and abdominal distension for one day prior to his admission. Physical examination revealed tenderness over the right lower quadrant of the abdomen without diffuse muscle guarding. A large amount of ascites was identified by abdominal computed tomography (CT) scan. Paracentesis showed the appearance of sticky mucinous ascites. He underwent laparotomy under the impression of pseudomyxoma peritonei. There was a lot of mucinous ascites, one appendiceal tumor and multiple peritoneal implants disseminated from the subphrenic space to the recto-vesicle pouch. Pseudomyxoma Peritonei caused by mucinous adenocarcinoma of appendiceal origin, was confirmed by histopathology. We performed an excision of the appendiceal tumor combined with copious irrigation and debridement. After the operation, he received 10 cycles of systemic chemotherapy with FOLFOX4 regimen, without specific morbidity. Follow-up of abdominal CT and colonoscopy at post-operative 17 months showed excellent response without evidence of local recurrence or distal metastasis. He made an uneventful recovery (up to the present) for 21 months after the operation.. This case report emphasizes the possible new role of systemic chemotherapy in the treatment of patients with this rare clinical syndrome.

Topics: Adenocarcinoma, Mucinous; Antineoplastic Combined Chemotherapy Protocols; Appendiceal Neoplasms; Chemotherapy, Adjuvant; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms; Pseudomyxoma Peritonei; Tomography, X-Ray Computed

A 62-year-old woman complained of thin feces, lower blood and abdominal pain, and she was diagnosed as having bowel obstruction due to sigmoid colon cancer. Abdominal CT showed peritoneal dissemination and ascites on the surface of liver. The serum CEA levels were 663.7 ng/mL. We established a diagnosis of unresectable sigmoid colon cancer accompanied by severe peritoneal dissemination and therefore performed only transverse colostomy in April, 2006. Pathological examination of omental dissemination demonstrated moderately-differentiated adenocarcinoma. FOLFOX4 therapy was started on April, 2006. Primary lesion decrease and release from bowel obstruction after 4 cycles was judged as a partial response. The partial response continued, and the serum CEA decreased 18.5 ng/mL after completion of 16 cycles, but grade 3 neuropathy occurred. We started S-1 as second-line chemotherapy in May, 2007. There was primary lesion re-growth after 4 cycles, so we changed to S-1+CPT-11 therapy. The adverse events were grade 3 neuropathy and leucopenia throughout the course. Chemotherapy is now continued on an outpatient basis, 24 months after the medical treatment started. FOLFOX4 therapy is useful for patients with advanced colon cancer accompanied by peritoneal dissemination.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoembryonic Antigen; Female; Fluorouracil; Humans; Leucovorin; Magnetic Resonance Imaging; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Peritoneal Neoplasms; Sigmoid Neoplasms; Tomography, X-Ray Computed

The modern treatment of pseudomyxoma peritonei is cytoreductive surgery plus intraperitoneal chemotherapy resulting in a survival of up to 70 percent after 20 years. The goal of this study was to investigate the impact on quality of life of this very aggressive treatment, which has not been done before.. Twenty-three prospective patients underwent cytoreductive surgery and early postoperative intraperitoneal chemotherapy for pseudomyxoma peritonei. Patients were followed in clinic 3, 6, 12, 18, and 24 months after surgery and had CT scan of the abdomen every 6 months. Quality of life was prospectively assessed with the generic quality of life instrument Short Form-36 Questionnaire, together with the two symptom-specific instruments--European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30, and Colorectal Cancer Module 38--before surgery and at every postoperative visit.. Complete cytoreduction was achieved in 21 patients. No patients died within 30 days. Seventy percent of patients had one or more complications during or after surgery, but all had recovered. Fourteen percent had an asymptomatic recurrence detected within two years. The impact on quality of life of the disease and of its treatment was very modest despite the high morbidity after the treatment. There was a significant decrease in the scores on the Short Form-36 Questionnaire scales of physical dimension and role physical three months after surgery, only returning to normal after another three months. The other scores corresponded to the scores in a normal population.. Cytoreductive surgery plus early postoperative intraperitoneal chemotherapy is an extensive treatment with a high morbidity but with relatively little impact on quality of life in patients with pseudomyxoma peritonei.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Peritoneal Neoplasms; Prospective Studies; Pseudomyxoma Peritonei; Quality of Life; Statistics, Nonparametric; Survival Rate; Treatment Outcome

Peritoneal metastases are common in metastatic disease of many tumour types and thus are determinant for prognosis and development of tumour-related symptoms that jeopardise quality of life. Systemic chemotherapy has proven efficacious in improving both prognosis and quality of life in numerous tumour types and should therefore be considered as part of the treatment strategy--although there is no large body of data from predefined cohorts with"only peritoneal" manifestation. In further clinical trials therefore, improvement of systemic chemotherapy by integration of novel agents should be implemented in multimodal treatment approaches combining systemic treatment, cytoreductive surgery, and intraperitoneal treatment strategies.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Chemotherapy, Cancer, Regional Perfusion; Colonic Neoplasms; Combined Modality Therapy; Fluorouracil; Gastrointestinal Neoplasms; Humans; Infusions, Intravenous; Irinotecan; Leucovorin; Neoplasm Staging; Peritoneal Neoplasms; Prognosis; Quality of Life

A 56-year-old woman diagnosed with a poorly differentiated cecal adenocarcinoma with metastases to ovaries, omentum, and sigmoid colon went into remission after 12 cycles of infusional 5-fluorouracil, luecovorin, and oxaliplatin (FOLFOX-4 regimen). Thirteen months later, a pelvic recurrence was diagnosed, and the patient received nine cycles of FOLFOX-6 plus bevacizumab, resulting in a clinical complete response but the development of pancytopenia. Bone marrow biopsy was consistent with therapy-related acute myelogenous leukemia. Chromosome analysis showed structural rearrangements with partial deletions of the long arms of chromosomes 5, 7, 20, and 21, as well as trisomy of chromosome 8 and losses of chromosomes 3 and 11. Induction chemotherapy led to remission, but the patient died two months later from complications of colon cancer progression. It is likely that the leukemia was related to the oxaliplatin administration.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Cecal Neoplasms; Chromosome Deletion; Female; Fluorouracil; Humans; Leucovorin; Leukemia, Myeloid, Acute; Middle Aged; Omentum; Organoplatinum Compounds; Ovarian Neoplasms; Peritoneal Neoplasms; Sigmoid Neoplasms; Trisomy

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

Because of insufficient activity and high toxicity of current chemotherapy regimens in advanced gastric cancer (AGC), there is a need for newer regimens.. Twenty-five chemonaive patients with AGC have been treated with FOLFIRI regimen consisting of irinotecan 180 mg/m(2) over 30 min on day 1 combined with leucovorin 200 mg/m(2) over 2 h followed by 5-fluorouracil 400 mg/m(2) as bolus and 600 mg/m(2) as a 22-hour infusion on day 1 and 2. The treatment was administered every 14th day until progression or intolerable toxicity.. Twenty-five patients (17 male, 8 female; 22 patients with PS 0-1 and 3 patients with PS 2), median age 54 (range 25-77), received a total of 230 courses of chemotherapy (median 9; range 1-18). Objective responses were observed in 9 patients (36%), all being partial. Median progression-free survival, 1- and 2-year progression-free survival rates were 8.6 months, 28.4% and 15.3%, respectively. Median overall survival, 1- and 2-year overall survival rates were 11.6 months, 48.0% and 17.8%, respectively. As serious adverse events, grade 3-4 neutropenia was observed in 5 patients (20.0%), grade 3 diarrhea in 4 patients (16.0%). No treatment-related death occurred.. FOLFIRI regimen is an active regimen with acceptable toxicity for the treatment of AGC.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Disease-Free Survival; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Peritoneal Neoplasms; Stomach Neoplasms; Survival Rate

Early postoperative intraperitoneal chemotherapy (EPIC) and intraoperative peritoneal hypertermic chemotherapy (IPHC) are used in addition with cytoreductive surgery to treat with curative intent peritoneal carcinomatosis arising from colorectal adenocarcinomas. Three patients with such a disease were treated with perioperative intraperitoneal chemotherapy in addition to cytoreductive surgery and presented isolated local recurrence located in the inguinal canal (round ligament in two and spermatic cord in one). All these patients were treated by local surgical excision. No patient showed evidence of intra-abdominal recurrence at the last follow-up, but one developed pulmonary metastasis. When communicating with the peritoneal cavity, the inguinal canal may act as a sanctuary site for peritoneal carcinomatosis, since it is not totally soaked by the intraperitoneal chemotherapy solution. A local recurrence is thus possible. New clinical presentations such as this one have first to be described in order to improve patient follow-up.

Topics: Adenocarcinoma, Mucinous; Adult; Antineoplastic Combined Chemotherapy Protocols; Appendiceal Neoplasms; Carcinoma; Cecal Neoplasms; Colectomy; Colonic Neoplasms; Combined Modality Therapy; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Parenteral; Inguinal Canal; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms; Tomography, X-Ray Computed

5-FU/LV therapy has been standard chemotherapy for advanced and recurrent colorectal cancer. Several studies reported that a new alternative chemotherapy, UFT/LV, had anti-cancer effects the same as with conventional 5-FU/LV therapy. We report a patient who had advanced and recurrent colorectal cancer treated with UFT/ LV. This 70-year-old male was admitted to our hospital because of a right lower abdominal mass, which was diagnosed as a peritoneal recurrence of transverse colon cancer by abdominal CT. UFT/LV therapy was started on an outpatient basis. After one course of chemotherapy, the intra-abdominal mass disappeared, and this therapy was continued for three courses. He did not suffer from any adverse effect during chemotherapy. Although this therapy was resumed because of the recurrence at the same site after nine months, it was refractory to chemotherapy. Thereafter, surgical resection was performed, and it was diagnosed as lymph node metastasis of previous surgery.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Combined Modality Therapy; Drug Administration Schedule; Humans; Leucovorin; Male; Peritoneal Neoplasms; Tegafur; Uracil

A 57-year-old woman underwent right hemicolectomy (D3) due to transverse colon cancer with multiple liver and peritoneal metastasis. Administration of oral UFT+Leucovorin was started postoperatively. After 6 months, the multiple liver metastases completely disappeared without any adverse reaction. After 14 months, no other recurrence was found by CT scan. This case suggests the usefulness of oral UFT+Leucovorin for progressive recurrent colorectal cancer as home chemotherapy.

Topics: Adenocarcinoma; Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Colectomy; Colonic Neoplasms; Combined Modality Therapy; Drug Administration Schedule; Female; Humans; Leucovorin; Liver Neoplasms; Middle Aged; Peritoneal Neoplasms; Quality of Life; Remission Induction; Tegafur; Uracil

Jejunal adenocarcinoma is rare, often presenting late with widespread intraperitoneal disease. Intraperitoneal chemotherapy (IPC) has been shown in non-randomized studies to improve the survival of patients presenting with intraperitoneal metastases from carcinoma of the colon, appendix and stomach and in primary peritoneal malignancies including mesothelioma and pseudomyxoma peritonei, providing that adequate operative cytoreduction can be performed. A case is presented of obstructive jejunal adenocarcinoma in which 19 intraperitoneal deposits were excised. The patient was treated successfully with immediate postoperative IPC followed by systemic chemotherapy. This condition is reviewed along with the rationale for IPC.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Infusions, Parenteral; Intestinal Obstruction; Jejunal Neoplasms; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Peritoneal Neoplasms

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

The patient is a 66-year-old male who underwent gastrojejunostomy at another hospital with the diagnosis of type 3 unresectable gastric cancer. He was admitted to our hospital for adjuvant chemotherapy. A CT scan revealed both peritoneal dissemination and a large tumor directly invading the pancreas and liver. After 7 courses of combined chemotherapy with 5-FU, Leucovorin, cis-platinum and methotrexate, an effective response, tumor reduction and the disappearance of peritoneal dissemination, was verified by CT scan. Pancreatoduodenectomy with transverse colectomy was carried out and the pathological diagnosis was also curative (pT3, pN1, pP0, HO: stage III A). Although he unfortunately died from peritoneal recurrence after 9 months, he maintained good quality of life after re-operation. We think this case shows the possibility of NAC for patients with far advanced gastric cancer with peritoneal dissemination to improve their prognosis or QOL.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Fluorouracil; Gastrectomy; Humans; Jejunostomy; Leucovorin; Liver Neoplasms; Lymphatic Metastasis; Male; Methotrexate; Neoadjuvant Therapy; Neoplasm Invasiveness; Pancreatic Neoplasms; Peritoneal Neoplasms; Quality of Life; Stomach Neoplasms

We report a case in which l-leucovorin/5-fluorouracil (l-LV/5-FU) combination therapy was remarkably effective for non-resectable advanced descending colon cancer with carcinomatous peritonitis. A 65-year-old man complained of severe abdominal distension, abdominal pain and pulmonary failure, and was diagnosed as having ileus due to descending colon cancer. The patient underwent urgent open laparotomy to release the ileus condition on March 5, 2002. During the laparotomy, we established a diagnosis of nonresectable descending colon cancer accompanied by severe peritoneal dissemination and therefore performed only double-barreled transverse colostomy. The postoperative course was very good. Pathological examination of omental dissemination demonstrated moderately differentiated adenocarcinoma and cytology of ascites was class II. The levels of serum CEA and CA19-9 were within the normal ranges. l-LV/5-FU therapy was initiated postoperatively. Seven cycles of this chemotherapy regimen was performed with no apparent side effect during the treatment. There was no postoperative accumulation of carcinomatous ascites. The patient gained 15 kg compared with body weight admission. On abdominal computed tomography (CT), the primary lesion of the colon decreased 98% and there was no ascites found. To date, there has not been any sign of recurrence during the 19 months of follow-up after this therapy, and we are currently discussing closure of the transverse colostomy. This therapy may be useful for patients with advanced colon cancer accompanied by peritoneal dissemination.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Dose-Response Relationship, Drug; Drug Administration Schedule; Fluorouracil; Humans; Leucovorin; Male; Peritoneal Neoplasms; Quality of Life

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Peritoneal Neoplasms; Peritoneum; Pseudomyxoma Peritonei

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 66-year-old man underwent a curative operation for cecal cancer on the 30th of November, 1998. Since his CEA level rose in January 2001, computed tomography (CT) revealed a tumor in the abdomen. He underwent a resection of this tumor and disseminated tumors that were diagnosed during the operation. He received systemic chemotherapy (5'-DFUR 600 mg 3x everyday, CPT-11 80 mg/body div every 2 weeks), but the CEA level rose again in August 2003. He was diagnosed with spleen metastasis and underwent splenectomy. The tumor disseminated in the left diaphragm was also resected. After that, he received systemic chemotherapy (5-FU 500 mg/body/week div, levofolinate calcium 250 mg/body/week i.v.) as an outpatient. Peritoneal carcinomatosis from colorectal cancer with distant metastasis, in general, has no indication for an operation. However, if dissemination is located after a sufficient observation period, its resection may be recommended.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoembryonic Antigen; Cecal Neoplasms; Combined Modality Therapy; Floxuridine; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Neoplasm Seeding; Peritoneal Neoplasms; Reoperation

Dihydropyrimidine dehydrogenase (DPD) is an enzyme that catabolizes 5-fluorouracil (5-FU). The effect of DPD inhibitory fluoropyrimidines (DIF) is presumably related to DPD activity. We studied the efficacy of DIF (tegafur + uracil UFT], tegafur + gimeracil + osteracil [S-1 (TS-1)]) relative to DPD activity, with other fluoropyrimidines as controls.. The efficacy of DIF relative to DPD activity was evaluated in 58 gastric cancer patients who received postoperative administration of fluoropyrimidines, consisting of DIF in 42 patients (UFT in 23; S-1 in 19) and non-DIF in 16 patients.. In patients with low DPD activity (under 40 U/mg protein), curative potential tended to be lower for DIF than for non-DIF, but the survival rate was the same for both. In patients with high DPD activity (40 U/mg protein or more), such a tendency was not detected. In a comparison between those treated with UFT and those treated with S-1, prognosis was better in the latter group, in spite of their predominance of lower curative potentials of B or C. In 27 patients with measurable lesions, a partial response (PR) or higher response occurred in 33% (5/15) of those with low DPD activity, and in 17% (2/12) of those with high DPD activity. In the patients with low DPD activity, non-DIF induced no change (NC) in 17% (16), and progressive disease (PD) in the rest. UFF induced PD in all 5 patients, while S-1 induced a response rate of 44% (7/16), with NC in 25% (4/16). In the patients with high DPD activity, on the other hand, non-DIF (n = 3) and UFT (n = 3) induced PD in all the patients, while S-1 induced PR in 33% (2/6) and NC or a higher response in 67% (4/6).. It is recommended to use S-1 rather than UFF in patients with high DPD activity. Measurement of DPD was useful in drug selection.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Dihydrouracil Dehydrogenase (NADP); Disease Progression; Drug Combinations; Enzyme Inhibitors; Fluorouracil; Humans; Japan; Leucovorin; Liver Neoplasms; Lymphatic Metastasis; Oxidoreductases; Oxonic Acid; Peritoneal Neoplasms; Prognosis; Pyridines; Statistics as Topic; Stomach Neoplasms; Survival Analysis; Tegafur; Treatment Outcome; Uracil

Afferent loop syndrome (ALS) is a debilitating complication of recurrent gastric cancer. Surgical intervention is usually not feasible in the face of poor general performance, presence of advanced peritoneal carcinomatosis and limited survival of the patients. Non-surgical approaches include internal drainage by stenting at the stenotic or anastomotic site and external drainage via the percutaneous routes. Percutaneous transhepatic duodenal drainage (PTDD) has been shown to provide effective palliation for ALS, but long-term catheterization is usually inevitable. We hereby present two cases of recurrent gastric cancer whose ALS was successfully treated with PTDD followed by weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin (HDFL). PTDD rapidly ameliorated the incapacitating symptoms of ALS, and the effective, low-toxicity chemotherapy subsequently led to tumor regression, restoration of bowel patency and removal of the drainage tube. At present, both patients have remained ALS-free and drainage-free for 16 and 17 months, respectively. Our results indicate that this non-surgical approach with PTDD followed by weekly HDFL could serve as a safe and effective treatment for ALS in recurrent gastric cancer complicated by peritoneal carcinomatosis.

Topics: Adenocarcinoma; Afferent Loop Syndrome; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Combined Modality Therapy; Dose-Response Relationship, Drug; Drainage; Fluorouracil; Follow-Up Studies; Gastrectomy; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Palliative Care; Peritoneal Diseases; Peritoneal Neoplasms; Stomach Neoplasms; Treatment Outcome

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

Pseudomyxoma peritonei remains a fatal disease. However, extensive surgical cytoreduction combined with intraoperative heated intraperitoneal chemotherapy (HIPEC) has recently emerged as a new treatment modality, which might improve survival.. Patients underwent treatment if the tumour appeared to be technically resectable on preoperative abdominal computed tomography and there were no distant metastases. After aggressive surgical cytoreduction, HIPEC with the administration of mitomycin C was performed for 90 min. Depending on histological grading, patients received adjuvant 5-fluorouracil and leucovorin therapy.. Forty-six patients were treated. Optimal surgical cytoreduction was obtained in 40 patients. Postoperative surgical complications occurred in 18 patients. Four patients died as a direct result of the treatment. Bone marrow suppression due to mitomycin C toxicity occurred in 22 patients. There was no other major toxicity related to the HIPEC procedure. After a median follow-up of 12 months, 40 patients are alive, eight of whom have proven recurrence. The actuarial survival rate (Kaplan-Meier) at 3 years was 81 per cent.. These results confirm that extensive surgery combined with HIPEC is feasible in patients with pseudomyxoma peritonei and that improved long-term survival might be achieved.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Chemotherapy, Cancer, Regional Perfusion; Female; Fluorouracil; Follow-Up Studies; Humans; Hyperthermia, Induced; Infusions, Intravenous; Injections, Intravenous; Length of Stay; Leucovorin; Male; Middle Aged; Mitomycin; Neoplasm Recurrence, Local; Peritoneal Neoplasms; Postoperative Complications; Pseudomyxoma Peritonei; Reoperation; Treatment Outcome

We treated a patient with intra-peritoneal recurrent tumor from colon cancer who responded completely to chemotherapy of combined low-dose Leucovorin (LV) and 5-fluorouracil (5-FU). The patient was a 75-year-old man. He underwent resection of the transverse colon, sigmoid colon and distal stomach for colon and gastric cancers. Nine months after the operation, his CEA level increased to 39.5 ng/ml and a CT scan revealed an intra-peritoneal tumor measuring about 5 cm. He received chemotherapy of 30 mg/day of LV that was injected in a bolus and 500 mg/day of 5-FU that was given i.v. by continuous infusion for 10 days. At the end of 2 cycles of this regimen, CT scan demonstrated complete tumor remission and the patient's CEA level decreased to normal level. After an additional cycle of this regimen, he received modulated chemotherapy combined with l-Leucovorin and 5-FU as an outpatient. However, after 3 months of treatment, a recurrent tumor was detected in the same portion and the first regimen was re-started for 5 days. After 4 cycles of treatment the tumor disappeared completely from a CT scan. It is important to investigate effective regimens that do not reduce the quality of life of the patient. This clinical experience suggests that a low-dose LV/5-FU therapy may be beneficial to patients with recurrent colon cancer. Further investigation is necessary to establish an effective regimen that can be given for a long period without adverse effects on quality of life.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Drug Administration Schedule; Fluorouracil; Humans; Leucovorin; Male; Peritoneal Neoplasms

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Appendiceal Neoplasms; Colonic Neoplasms; Combined Modality Therapy; Floxuridine; Formyltetrahydrofolates; Humans; Infusions, Parenteral; Leucovorin; Peritoneal Neoplasms; Survival Rate

Aggressive treatment of peritoneal metastases from colon cancer by surgical cytoreduction and infusional intraperitoneal (IP) chemotherapy may benefit selected patients. We reviewed our institutional experience to assess patient selection, complications, and outcome.. Patients having surgical debulking and IP 5-fluoro-2'-deoxyuridine (FUDR) plus leucovorin (LV) for peritoneal metastases from 1987 to 1999 were evaluated retrospectively.. There were 64 patients with a mean age of 50 years. Primary tumor sites were 47 in the colon and 17 in the appendix. Peritoneal metastases were synchronous in 48 patients and metachronous in 16 patients. Patients received IP FUDR (1000 mg/m2 daily for 3 days) and IP leucovorin (240 mg/m2) with a median cycle number of 4 (range, 1-28). The median number of complications was 1 (range, 0-5), with no treatment related mortality. Only six patients (9%) required termination of IP chemotherapy because of complications. The median follow-up was 17 months (range, 0-132 months). The median survival was 34 months (range, 2-132); 5-year survival was 28%. Lymph node status, tumor grade, and interval to peritoneal metastasis were not statistically significant prognostic factors for survival. Complete tumor resection was significant on multivariate analysis (P = .04), with a 5-year survival of 54% for complete (n = 19) and 16% for incomplete (n = 45) resection.. Surgical debulking and IP FUDR for peritoneal metastases from colon cancer can be accomplished safely and has yielded an overall 5-year survival of 28%. Complete resection is associated with improved survival (54% at 5 years) and is the most important prognostic indicator.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Appendiceal Neoplasms; Colonic Neoplasms; Combined Modality Therapy; Female; Floxuridine; Formyltetrahydrofolates; Humans; Infusions, Parenteral; Leucovorin; Male; Middle Aged; Peritoneal Neoplasms; Retrospective Studies; Survival Analysis

Topics: Adrenal Cortex Hormones; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Fluorouracil; Histamine H1 Antagonists; Humans; Hypotension; Infusions, Intravenous; Leucovorin; Liver Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms

A 78-year-old woman was admitted to our hospital for the control of gallbladder cancer. A peritoneal metastasis, diagnosed as unresectable cancer, was detected during surgery in a previous hospital, and a biliary stent was introduced and gastrojejunostomy was performed. In our hospital she was treated weekly with local chemotherapy (PFL; cisplatin 2.5-5 mg/body ia, fluorouracil 300 mg/body ia, and calcium folinate 30 mg/body ia, via the common hepatic arterial port) at the time of hyperthermia. Hyperthermia was performed with a Thermox 500 (HEH-500 C) at the power of 500 watts for 45-60 minutes. To enhance the hyperthermia effect, mitomycin C 2-4 mg/body ia via the common hepatic arterial port and 500 ml of 7.5% glucose infusion were given. As a result of the combination therapy, the volume of the whole tumor was reduced to 60.9% on computed tomography, and diagnosed as PR. The serum level of CA19-9 decreased from 3,000 U/ml to 300 U/ml. The patient continued to receive the therapy for 1 year, and is now well. Therefore, we conclude that combination therapy with hyperthermia and local chemotherapy seems beneficial in managing unresectable advanced gallbladder cancer, especially for the elderly.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Female; Fluorouracil; Gallbladder Neoplasms; Humans; Hyperthermia, Induced; Leucovorin; Mitomycin; Peritoneal Neoplasms

A 68-year-old man underwent curative pancreaticoduodenectomy for bile duct cancer. The histological diagnosis was well differentiated, invasive type tubular adenocarcinoma, which was 2 x 2 cm in size and had invaded to the adventitia. Lymph node metastasis was not present. The postoperative course was uneventful, but lymph node and peritoneum metastases were detected 18 months after surgery. Chronochemotherapy of 5-FU (500 mg/body), leucovorin (21 mg/body), mitomycin C (2 mg/body) and cisplatin (80 mg/body) was performed without significant side effects. One course of chronochemotherapy was effective for lymph node and peritoneum metastases. The patient died of peritonitis carcinomatosa 10 months after recurrence.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Cisplatin; Drug Administration Schedule; Fluorouracil; Humans; Leucovorin; Lymph Nodes; Lymphatic Metastasis; Male; Mitomycin; Peritoneal Neoplasms

A 45-year-old woman was admitted to our hospital because of lower abdominal pain and anorexia. A barium gastrography and gastroscopy showed a type 4 gastric cancer in the upper gastric body. Histologic study on biopsy specimens from the tumor revealed poorly differentiated adenocarcinoma. Computed tomography revealed bilateral hydronephrosis, and barium enema showed diffuse stenosis of the sigmoid colon because of peritoneal dissemination. This patient was treated by intra-aortic infusion therapy with sequential MTX and 5-FU. After five courses of the administration, barium enema revealed reexpansion of the lumen of sigmoid colon with normalization of the tumor markers. The patient was discharged without symptoms. Intra-aortic infusion therapy with sequential MTX and 5-FU was considered an effective treatment for unresectable gastric cancer.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intra-Arterial; Leucovorin; Methotrexate; Middle Aged; Peritoneal Neoplasms; Stomach Neoplasms

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Doxorubicin; Drug Administration Schedule; Female; Fluorouracil; Gastrectomy; Humans; Infusions, Intravenous; Injections, Intravenous; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Mitomycin; Peritoneal Neoplasms; Preoperative Care; Prognosis; Stomach Neoplasms

The optimal schedule for the administration of 5-fluorouracil (5-FU) in the management of advanced colorectal cancer remains to be determined. It has been suggested that this drug may be given by the subcutaneous route and that following a short infusion the bioavailability is similar to that observed after intravenous administration. We report the results we obtained in a patient treated with an intravenous bolus of 5-FU followed by a 22-h subcutaneous infusion. In this patient the bioavailability of 5-FU given by subcutaneous infusion was 0.94. The steady-state plasma levels of 5-FU reached during subcutaneous infusion were comparable with those achieved during intravenous infusion. Following four cycles of subcutaneous therapy, painless blistering was noted at the infusion sites, which healed following the cessation of subcutaneous therapy. Further studies are required to evaluate this route of therapy as an alternative to protracted intravenous therapy. The main dose-limiting side effect appears to the local skin toxicity.

Topics: Antidotes; Antimetabolites, Antineoplastic; Biological Availability; Carcinoma; Colorectal Neoplasms; Fluorouracil; Humans; Injections, Intravenous; Injections, Subcutaneous; Leucovorin; Liver Neoplasms; Male; Middle Aged; Peritoneal Neoplasms; Skin

We reported a case of gastric cancer with peritoneal dissemination, which was successfully treated by neoadjuvant chemotherapy and partial gastrectomy. A 71-year-old female visited to our hospital because of umbilical tumor (Sister Mary Joseph's node). UGI series showed a Borrmann 1 type gastric cancer and laparoscopic examination revealed peritoneal metastasis. Her abdominal cavity was treated with MTX and CDDP and she was given intravenous administration of 5-FU/LV. Repeated laparoscopy revealed complete disappearance of peritoneal seeding, and a partial gastrectomy was done. The histopathological findings of resected specimen showed the significant effects of preoperative chemotherapy. She has been living for more than 2 years with no recurrence after initial chemotherapy.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Female; Fluorouracil; Gastrectomy; Humans; Leucovorin; Methotrexate; Peritoneal Neoplasms; Prognosis; Stomach Neoplasms; Tegafur; Uracil

We report on the atypical course of a 31-year old primigravida, who underwent conservative treatment for a tubal pregnancy. After confirmation of the diagnosis by means of laparoscopy, a linear salpingotomy and removal of the products of gestation were performed through the laparoscope. Routine measurements of the serum HCG levels postoperatively showed, after a short period of decreasing HCG levels, a new rapid increase of HCG values. At relaparoscopy, evidence for an intraperitoneal dissemination of trophoblastic tissue was found and confirmed by histology. After treatment with 20 mg methotrexate q.i.d. per os for 5 days, HCG levels returned to normal within a short time. Apart from a minor degree of an aphthosal stomatitis, the patient did not experience any major side effects from the treatment.

Topics: Adult; Biomarkers, Tumor; Biopsy; Chorionic Gonadotropin; Choristoma; Combined Modality Therapy; Female; Humans; Laparoscopy; Leucovorin; Methotrexate; Neoplasm Seeding; Peritoneal Neoplasms; Peritoneum; Postoperative Complications; Pregnancy; Pregnancy, Tubal; Salpingostomy; Trophoblasts

Twenty-five patients with advanced measurable gastric cancer were treated with high-dose folinic acid (200 mg/m2), 5-fluorouracil bolus (400 mg/m2) and continuous infusion (600 mg/m2) for two consecutive days every two weeks. Fourteen patients over 65 yr old and/or with a poor general status received first-line treatment, and eleven younger patients second-line. The response rate was 43.5% in 23 evaluable patients. There were 2 complete responses (8.7%) and 8 partial responses (34.8%). Median survival was 6 months in first-line and 8 months, calculated from start of folinic acid-5FU, in second-line. Toxicity was mild without WHO Grade greater than 2 events. This combination is effective for advanced gastric cancer in poor-prognosis patients and requires further studies.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Ovarian Neoplasms; Peritoneal Neoplasms; Prognosis; Stomach Neoplasms

The incidence of malignant mesothelioma has increased greatly in the last 40 years. Current and recent past exposure to asbestos is expected to substantially increase this incidence. We report nine cases of malignant mesothelioma which temporarily responded to treatment with high-dose methotrexate-citrovorum rescue and vincristine. Further clinical trials of high-dose methotrexate with citrovorum rescue appear indicated in this disease.

Topics: Adult; Aged; Asbestos; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Leucovorin; Leukopenia; Male; Mesothelioma; Methotrexate; Middle Aged; Peritoneal Neoplasms; Pleural Neoplasms; Time Factors; Vincristine