levoleucovorin and Lung-Neoplasms

Colorectal cancer is the second leading cause of cancer-related death worldwide. For metastatic colorectal cancer (mCRC) patients, it is recommended, as first-line treatment, chemotherapy (CT) based on doublet cytotoxic combinations of fluorouracil, leucovorin, and irinotecan (FOLFIRI) and fluorouracil, leucovorin, and oxaliplatin (FOLFOX). In addition to CT, biological (targeted agents) are indicated in the first-line treatment, unless contraindicated. In this context, most of mCRC patients are likely to progress and to change from first line to second line treatment when they develop resistance to first-line treatment options. It is in this second line setting where Aflibercept offers an alternative and effective therapeutic option, thought its specific mechanism of action for different patient's profile: RAS mutant, RAS wild-type (wt), BRAF mutant, potentially resectable and elderly patients. In this paper, a panel of experienced oncologists specialized in the management of mCRC experts have reviewed and selected scientific evidence focused on Aflibercept as an alternative treatment.

Topics: Age Factors; Angiogenesis Inhibitors; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Clinical Trials, Phase III as Topic; Colorectal Neoplasms; Drug Substitution; Fluorouracil; Genes, ras; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Mutation; Neovascularization, Pathologic; Organoplatinum Compounds; Proto-Oncogene Proteins B-raf; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Vascular Endothelial Growth Factor A

Efficacy and the frequency of tumor cavitation have not been investigated in patients with metastatic colorectal cancer (mCRC) and lung metastases (LMs) treated with chemotherapy in combination with bevacizumab. This study was aimed to evaluate the efficacy and safety of bevacizumab for unresectable mCRC with LM and to determine the frequency of tumor cavitation, and its correlation with clinical outcomes in patients receiving bevacizumab plus chemotherapy.. Patients with mCRC and LMs treated with bevacizumab as first- or second-line therapy at West China Hospital, Sichuan University Cancer Center from September 2010 to November 2016 were included in this retrospective study. Data on clinicopathological characteristic were collected and overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) were determined.. Among 60 patients included in the study, response rate (RR), stable disease (SD), and DCR were 43.6% (17/39), 51.3% (20/39) and 94.9% (37/39) in patients receiving bevacizumab as first-line treatment. Median OS and PFS of the first-line treatment group were 32.4 and 15.5 months, respectively. Among 60, 12 patients (20%) developed cavitation after bevacizumab therapy initiation. Median OS was longer in patients with cavitation than those without cavitation (42.1 vs 30.8 months; p = 0.042) in the first-line treatment group.. Bevacizumab in combination with chemotherapy exhibited promising efficacy in mCRC patients LMs. Moreover, our findings reveal that OS might be affected by new tumor cavitation during antiangiogenic agent treatment.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Capecitabine; Colorectal Neoplasms; Deoxycytidine; Female; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Oxaloacetates; Retrospective Studies

A 67-year-old man was diagnosed with pulmonary metastasis from advanced transverse colon cancer. Thus, a local resection was performed. Adjuvant chemotherapy with mFOLFOX6 was started. Sixteen courses were carried out without problems. However, he complained of chills and chest discomfort 2 hours after beginning the 17th course of chemotherapy. Laboratory data showed remarkable thrombocytopenia, and platelet-associated IgG level was high. After administration of steroids and platelet transfusions, the platelet count improved. Therefore, we diagnosed drug-induced thrombocytopenia resulting from sensitivity to oxaliplatin (L-OHP). Since then, sLV5FU2 therapy was started, and the patient received the whole adjuvant chemotherapy without problems. Thrombocytopenia resulting from sensitivity to L-OHP is a relatively rare side effect. We herein report this case with a review of the relevant literature.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colectomy; Colon, Transverse; Colonic Neoplasms; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Organoplatinum Compounds; Oxaliplatin; Platelet Transfusion; Pneumonectomy; Thrombocytopenia

Aflibercept, also known as vascular endothelial growth factor (VEGF)-Trap, is a recombinant, decoy receptor fusion protein, rationally designed to block angiogenesis by targeting not only all forms of VEGF-A, but also VEGF-B and placental growth factor. It inhibits VEGF-induced angiogenesis in preclinical models. In tumor models, aflibercept is associated with the reduction of tumor vasculature and size, and the inhibition of ascites formation. Clinical studies are investigating the use of aflibercept alone and in combination with other antineoplastic therapies for the treatment of various cancers. Phase I and II studies have provided proof of principle, and support the continuing clinical investigation of aflibercept. Results from the phase III study, VITAL, of aflibercept in the second-line setting in patients with advanced non-small cell lung cancer [NCT00532155] demonstrated efficacy in progression-free survival and overall objective response rate, but overall survival was not significantly improved. A full report awaits publication. The Phase III VANILLA trial in metastatic pancreatic cancer [NCT00574275] showed no improvement in overall survival. Most recently, the phase III VELOUR study [NCT00561470] of aflibercept plus FOLFIRI compared with placebo plus FOLFIRI in patients with metastatic colorectal cancer following failure of an oxaliplatin regimen showed significant improvements in overall survival, progression-free survival, and response rate and the complete results have been submitted to a peer-reviewed journal. This review summarizes preclinical and clinical data for aflibercept and discusses future directions and clinical trials for this agent.

Topics: Animals; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Carcinoma, Non-Small-Cell Lung; Clinical Trials as Topic; Colorectal Neoplasms; Disease-Free Survival; Drug Screening Assays, Antitumor; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Vascular Endothelial Growth Factor A

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

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

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

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

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

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

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

After over 30 years of theorizing, the use of angiogenesis inhibitors as anticancer therapy has finally moved from the realm of research to reality. Normal adult vasculature is generally quiescent in nature, with endothelial cells dividing approximately every 10 years. In contrast, the growth of tumours requires constant vascular growth and remodelling in order for solid tumours to grow beyond 1-2 mm3 in size. Vascular endothelial growth factor (VEGF) and its receptors are key regulators of the process of angiogenesis, which make them attractive therapeutic targets. A multitude of VEGF-targeted inhibitory agents are currently being investigated for the treatment of cancer. This review article focuses on recent developments in the use of angiogenesis inhibitors for the treatment of breast, lung, and colorectal cancers.

Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Breast Neoplasms; Camptothecin; Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms; Fluorouracil; Humans; Hypertension; Kidney Neoplasms; Leucovorin; Lung Neoplasms; Neoplasms; Neovascularization, Pathologic; Receptors, Vascular Endothelial Growth Factor; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Camptothecin; Cisplatin; Combined Modality Therapy; Deoxycytidine; Doxorubicin; Etoposide; Femoral Neoplasms; Gemcitabine; Head and Neck Neoplasms; Humans; Ifosfamide; Irinotecan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Methotrexate; Middle Aged; Neoadjuvant Therapy; Osteosarcoma; Palliative Care; Salvage Therapy; Scalp; Skin Neoplasms; Thoracotomy

New results presented at ASCO Conference in 2003 added further important data to our knowledge on successful use of irinotecan in colorectal cancer (CRC). Irinotecan - just like oxaliplatin - given as neoadjuvant therapy with 5-FU - folinic acid (FUFA) can render originally unresectable liver or lung metastases of CRC resectable, giving the hope of long-term survival for a proportion of patients. Irinotecan combined with 5-FU is an essential part of the most successful palliative sequential chemotherapy of stage IV CRC. Sequential FOLFIRI before or after FOLFOX combination ensures the longest possible progression-free and overall survival for metastatic CRC patients in the palliative setting. In order to achieve the longest survival time, sequential use of both 5-FU, irinotecan and oxaliplatin is necessary. The French GERCOR Group achieved 26 months median overall survival with the sequential use of continuous infusional FUFA, oxaliplatin and irinotecan combinations in stage IV CRC. The analysis of large phase III trials using 5-FU, irinotecan and oxaliplatin revealed that the higher proportion of patients was treated with all three drugs, the longer overall survival was achieved. If applied with caution, toxicity and efficacy of irinotecan in elderly patients is not significantly different from that seen in younger population. The anti-VEGF bevacizumab increases the efficacy of first-line irinotecan therapy, while the addition of cetuximab restores irinotecan sensitivity in second line treatment of stage IV CRC. The combination of irinotecan with oral capecitabine is safe and effective in advanced CRC.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Capecitabine; Cetuximab; Chemotherapy, Adjuvant; Clinical Trials, Phase III as Topic; Colorectal Neoplasms; Deoxycytidine; Disease-Free Survival; Fluorouracil; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaliplatin; Palliative Care; Survival Analysis; Treatment Outcome

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colectomy; Colorectal Neoplasms; Fluorouracil; Humans; Informed Consent; Irinotecan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Neoplasm Recurrence, Local

Topics: Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Neoplasm Recurrence, Local; Pain; Palliative Care; Practice Guidelines as Topic; Prognosis

Although 5-FU administered as a single agent in different intravenous bolus schedules has been shown to have minimal activity in non-small cell lung cancer (NSCLC), several lines of experimental evidence suggest that 5-FU in combination regimens may be synergistic with the 'anchor' drug of the combination. Moreover, the recent availability of oral formulations of 5-FU together with the ability to modulate the anabolic and catabolic metabolism of 5-FU with leucovorin and dihydropyrimidine dehydrogenase (DPD) inhibitors, respectively, may provide a substantial improvement in the ease of administration and the efficacy of fluoropyrimidine therapy. Several oral fluoropyrimidines are under investigation. Orzel [UFT (uracil:tegafur) plus oral leucovorin] is the first oral DPD-inhibitory fluoropyrimidine. Orzel administered daily achieves similar concentrations of 5-FU obtained with continuous-infusion 5-FU. This paper reviews the clinical experience with UFT and Orzel in the treatment of NSCLC.

Topics: Administration, Oral; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Clinical Trials as Topic; Drug Combinations; Humans; Leucovorin; Lung Neoplasms; Tegafur; Treatment Outcome; Uracil

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Clinical Trials as Topic; Colorectal Neoplasms; Combined Modality Therapy; Digestive System Neoplasms; Fluorouracil; Humans; Immunologic Factors; Interferon-alpha; Leucovorin; Lung Neoplasms; Neoplasm Staging; Neoplasms; Survival Analysis; Treatment Failure

UFT is an oral antineoplastic drug combining uracil and tegafur in a 4:1 molar ratio. Tegafur acts as a prodrug of 5-fluorouracil (5-FU), being slowly metabolized by cytochrome P450 to 5-FU. Uracil competitively inhibits the metabolism of 5-FU, resulting in increased plasma and tumor 5-FU concentrations. At equimolar doses, higher peak plasma 5-FU concentrations are achieved with UFT plus oral leucovorin with similar systemic 5-FU exposure compared with low-dose continuous 5-FU infusions. The elimination half-life of 5-FU following UFT administration is approximately 7 h compared with 0.2 h with i.v. 5-FU. In phase II studies of UFT plus oral leucovorin for the treatment of advanced colorectal cancer, response rates ranged from 25 to 42%. UFT plus oral leucovorin is well tolerated, with manageable diarrhea being the only dose-limiting toxicity; the regimen is not associated with significant myelosuppression, mucositis, hand-foot syndrome or alopecia. UFT, with or without leucovorin, has also been evaluated alone or in combination with other cytotoxic agents for the treatment of advanced lung, breast and gastric cancers. UFT has also been evaluated as adjuvant therapy for colorectal, breast, gastric, head and neck, and superficial bladder cancers. UFT plus leucovorin offers patients an entirely oral cancer treatment, and appears to provide potential advantages over bolus 5-FU regimens with regard to toxicity and convenience of administration. These benefits should be advantageous in the adjuvant setting, as well as in advanced disease settings in which palliation is an important consideration. Ongoing clinical trials will further define the role of this promising oral treatment regimen.

Topics: Administration, Oral; Antidotes; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Colorectal Neoplasms; Drug Combinations; Humans; Leucovorin; Lung Neoplasms; Neoplasms; Stomach Neoplasms; Tegafur; Uracil

Topics: Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Dactinomycin; Female; Humans; Hydatidiform Mole, Invasive; Leucovorin; Lung Neoplasms; Methotrexate; Middle Aged; Pregnancy; Uterine Neoplasms; Vincristine

Quality of life (QOL) variables are increasingly included as end points in cancer therapy trials, supplementing such traditional end points as survival time in evaluating the effects of cancer treatments. Consensus has been reached that a number of QOL components (symptom status and physical, emotional, role, and social functioning) should be measured. Assessing multiple health-related QOL dimensions, as compared with a global score, provides a more detailed accounting of specific effects of cancer treatment on patient functioning. Southwest Oncology Group QOL assessment policies emphasize patient reports and the need for systematic quality control procedures. The Southwest Oncology Group QOL questionnaire comprises a battery of categorical scales with established psychometric properties. A set of generic core scales is always included in the battery, and treatment- and disease-specific scales are developed for each trial. Other frequently used QOL questionnaires, such as the European Organization for Research and Treatment of Cancer QLQ-C30, the Cancer Rehabilitation Evaluation System questionnaire, and the Functional Assessment of Cancer Therapy are alternative instruments in current use. Quality of life findings from lung cancer clinical trials indicate a prevalence of symptom distress, fatigue, and decline in functional status, although patients also experience symptom management problems without treatment. A summary of preliminary QOL findings for two vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Médicament, Paris, France) trials (randomized and single-arm) in patients with non-small cell lung cancer show that symptom status was as good or better for patients receiving vinorelbine compared with those receiving 5-fluorouracil/leucovorin in the randomized study. Differences in other QOL dimensions were not detected. Findings for the single-arm trial of oral vinorelbine were generally consistent with those of the randomized trial.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Quality of Life; Randomized Controlled Trials as Topic; Vinblastine; Vinorelbine

Concomitant chemoradiotherapy represents an investigational approach to the treatment of locoregionally advanced non-small cell lung cancer. The theoretical rationale, and clinical experience are reviewed in brief. Clinical trials conducted at the University of Chicago are summarized.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chicago; Cisplatin; Clinical Trials as Topic; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Combined Modality Therapy; Fluorouracil; Humans; Hydroxyurea; Immunologic Factors; Interferon-alpha; Leucovorin; Lung Neoplasms; Pilot Projects; Randomized Controlled Trials as Topic; Treatment Outcome

5-Fluorouracil (5-FU) modulation with either folinic acid (FA) or methotrexate (MTX) has improved 5-FU's potential cytoreductivity. We combined MTX and FA with 5-FU to further augment 5-FU's cytoreductivity. Patients (n = 34) with advanced colorectal carcinoma were first given intravenous MTX (escalated from 30 mg/m2 to 70 mg/m2). FA (100 mg/m2) was infused 17-24 hr later, followed by 5-FU (600 mg/m2). Oral rescue doses of FA were begun 24 hr after MTX. Patients were treated every 2 weeks. No previously treated patient (n = 6) responded. Eight of the remaining 28 (29%) (95% confidence interval, 15-47%) patients achieved a PR. Median survival was 9.3 months. Toxicity (primarily gastrointestinal) necessitated dosage modification in 10 patients (29%). These results, in addition to a literature review, reveal that the manipulation of 5-FU by two modulating agents does not improve the response rate seen with single-agent modulation.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Colorectal Neoplasms; Diarrhea; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Methotrexate; Middle Aged; Remission Induction; Survival Rate; Treatment Outcome

Topics: Amputation, Surgical; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Chemotherapy, Adjuvant; Combined Modality Therapy; Cyclophosphamide; Disarticulation; Doxorubicin; Europe; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Neoplasm Recurrence, Local; Osteosarcoma; Survival Analysis; Treatment Outcome; Vincristine

Topics: Amputation, Surgical; Bone Neoplasms; Chemotherapy, Adjuvant; Child; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Humans; Ifosfamide; Leucovorin; Lung Neoplasms; Mesna; Osteosarcoma; Survival Analysis; Tennessee; Treatment Outcome; Vincristine

Topics: Administration, Oral; Animals; Biological Transport; Central Nervous System; Drug Resistance; Folic Acid; Folic Acid Antagonists; Gene Amplification; Head and Neck Neoplasms; Humans; Kinetics; Leucovorin; Leukemia, Lymphoid; Lung Neoplasms; Methotrexate; Neoplasms; Osteoma, Osteoid; Thymidylate Synthase; Tissue Distribution

Topics: Antineoplastic Agents; Bone Marrow; Bone Marrow Transplantation; Carcinoma, Small Cell; Clinical Trials as Topic; Drug Therapy, Combination; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Recurrence; Remission, Spontaneous; Research Design; Time Factors; Transplantation, Autologous

Topics: Adolescent; Adult; Amputation, Surgical; Antineoplastic Agents; Bone Neoplasms; Cell Division; Child; Clinical Trials as Topic; Doxorubicin; Drug Therapy, Combination; Female; Humans; Leucovorin; Lung Neoplasms; Male; Methotrexate; Neoplasm Metastasis; Osteosarcoma; Prognosis; Radiotherapy, High-Energy; Time Factors

Body weight loss is frequently regarded as negatively related to outcomes in patients with malignancies. This retrospective analysis of the FIRE-3 study evaluated the evolution of body weight in patients with metastatic colorectal cancer (mCRC). FIRE-3 evaluated first-line FOLFIRI (folinic acid, fluorouracil and irinotecan) plus cetuximab or bevacizumab in mCRC patients with RAS-WT tumors (ie, wild-type in KRAS and NRAS exons 2-4). The prognostic and predictive relevance of early weight loss (EWL) regarding patient outcomes and treatment side effects were evaluated. Retrospective data on body weight during first 6 months of treatment were evaluated (N = 326). To correlate with efficacy endpoints and treatment side effects, patients were grouped according to clinically significant EWL ≥5% and <5% at Month 3. Age constituted the only significant predictor of EWL following a linear relationship with the corresponding log odds ratio (P = .016). EWL was significantly associated with the incident frequencies of diarrhea, edema, fatigue, nausea and vomiting. Further, a multivariate analysis revealed EWL to be an independent negative prognostic factor for overall survival (32.4 vs 21.1 months; hazard ratio [HR]: 1.64; 95% confidence interval [CI] = 1.13-2.38; P = .0098) and progression-free survival (11.8 vs 9.0 months; HR: 1.72; 95% CI = 1.18-2.5; P = .0048). In conclusion, EWL during systemic treatment against mCRC is significantly associated with patient age. Patients exhibiting EWL had worse survival and higher frequencies of adverse events. Early preventative measures targeted at weight maintenance should be evaluated, especially in elderly patients being at highest risk of EWL.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Cetuximab; Colorectal Neoplasms; Female; Fluorouracil; Follow-Up Studies; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Prognosis; Prospective Studies; Retrospective Studies; Risk Factors; Survival Rate; Weight Loss

Clinicopathologic characteristics and prognostic and predictive factors offer valuable guidance when selecting optimal first-line treatment in patients with metastatic colorectal cancer (CRC). The association between baseline circulating tumor cell (bCTC) count, molecular tumor profile, and clinicopathologic features was analyzed in a chemo-naïve metastatic CRC population.. A total of 1202 patients from the Spanish VISNÚ-1 (FOLFIRINOX/bevacizumab vs. FOLFOX/bevacizumab) and VISNÚ-2 (FOLFIRI/bevacizumab vs. FOLFIRI/cetuximab; RAS-wildtype) studies were analyzed for mutational status and bCTC count. The association between clinicopathologic characteristics and bCTC count, mutational status, and microsatellite instability (MSI) was analyzed in 589 eligible patients.. Interestingly, 41% of the population studied presented ≥3 bCTC count. bCTC count ≥3 was associated with worse performance status (according Eastern Cooperative Oncology Group scale), stage IV at diagnosis, at least 3 metastatic sites, and elevated carcinoembryonic antigen (CEA) levels; but not with RAS or BRAF mutations or high MSI. BRAFmut (BRAF mutated) tumors were associated with right-sided primary tumors, peritoneum, distant lymph node metastasis, and less frequent liver involvement. RASmut (RAS mutated) was associated with worse performance status; stage IV at diagnosis; right-sided primary tumors; liver, lung, and bone metastases; at least 3 metastatic sites; and elevated CEA, whereas PIK3CAmut (PIK3CA mutated) tumors were associated with right-sided primary tumors, high CEA serum levels, and older age. High MSI was associated with right-sided primary tumors, distant lymph nodes metastasis, and lower CEA levels.. In our study, elevated bCTCs and RASmut were associated with clinicopathologic features known to be associated with poor prognosis; whereas the poor prognosis of BRAFmut tumors in chemo-naïve metastatic CRC is not explained by associations with poor clinicopathologic prognostic factors, except right-sided primary tumors.. VISNU 1 ClinicalTrials.gov ID: NCT01640405/ VISNU 2 ClinicalTrials.gov ID: NCT01640444.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Biomarkers, Tumor; Bone Neoplasms; Camptothecin; Cell Count; Colorectal Neoplasms; DNA Mutational Analysis; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Microsatellite Instability; Middle Aged; Mutation; Neoplasm Staging; Neoplastic Cells, Circulating; Organoplatinum Compounds; Oxaliplatin; Prognosis; Progression-Free Survival; Prospective Studies; Proto-Oncogene Proteins B-raf; ras Proteins; Risk Assessment; Young Adult

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

The purpose of this work is to assess the heterogeneity across organs of response to treatment in metastatic colorectal patient based on longitudinal individual target lesion diameters (ILD) in comparison to sum of tumor lesion diameters (SLD). Data were from the McCAVE trial, in which 189 previously untreated patients with metastatic colorectal carcinoma (mCRC) received either bevacizumab (control, C) or vanucizumab (experimental, E), on top of standard chemotherapy. Bayesian hierarchical longitudinal non-linear mixed effect models were fitted to the data using Hamilton Monte Carlo algorithm to characterize the time dynamics of the tumor burden, and to obtain estimates of the tumor shrinkage and regrowth rates. The ILD model brought more nuanced results than to the SLD model. Besides substantial differences in tumor size at baseline (with lesions located in liver more than twice as large as the ones in lungs), it revealed a more durable response in lesions located in lymph nodes and 'other organs' compared to liver and lungs. Specifically, in lymph nodes and 'other organs', the projected time to nadir was doubled in group E (2.12 and 2.44 years respectively) compared to group C (1.07 and 1.20 years respectively). This long period of tumor shrinkage associated with a slightly larger change from baseline at nadir (- 51.4% in lymph nodes and - 62.6% in 'other organs' in the group E, compared to - 46.2% and - 46.9% in group C) resulted in a clinically meaningful difference in the tumor dynamics of patients in group E compared to the group C. The proportion of variance explained by the inter-lesion variability for each model parameter was large (ranging between 10 and 56%), reflecting the heterogeneity in tumor dynamics across organs. These findings suggest that there is value in understanding both within- and between-patient variability in tumor size's time dynamics using an appropriate modeling framework, as this information may help in pairing the right treatment with individual patient profile.

Topics: Adult; Aged; Aged, 80 and over; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bayes Theorem; Bevacizumab; Biological Variation, Individual; Biological Variation, Population; Colorectal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Liver; Liver Neoplasms; Longitudinal Studies; Lung; Lung Neoplasms; Lymph Nodes; Male; Middle Aged; Models, Biological; Monte Carlo Method; Organoplatinum Compounds; Tumor Burden

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

Akt activation is common in gastric/gastroesophageal junction cancer (GC/GEJC) and is associated with chemotherapy resistance. Treatment with ipatasertib, a pan-Akt inhibitor, may potentiate the efficacy of chemotherapy in GC/GEJC.. In this randomised, double-blind, placebo-controlled, multicentre, phase II trial, patients with locally advanced or metastatic GC/GEJC not amenable to curative therapy were randomised 1:1 to receive ipatasertib or placebo, plus mFOLFOX6 (modified regimen of leucovorin, bolus and infusional 5-fluorouracil [5-FU], and oxaliplatin). The co-primary end-point was progression-free survival (PFS) in the intent-to-treat (ITT) population and in phosphatase and tensin homolog (PTEN)-low patients. Secondary end-points included PFS in patients with PI3K/Akt pathway-activated tumours; overall survival, investigator-assessed objective response rate and duration of response in the ITT population; and safety assessments.. In 153 enrolled patients, the median PFS (ITT) was 6.6 months (90% confidence interval [CI], 5.7-7.5) with ipatasertib/mFOLFOX6 versus 7.5 months (90% CI, 6.2-8.1) with placebo/mFOLFOX6 (hazard ratio, 1.12; 90% CI, 0.81-1.55; P = 0.56). No statistically significant PFS benefit was observed in biomarker-selected patient subgroups (PTEN-low and PI3K/Akt pathway-activated tumours) with ipatasertib/mFOLFOX6 versus placebo/mFOLFOX6. Other secondary end-points did not favour the ipatasertib/mFOLFOX6 treatment arm. The percentages of patients with ≥1 adverse event (AE, 100% versus 98%) and grade ≥3 AEs (79% versus 74%) were similar between arms. Higher rates of AEs leading to treatment withdrawal (16% versus 6%) and serious AEs were reported in the ipatasertib arm (54% versus 43%). Thirty-nine and 29 deaths occurred in the ipatasertib and placebo arms, respectively.. Ipatasertib/mFOLFOX6 compared with placebo/mFOLFOX6 did not improve PFS in unselected or biomarker-selected patients. No unexpected safety concerns were observed.. ClinicalTrials.gov (NCT01896531).

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Carcinoma; Esophagogastric Junction; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymph Nodes; Male; Middle Aged; Organoplatinum Compounds; Piperazines; Progression-Free Survival; Proto-Oncogene Proteins c-akt; Pyrimidines; Stomach Neoplasms

Liposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin (5-FU/LV) is approved for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy. This approval was based on significantly improved median overall survival compared with 5-FU/LV alone (6.1 vs 4.2 months; hazard ratio [HR], 0.67) in the global phase 3 NAPOLI-1 trial. Here, we report the final survival analysis and baseline characteristics associated with long-term survivors (survival of ≥1 year) in the NAPOLI-1 trial.. Patients with mPDAC were randomised to receive nal-IRI + 5-FU/LV (n = 117), nal-IRI (n = 151), or 5-FU/LV (n = 149) for the first 4 weeks of 6-week cycles. Baseline characteristics and efficacy in the overall population were compared with those in patients who survived ≥1 year. Through 16th November 2015, 382 overall survival events had occurred.. The overall survival advantage for nal-IRI+5-FU/LV vs 5-FU/LV was maintained from the original nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1) analysis (6.2 vs 4.2 months, respectively; HR, 0.75; 95% confidence interval: 0.57-0.99). Median progression-free survival, objective response rate and disease control rate also favoured nal-IRI+5-FU/LV therapy. Estimated one-year overall survival rates were 26% with nal-IRI+5-FU/LV and 16% with 5-FU/LV. Baseline characteristics associated with long-term survival in the nal-IRI+5-FU/LV arm were Karnofsky performance status ≥90, age ≤65 years, lower CA19-9 levels, neutrophil-to-lymphocyte ratio ≤5 and no liver metastases. No new safety concerns were detected.. The survival benefits of nal-IRI+5-FU/LV versus 5-FU/LV were maintained over an extended follow-up, and prognostic markers of survival ≥1 year were identified.. NCT01494506.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; CA-19-9 Antigen; Carcinoma, Pancreatic Ductal; Female; Fluorouracil; Humans; Irinotecan; Karnofsky Performance Status; Leucovorin; Liposomes; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Pancreatic Neoplasms; Progression-Free Survival; Proportional Hazards Models

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

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

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

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

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

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

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

This is a multicenter phase II study to assess the efficacy and toxicity of FOLFIRI treatment agents in full and the influence of UGT1A1*28 polymorphism in Japanese patients with advanced/metastatic colorectal cancer (mCRC).. Fifty patients with mCRC participated in this study. Treatment consisted of FOLFIRI (irinotecan; 150 mg/m(2)) as second-line chemotherapy; 34 patients consented to the evaluation of UGT1A1 genotype.. The overall response rate was 12% for all 50 evaluable patients; 31 patients (62.0%) had stable disease, and only in 12 (24.0%) did disease progress. The median progression-free survival was 5.8 months. The tolerance treatment was acceptable, with only 15 out of 50 patients (30%) experiencing grade 3/4 neutropenia, and grade 4 thrombocytopenia was observed in only one case. Grade 3 non-hematological adverse reactions included stomatitis in three, diarrhea in one, and a clinically insignificant increase in serum alkaline phosphatases in one patient, respectively. There was no definite relation between the UGT1A1*28 polymorphism and toxicity.. Standard FOLFIRI regimen can be administered to Japanese patients. The results showed good tolerability and efficacy for second-line FOLFIRI, provided that evaluation of UGT1A1 polymorphism is properly implemented before the start of the chemotherapy.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Female; Fluorouracil; Follow-Up Studies; Glucuronosyltransferase; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Polymorphism, Genetic; Prognosis; Promoter Regions, Genetic; 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

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

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

Despite median survival of less than 6 months, there is a significant proportion of advanced pancreatic cancer patients who progress on gemcitabine that remains fit, and these patients are candidates for second-line treatment.. The objective of this study is to evaluate the efficacy and safety of oxaliplatin plus 5-fluorouracil and folinic acid in patients with gemcitabine-pretreated advanced pancreatic cancer.. Thirty patients with advanced pancreatic cancer who were pretreated with gemcitabine received oxaliplatin (85 mg/m(2)) on days 1 and 15 followed by leucovorin (20 mg/m(2)) and 5-fluorouracil (500 mg/m(2)) on days 1, 8, and 15. The cycle was repeated every 3 weeks.. The majority of patients (80 %) had locally advanced disease. Median age was 63 years, and 60 % were males. The liver was the most common site of metastasis. Partial response was observed in 2 patients (6.7 %) and stable disease in 6 patients (20 %), while 12 patients progressed (40 %). Improved performance status was reported in 10 patients (33.3 %). The median duration of response was 13 weeks, and median overall survival was 22 weeks. There was no grade 4 toxicity apart from grade 4 neutropenia in 6.6 % of patients. Neutropenia (46.5 %) and neuropathy (43.2 %) were the most common toxicities, while hand-foot syndrome was the least frequent one (20 %). There were no treatment-related deaths. The 6-month survival rate was 30 %.. This regimen is feasible and active with an acceptable toxicity; however, further investigation in phase III trial is needed.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Deoxycytidine; Female; Fluorouracil; Follow-Up Studies; Gemcitabine; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Pancreatic Neoplasms; Prognosis; Survival Rate

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

The aim of this phase II study was to investigate the efficacy and safety of oxaliplatin plus 5-fluorouracil (5-FU) and leucovorin (LV) in metastatic breast cancer (MBC) patients heavily pretreated with anthracyclines, taxanes, vinorelbine, gemcitabine, and capecitabine. Sixty-two women who had received at least 3 above-mentioned drug classes were treated with oxaliplatin 85 mg/m(2) as a 2-h infusion on day 1, LV 200 mg/m(2) as a 2-h infusion followed by bolus 5-FU 400 mg/m(2) on day 1, and a continuous infusion of 5-FU 1,200 mg/m(2) for 44 h. The median patient age was 52 years with a median of two involved organs, and the metastases were mostly in the lung (53.2%), lymph nodes (51.6%), and liver (45.2%). Patients had a median of three prior chemotherapy regimens. Forty-five patients (72.6%) had prior exposure to all 5 classes of drugs. Based on an intention-to-treat analysis, 60 patients were assessable for responses and 11 patients achieved a partial response (PR), giving an overall response rate (ORR) of 18.3%. Twenty-one (35%) patients had stable disease (SD), and of these, 8 achieved long SD (13.3%). The median progression-free survival (PFS) was 3 months, and the median overall survival (OS) was 10 months. Toxicity was mild to moderate with grade 3 or 4 neutropenia, thrombocytopenia, and neuropathy occurring in 14 (22.6%), 9 (14.5%), and 3 (4.8%) patients, respectively. The study demonstrated that the combination of oxaliplatin plus 5-FU/LV was a well-tolerated salvage regimen with moderate activity in patients with heavily pretreated MBC.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Prognosis; Salvage Therapy; Survival Rate; Young Adult

To determine whether the change in tumor diameters at the first follow-up computed tomography (CT) examination after baseline examination (first change) correlates with outcome in patients with metastatic colorectal cancer (mCRC) treated with combination chemotherapy.. The first change was analyzed in a multicenter randomized phase III trial (Nordic VI, N = 567) comparing first-line irinotecan with either bolus or infused 5-fluorouracil. Cox proportional hazards multiple regression model and Kaplan-Meier survival analyses after correction for guarantee-time bias were carried out to evaluate correlations between first change, objective response according to RECIST 1.0, progression-free survival (PFS), and overall survival (OS).. The hazard ratios for PFS and OS decreased along with first change. A decrease between 10% and <30%, albeit RECIST does not regard this as a partial response, was a positive prognostic factor for PFS and OS. Patients who had new lesions or unequivocal progression of nonmeasurable lesions had a worse prognosis than those with only an increase in size of >20%.. The change in tumor size at the first follow-up CT is strongly prognostic for PFS and OS in mCRC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Disease-Free Survival; Female; Fluorouracil; Humans; Irinotecan; Kaplan-Meier Estimate; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Proportional Hazards Models; Treatment Outcome; Tumor Burden

We investigated the efficacy and safety of oral Uracil/tegafur (UFT) with leucovorin and mitomycin C (MMC) as third-line treatment for patients with extensively pretreated metastatic colorectal cancer (mCRC). This was a multicenter, prospective phase II study. Patients received MMC 7 mg/m² on day 1 and UFT 300 mg/m² with leucovorin 90 mg, both divided into three daily doses, on days 1-28 every 5 weeks. All patients had failed prior treatment with irinotecan, oxaliplatin, fluoropyrimidine, bevacizumab, and cetuximab. The primary endpoint was tumor control rate evaluated after 2 cycles. Twenty-one patients were included: median age was 66 years (41.1-87.8 years). Tumor control rate was observed in 26.7% of the 15 patients evaluable for response. Median overall survival was 6.4 months. Grade 3 adverse events were asthenia, anorexia, and vomiting. In patients with mCRC who have progressed after as many as two prior therapies, the combination of UFT/leucovorin and MMC is safe and may produce a short stabilization of disease in approximately 25% of patients.

Topics: Adult; Aged; Aged, 80 and over; Anorexia; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Asthenia; Colorectal Neoplasms; Drug Combinations; Drug Monitoring; Female; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Mitomycin; Neoplasm Grading; Salvage Therapy; Survival Analysis; Tegafur; Tumor Burden; Uracil

To examine FOLFOX/bevacizumab/cetuximab in the first-line treatment of metastatic colorectal cancer (mCRC).. Randomized phase II trial aimed at achieving a 60% objective response rate (ORR). Due to frequent cetuximab-related hypersensitivity reactions the trial was amended to a single-arm design. Eligibility: Previously untreated mCRC, measurable disease, Eastern Cooperative Oncology Group performance status (ECOG-PS) 0-1.. Modified FOLFOX6 (oxaliplatin 85 mg/m², leucovorin 350 mg, and 5-fluorouracil 400 mg/m² bolus; 2.4 g/m² infusion, 46 h) day 1; bevacizumab 5 mg/kg on day 1; cetuximab 400 mg/m² on day 1, then 250 mg/m² on days 1 and 8, every 14 days (1 cycle) until progressive disease (PD); restaging occurred every 4 cycles.. With emerging negative progression-free survival (PFS) data from a similarly designed trial, this trial closed early. Enrollment (N=31) was from August 2005-June 2008.. Median age was 55 years (29-78); 58% were male; 71% were ECOG-PS 0. Ten cycles (median) were completed (range 2-62). The ORR was 55% (95% confidence interval [CI], 36-73%); 11 patients (35%) had stable disease; 1 patient (3%) had PD; 2 patients (6%) were unevaluable. Median PFS was 9 months (95% CI, 8.3-15.2 months); median overall survival was 25.7 months (95% CI, 15.4-27.6 months). Grade 3/4 toxicities (>1 patient) included neutropenia (25%), rash (23%; grade 2 events, 45%), diarrhea (19%), fatigue (16%), pain (16%), anemia (13%), sensory neuropathy (13%), deep-vein thrombosis (10%), nausea (10%), pulmonary embolism (7%), anorexia (6%), and vomiting (6%).. In this limited trial, it is unclear whether cetuximab contributed to FOLFOX/bevacizumab efficacy, although the response rate, PFS, and overall survival were high. The regimen was generally well-tolerated, with expected skin effects; thromboembolic rates should be assessed in larger analyses. Cetuximab's role in first-line mCRC treatment is likely best guided by K-RAS testing in future clinical trials.

Topics: Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Cetuximab; Colorectal Neoplasms; Disease Progression; Drug Therapy, Combination; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Organoplatinum Compounds; Treatment Outcome

FOLFOX-4 and FOLFIRI are considered equivalent in terms of activity and efficacy as first-line chemotherapy in metastatic colorectal cancer (mCRC). The monoclonal antibody (mAb) cetuximab showed intrinsic activity as a single agent in mCRC and was approved in combination with CPT-11 for patients who failed previous CPT-11-based treatment. The purpose of this phase II study was to evaluate the activity and safety of FOLFOX-4 plus cetuximab in untreated mCRC patients.. Untreated patients with measurable metastatic disease and expressing epidermal growth factor receptor (EGFR) received cetuximab at a loading dose of 400 mg/m(2), followed by weekly doses of 250 mg/m(2), in combination with the FOLFOX-4 regimen every 2 weeks for a maximum of 12 cycles, after which a maintenance program using cetuximab alone was allowed for a maximum of 6 months.. Eighty-two unselected patients were screened; 70 were EGFR+ and entered the trial. Of the 67 assessable patients, the objective response rate was 64.2% (95% CI: 52.5-75.5%) and the tumor growth control rate was 94% (95% CI: 88-99%). All the objective responses except 1 were confirmed. In the group of patients with initially unresectable liver disease alone, 7/33 (21%) were resected. The median time to progression (TTP) and overall survival (OS) were 10.0 and 22.0 months, respectively. The treatment was well tolerated, with no treatment-related deaths, while 24.2% of the patients were affected by cutaneous toxicity of grade >2. Mutational analysis of the KRAS and BRAF genes was retrospectively performed on 35 of the 69 patients treated with cetuximab (51%). KRAS was mutated in 13 out of the 35 cases (37%), whereas no mutations were detected in the BRAF gene. A trend toward an association between KRAS mutations and objective response to treatment (p = 0.07) was demonstrated. Analysis of survival showed that patients harboring KRAS mutations had a trend toward worst TTP (p = 0.14) confirmed by age- and sex-adjusted Cox multivariate regression (hazard ratio, HR = 0.62; 95% CI: 0.36-1.06; p = 0.08). Indeed, KRAS mutations were significantly associated with worst OS in both unadjusted analysis (p = 0.047; log rank test) and age- and sex-adjusted Cox multivariate regression (HR = 0.458; 95% CI: 0.248-0.847; p = 0.01).. These results suggest that the combination of FOLFOX-4 plus cetuximab is very active and obtains long TTP with an acceptable toxicity profile. Indeed, our results are in line with recent findings from phase II and phase III randomized studies providing strong evidence that the efficacy of anti-EGFR mAb is confined to patients with wild-type KRAS mCRC. Investigation of other predictive biomarkers may be useful to further define the responder population.

Topics: Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Cetuximab; Colorectal Neoplasms; ErbB Receptors; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Mutation; Organoplatinum Compounds; Proto-Oncogene Proteins; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras); ras Proteins

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

FOLFIRI is one of the current standard first-line regimens for advanced colorectal cancer, but its administration is onerous. Because the replacement of 2-day-infusional 5-fluorouracil (5-FU) of FOLFIRI with oral tegafur-uracil/leucovorin (UFT/LV) would be highly beneficial for clinical management, we performed a phase I trial using oral UFT/LV and a pharmacokinetic evaluation.. Treatment consisted of infusional irinotecan (100 mg/m)/l-LV (15 mg/m) and a bolus injection of 5-FU (500 mg/m) on day 1, and oral UFT (300 mg as tegafur/m/d)/LV (75 mg/d) on days 1-5 (level 1), days 1-7 (level 2), or days 1-10 (level 3). Cycles were repeated every 14 days. After determination of the recommended UFT/LV administration period, irinotecan was dose-escalated (level 4: 125 mg/m; level 5: 150 mg/m).. Nineteen patients were enrolled. One dose-limiting toxicity (DLT), grade 4 neutropenia lasting for > or =4 days was observed at level 2. At level 3, one DLT of treatment delay of > or =8 days occurred due to prolonged neutropenia, and 2 patients refused to continue the treatment because of prolonged grade 2 anorexia. Therefore, a 7-day administration of UFT/LV was recommended. No DLT was observed at levels 4 and 5. Pharmacokinetic evaluation suggested continuous exposure to 5-FU by means of oral UFT/LV administration in this combination.. The recommended administration period was 7 days for oral UFT/LV, and the recommended dose of irinotecan was 150 mg/m. A phase II study is ongoing to validate the clinical outcome.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Camptothecin; Colorectal Neoplasms; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Maximum Tolerated Dose; Middle Aged; Prognosis; Survival Rate; Tegafur; Tissue Distribution; 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

Oral treatment regimens with few side effects are appealing in the 2nd or 3rd line treatment of non-small cell lung cancer (NSCLC) patients.. The aim was to investigate the efficacy and toxicity of the oral combination etoposide, Uracil-Tegafur (UFT) and leucovorin in 2nd or 3rd line in Caucasian patients with advanced NSCLC.. Etoposide 50 mg/m(2), UFT 250 mg/m(2) and leucovorin 90 mg (fixed dose) were dosed in 3 gifts approximately 8h apart for 14 days followed by 1 week rest every 3 weeks until progressive disease (PD). Primary endpoint was response rate (RR), secondary endpoints toxicity and time to progression (TTP).. The median number of cycles was 3.5 (95% CI 2-5); 9 patients received > or =6 cycles, 4>10 cycles. The median dose intensities for etoposide and UFT were 223 mg/m(2)/week (95% CI 213-232) and 1092 mg/m(2)/week (95% CI 1032-1167), the relative dose intensities 92% and 90%, respectively. Grade 3/4 neutropenia was observed in 12% (4/32), grade 3/4 thrombocytopenia in 15% (5/32), without febrile neutropenia. Non-hematological toxicity grade 3 included hepatic toxicity (6%), lethargy (15%), diarrhea (3%) and nausea (3%). One patient developed grade 4 arterial ischemia. Fourteen percent (95% CI 4-33%) (4/28) had a confirmed partial response, 57% (95% CI 44-81%) (16/28) stable disease and 28% (95% CI 19-56%) (8/28) progressive disease. The median TTP was 3 months (95% CI 1.3-4.4), the median overall survival 6.7 months (95% CI 4.0-9.3).. The combination of UFT, etoposide and leucovorin is active in 2nd or 3rd line therapy of Caucasian NSCLC patients and because of its favourable toxicity profile this treatment warrants further investigation.

Topics: Administration, Oral; Alopecia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Etoposide; Female; Humans; Kaplan-Meier Estimate; Leucovorin; Lung Neoplasms; Male; Neoplasm Recurrence, Local; Neoplasm Staging; Neutropenia; Tegafur; Uracil

This study is to compare the remission and complication rates of actinomycin D (Act-D) and methotrexate-folinic acid (MTX-FA) as single-agent treatments of stage I, low-risk gestational trophoblastic neoplasia (GTN). From 1994 to 2005, all women with International Federation of Gynecology and Obstetrics stage I, low-risk GTN were randomly assigned to received either intravenous Act-D 10 microg/kg per day for 5 days every 2 weeks or intramuscular methotrexate 1 mg/kg per day on days 1, 3, 5, and 7 with intramuscular folinic acid 0.1 mg/kg per day on days 2, 4, 6, and 8 every 2 weeks. Forty-nine women met the eligibility criteria. Age, human chorionic gonadotropin level, and International Federation of Gynecology and Obstetrics score were similar in both treatment groups. Of the 22 women who received Act-D, 2 were lost to follow-up. Among the 27 women who received MTX-FA, 2 were lost to follow-up, and 6 had to switch to Act-D because of the rising levels of liver enzymes. All 20 women (100%) in the Act-D arm achieved remission compared with 14 (73.6%) in 19 women in the MTX-FA arm (P = 0.02). Mucositis and alopecia were reported more frequently in the Act-D group, whereas elevations of liver enzyme levels were more frequent in the MTX-FA group. Actinomycin D seems to be more effective than MTX-FA in the treatment of stage I, low-risk GTN. Larger multicenter randomized controlled trials should be conducted to establish the most appropriate regimen for these patients.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Dactinomycin; Female; Gestational Trophoblastic Disease; Humans; Leucovorin; Lung Neoplasms; Maximum Tolerated Dose; Methotrexate; Neoplasm Staging; Pregnancy; Prognosis; Survival Rate; Treatment Outcome; Vitamin B Complex

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

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

Adjuvant systemic chemotherapy administered after surgical resection of colorectal cancer metastases may reduce the risk of recurrence and improve survival, but its benefit has never been demonstrated. Two phase III trials (Fédération Francophone de Cancérologie Digestive [FFCD] Trial 9002 and the European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada Clinical Trials Group/Gruppo Italiano di Valutazione Interventi in Oncologia [ENG] trial) used a similar design and showed a trend favoring adjuvant chemotherapy, but both had to close prematurely because of slow accrual, thus lacking the statistical power to demonstrate the predefined difference in survival. We report here a pooled analysis based on individual data from these two trials.. After complete resection of colorectal liver or lung metastases, patients were randomly assigned to chemotherapy (CT arm; fluorouracil [FU] 400 mg/m(2) administered intravenously [IV] once daily plus dl-leucovorin 200 mg/m(2) [FFCD] x 5 days or FU 370 mg/m(2) plus l-leucovorin 100 mg/m(2) IV x 5 days [ENG] for six cycles at 28-day intervals) or to surgery alone (S arm).. A total of 278 patients (CT, n = 138; S, n = 140) were included in the pooled analysis. Median progression-free survival was 27.9 months in the CT arm as compared with 18.8 months in the S arm (hazard ratio = 1.32; 95% CI, 1.00 to 1.76; P = .058). Median overall survival was 62.2 months in the CT arm compared with 47.3 months in the S arm (hazard ratio = 1.32; 95% CI, 0.95 to 1.82; P = .095). Adjuvant chemotherapy was independently associated with both progression-free survival and overall survival in multivariable analysis.. This pooled analysis shows a marginal statistical significance in favor of adjuvant chemotherapy with an FU bolus-based regimen after complete resection of colorectal cancer metastases.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colorectal Neoplasms; Disease-Free Survival; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Multivariate Analysis; Neoplasm Staging; Survival Rate

To evaluate the antitumor activity and toxicity of 5-fluorouracil (FU)/leucovorin (LV) and capecitabine (C) given with either oxaliplatin (OX) or camptothecin (CPT-11) in the treatment of chemotherapy naive patients with metastatic colorectal cancer.. The outpatient treatment, consisted of 2 consecutive days of LV, 200 mg/m(2), 5-FU 400 mg/m(2), and C 2000 mg/m(2) that, in one cycle, was preceded by 2 days of OX 50 mg/m(2), and, in the subsequent cycle, by CPT-11, 90 mg/m(2).. All 54 patients were assessable for toxicity and response. Thirty-two patients responded, giving an overall response rate of 59.3%. Median progression-free survival was 12.3 months and median survival was 20.5 months. Toxicity included grade 3 to 4 neutropenia in 43% of patients, grade 3 diarrhea in 7% of patients, and grade 2 neurotoxicity in 6% of patients.. The alternating, bimonthly schedule of OX and CPT-11 plus 5-FU/LV/C has substantial antitumor activity and is well tolerated.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Brain Neoplasms; Camptothecin; Capecitabine; Colorectal Neoplasms; Deoxycytidine; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Organoplatinum Compounds; Oxaliplatin; Prognosis; Prospective Studies; Survival Rate; Treatment Outcome

To evaluate the efficacy and toxicity of a biweekly DOF regimen consisting of docetaxel, oxaliplatin, 5-fluorouracil and leucovorin for advanced gastric cancer.. The biweekly DOF regimen was administered in 37 advanced gastric cancer patients. Docetaxel, oxaliplatin and leucovorin were given intravenously at a dose of 35 mg/m2, 85 mg/m2 and 200 mg/m2 for 1 h, 2 h and 2 h on D1, respectively, and 5-Fu was administered as continuous intravenous infusion for 48 h at a dose of 1500 mg/m2 on D1 and D2. This regimen was repeated every 2 weeks. The efficacy and toxicity were evaluated after completion of 3 cycles at least.. The overall response rate (RR) of this series was 67.6%, complete response rate and partial response rate were 27.0% and 40.5%, respectively. The time to progression (TTP) was 9.2 months, and median survival time (MST) was 13.7 months. The RRs of 11 chemotherpy-naïve patients and 26 patients pre-treated with chemotherapy were 81.8% and 61.5%, respectively.. Our preliminary results showed that this biweekly combination regimen of docetaxel, oxaliplatin, 5-fluorouracil and leucovorin is effective and tolerable for advanced gastric cancer. However, further investigation of this regimen is mandatory.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Leukopenia; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Remission Induction; Stomach Neoplasms; Taxoids; Vomiting; Young Adult

Oxaliplatin stop and go in combination with leucovorin and 5-fluorouracil has been successfully used in a previous study (OPTIMOX1) in metastatic colorectal cancer (MCR). Celecoxib is an anti-cyclooxygenase-2 drug with anti-neoplastic properties. In the present study, celecoxib was evaluated in combination with FOLFOX7 regimen and as a single agent in maintenance therapy.. This phase II study examined for previously untreated MCR patients the stop-and-go procedure [six cycles of folinic acid, 5FU and oxaliplatin (FOLFOX7) followed by chemotherapy-free intervals (CFIs) and reintroduction at progression] with continuous administration of celecoxib (800 mg/day).. Forty-four patients were included, 42 eligible: performance status (%) 0/1/2=45/40/15, median age 60 (31-76) years. Response rate (RR) was 43% (95% CI 28%-58%). Median progression-free survival (PFS) was 6 months; median overall survival was 15.8 months. Grade 3/4 toxicity criteria were neurotoxicity 9.5%, thrombocytopenia 21.4%, neutropenia 7.1%, diarrhea 7.1%, nausea 4.8% and vomiting 2.4%. Median CFI 1 (n=27) duration was 3.9 months (range 2-39 months).. With an acceptable safety profile, celecoxib combined with FOLFOX7 achieved RR and PFS in the lower range of that obtained with FOLFOX7 alone. These results indicate the lack of synergy between FOLFOX7 and celecoxib. PFS of 6 months appears lower than PFS obtained in OPTIMOX1 study with simplified LV5FU2 in maintenance therapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Celecoxib; Colorectal Neoplasms; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Pyrazoles; Sulfonamides; Survival Rate; Treatment Outcome

The association between oxaliplatin and 5-fluorouracil (5-FU) has been extensively reported to improve prognosis of gastric cancer patients. The present study is aimed at evaluating response rate and the toxicity profile of the association with oxaliplatin, 5-FU/lecovorin and epirubicin in gastric cancer patients with locally advanced or metastatic disease. Thirty-six patients have been enrolled and 35 evaluated. The treatment schedule was oxaliplatin (100 mg m(-2)), 5-FU (400 mg m(-2)), leucovorin (40 mg m(-2)) and epirubicin (60 mg m(-2)) intravenously. administered every 3 weeks for 6 months, for a total of 185 therapy cycles . Response rate and toxicity were assessed according to the international WHO criteria. Every patient received a mean of 5.3 therapy cycles in a day-hospital setting. Sixteen of 35 patients (46%) showed an objective response, two complete response and 14 partial response. Median time to progression was 33 weeks with an overall median survival of 49 weeks. During the study, anaemia grade 3 and neutropenia grade 3 were observed in 9 and 11% of patients respectively. A grade 3 periferic sensorial neuropathy was observed in 6% of patients. No life threatening or cardiac toxicity was recorded. The regimen used showed anticancer activity against gastric carcinoma, a tolerable toxicity profile and excellent patient compliance.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Colorectal Neoplasms; Epirubicin; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Prognosis; Survival Rate

Colorectal cancer is the second leading cause of cancer mortality in the United States. Antiangiogenic therapy with bevacizumab combined with chemotherapy improves survival in previously untreated metastatic colorectal cancer. This study was conducted to determine the effect of bevacizumab (at 10 mg/kg) on survival duration for oxaliplatin-based chemotherapy in patients with previously treated metastatic colorectal cancer.. Eight hundred twenty-nine metastatic colorectal cancer patients previously treated with a fluoropyrimidine and irinotecan were randomly assigned to one of three treatment groups: oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) with bevacizumab; FOLFOX4 without bevacizumab; or bevacizumab alone. The primary end point was overall survival, with additional determinations of progression-free survival, response, and toxicity.. The median duration of survival for the group treated with FOLFOX4 and bevacizumab was 12.9 months compared with 10.8 months for the group treated with FOLFOX4 alone (corresponding hazard ratio for death = 0.75; P = .0011), and 10.2 months for those treated with bevacizumab alone. The median progression-free survival for the group treated with FOLFOX4 in combination with bevacizumab was 7.3 months, compared with 4.7 months for the group treated with FOLFOX4 alone (corresponding hazard ratio for progression = 0.61; P < .0001), and 2.7 months for those treated with bevacizumab alone. The corresponding overall response rates were 22.7%, 8.6%, and 3.3%, respectively (P < .0001 for FOLFOX4 with bevacizumab v FOLFOX4 comparison). Bevacizumab was associated with hypertension, bleeding, and vomiting.. The addition of bevacizumab to oxaliplatin, fluorouracil, and leucovorin improves survival duration for patients with previously treated metastatic colorectal.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colorectal Neoplasms; Disease Progression; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Maximum Tolerated Dose; Medical Oncology; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Probability; Risk Assessment; Salvage Therapy; Single-Blind Method; Survival Analysis; Treatment Outcome; United States

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

To evaluate the efficacy and the toxicity of front line FOLFOX4 combined with bevacizumab in patients with metastatsic CRC (mCRC).. Chemotherapy-naïve patients with mCRC, received bevacizumab (5 mg/kg every 2 weeks d1), oxaliplatin (85 mg/m2 on d1), leucovorin (200 mg/m2) on days 1 and 2 and 5-Fluorouracil (400 mg/m2 as i.v. bolus and 600 mg/m2 as 22 h i.v. continuous infusion on days 1 and 2) every 2 weeks.. Fifty three patients (46 with a PS 0-1) were enrolled. Complete and partial response was achieved in eight (15.1%) and 28 (52.8%) patients, respectively (ORR: 67.9%; 95% C.I.: 53.8%-92%); 11 (20.7%) patients had stable disease and six (11.3%) progressive disease. With a median follow up period of 13.5 months, time to tumor progression was 11 months while the median survival has not yet been reached; the probability of 1-, 2- and 3- year survival was 79.8%, 63.8% and 58.3%, respectively; Two patients relapsed during the follow up period. Eight (15%) patients underwent metastasectomy with R0 resections. Grade 3-4 neutropenia occurred in 15.1% of patients and one (1.9%) of them presented febrile neutropenia. Non-hematologic toxicity included grade 3 diarrhea (7.6%) and grade 2 and 3 neurotoxicity in 16.9 and 15.1% of patients, respectively. One (1.9%) patient presented pulmonary embolism and one (1.9%) cardiac ischaemia. There was one (1.9%) sudden death after the first cycle.. The combination of FOLFOX4/bevacizumab appears to be highly effective, well tolerated and merits further evaluation in patients with mCRC.

Topics: Adolescent; Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Carcinoma; Colorectal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Patient Compliance; Treatment Outcome

Conventional systemic chemotherapy for metastatic urothelial carcinoma (UC) such as methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) or cisplatin, methotrexate, and vinblastine (CMV) is associated with significant dose-limiting toxicities and even treatment-related death. The authors developed a regimen that was designed to maintain efficacy, while reducing toxicities.. Between January 1998 and July 2003, 35 patients (median age, 71 yrs) with metastatic UC were treated with 4-week cycles of P-HDFL (cisplatin 35 mg/m(2), high-dose 5-fluorouracil [5-FU] 2,600 mg/m(2), and leucovorin 300 mg/m(2), on Days 1 and 8, all given by 24-hr infusion). On Day 15, only HDFL was given again.. Among the 32 patients treated with > or = 2 cycles, 9 (28.1%) and 11 (34.4%) were complete and partial responders, respectively, with an overall response rate of 62.5% (95% confidence interval [CI], 45.9-79.2%). The median overall and progression-free survival was 12.3 months (95% CI, 8.2-16.4 mos) and 10.5 months (95% CI, 8.4-12.6 mos), respectively. Toxicity in a total of 121 courses (mean, 3.5 per patient) was modest, with WHO Grade 3 or 4 leukopenia and thrombocytopenia noted in only 1 and 0 patients, respectively. Grade 3 or 4 nausea, vomiting, mucositis, and diarrhea were noted in 3, 2, 0, and 2 patients, respectively. In general, patients tolerated the regimen very well.. P-HDFL is a moderately active and considerably low-toxic regimen for metastatic UC. The excellent toxicity profile makes it a viable option for patients with poor general conditions. To reach any conclusion, randomized trials comparing P-HDFL with traditional cisplatin-based regimens are necessary.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cisplatin; Disease-Free Survival; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Survival Rate; Treatment Outcome; Urinary Bladder Neoplasms

Only a few drugs are active in the treatment of well-differentiated endocrine carcinomas (WDEC). We evaluated the combination of the so-called 'de Gramont schedule' and irinotecan in these tumors in a phase II study.. 20 patients were enrolled in the study. The combination regimen included irinotecan, 180 mg/m(2) on day 1, followed by 200 mg/m(2) folinic acid in a 2-hour infusion, an intravenous 10-min bolus of 400 mg/m(2) 5-fluorouracil (5FU) and finally 600 mg/m(2) 5FU in a 22-hour infusion. Folinic acid and 5FU were repeated on day 2. Clinical, biological and morphological parameters were assessed by CT every 8 weeks. The site of the primary tumor was the pancreas in 10 cases, the lung in 3 cases and other sites in 7 cases. Sixteen patients had previously received chemotherapy, and 6 of them had had two lines of treatment. Six patients had previously been treated with chemoembolization.. The median number of cycles administered was 8. Grade 3-4 neutropenia was observed in 8 patients, and 1 patient experienced febrile neutropenia. There was no toxicity-related death. No complete symptomatic response was observed in 7 evaluable patients; 4 patients had an objective biological response. One patient achieved a morphological objective response, stabilization was observed in 15, but progression occurred in 3 patients. Median survival was 15 months.. The above-mentioned combination of LV5FU2 + irinotecan does not yield major activity in heavily pretreated unresectable metastatic gastroenteropancreatic WDEC, and significant toxicity was observed.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma; Drug Administration Schedule; Enteroendocrine Cells; Female; Fluorouracil; Gastrointestinal Neoplasms; Humans; Infusions, Intravenous; Irinotecan; Leucovorin; Lung Neoplasms; Male; Middle Aged; Pancreatic Neoplasms; Prospective Studies; Survival Analysis; Treatment Failure; Treatment Outcome

Aphase 1 study of gefitinib in combination with oxaliplatin, 5-fluorouracil and leucovorin (IFOX)was conducted to evaluate the safety and feasibility of this regimen.. Patients with advanced solid malignancies were treated with escalating doses of gefitinib (250 mg or 500 mg once daily) in combination with FOLFOX (oxaliplatin, 5-fluorouracil, and leucovorin). The initial dose of oxaliplatin was 70 mg/m2 with sequential dose escalation to 85 mg/m2.. Sixteen patients received a total of 138 14-day courses of daily gefitinib in combination with FOLFOX. Escalation of gefitinib from 250 mg/d to 500 mg/d with FOLFOX was well-tolerated. In addition, no severe toxicities precluded subsequent dose escalation of oxaliplatin from 70 mg/m2 to 85 mg/m2 at which no dose-limiting toxicity was seen. No further dose escalation was performed as this represented the oxaliplatin dose administered in the standard FOLFOX-4 regimen. The most predominant toxicity was diarrhea, which was well controlled with oral antidiarrheal agents. Four partial remissions occurred in patients with metastatic colorectal cancer.. Gefitinib as a 500 mg daily continuous dose was well tolerated in combination with full doses of FOLFOX-4.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms; Dose-Response Relationship, Drug; Female; Fluorouracil; Gefitinib; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Quinazolines

This phase I study was performed to evaluate the safety, tolerability, and efficacy of the oral matrix metalloproteinase inhibitor BAY 12-9566 in combination with 5-fluorouracil/leucovorin in patients with advanced solid tumours, and to identify the maximum tolerated dose and the dose for use in future studies.. BAY 12-9566 and 5-fluorouracil/leucovorin were administered to 17 patients in 3 cohorts. Each patient served as his/her own control, with 5-fluorouracil being given alone on days 1-5 of cycle 1. In cohort 1, BAY 12-9566 at 800 mg p.o. b.i.d. was given with 350 mg/m2 5-fluorouracil/20 mg/m2 leucovorin x 5 days q28 days. In cohort 2, the BAY 12-9566 dose was reduced to 400 mg p.o. b.i.d., with the 5-fluorouracil/leucovorin doses remaining unchanged. Finally, in cohort 3, BAY 12-9566 400 mg bid was given with 5-fluorouracil 400 mg/m2/day. Patients were continued on therapy until unacceptable toxicity or tumour progression occurred. Pharmacokinetic analyses for both BAY 12-9566 and 5-fluorouracil were performed.. The maximum tolerated dose was 400 mg p.o. b.i.d. BAY 12-9566 plus 5-fluorouracil/leucovorin at 400 mg/m2/day and 20 mg/m2/day, respectively. Thrombocytopenia necessitated a decrease of the dose of BAY 12-9566 by 50% from cohort 1 to cohort 2. Two dose-limiting toxicities occurred in cohort 3 consisting of neutropenic fever, and ileitis, causing severe diarrhea. Of 17 patients treated on study, 7 of 14 patients evaluable for response achieved stable disease. Pharmacokinetic analysis suggested there was no interaction between BAY 12-9566 and 5-fluorouracil.. BAY 12-9566 400 mg bid and 5-fluorouracil 350 mg/m2 plus leucovorin 20 mg/m2 can be co-administered. Although there is some evidence of a clinical interaction, there is no apparent pharmacokinetic interaction. Future studies with these 2 types of agents administered in combination are warranted.

Topics: Angiogenesis Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Biphenyl Compounds; Canada; Cohort Studies; Colorectal Neoplasms; Dose-Response Relationship, Drug; Female; Fluorouracil; Humans; Kidney Neoplasms; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Matrix Metalloproteinase Inhibitors; Maximum Tolerated Dose; Organic Chemicals; Phenylbutyrates; Safety; Salvage Therapy

Fluorouracil (5-FU), oxaliplatin and irinotecan combinations improve time to tumor progression (TTP), objective response and overall survival (OS) in patients with metastatic colorectal cancer (MCRC). Here we identify and describe patients treated on Intergroup study N9741 who initially had inoperable MCRC, but who obtained sufficient chemotherapeutic benefit to allow removal of their metastatic disease.. Patient research records in study arms (A) irinotecan/5-FU/leucovorin (LV) (IFL, n = 264), (F) oxaliplatin/5-FU/LV (FOLFOX4, n = 267) and (G) oxaliplatin/irinotecan (IROX, n = 265) were reviewed. TTP and median OS were calculated.. Twenty-four (3.3%) of 795 randomized patients underwent curative metastatic disease resection [hepatectomy, 16; radiofrequency-ablation (RFA), six; lung resection, two]. Twenty-two out of 24 (92%) resected patients received an oxaliplatin-based regimen (FOLFOX4, 11; IROX, 11). Seven patients (29.2%) remain disease-free; relapses occurred mainly in the resected organ. Median OS in resected patients is 42.4 months, and median TTP is 18.4 months. All six patients treated with RFA have recurred. Four out of five (80%) patients who received chemotherapy following resection are disease-free.. Resection of metastatic disease after chemotherapy is possible in a small but important subset of patients with MCRC, particularly after receiving an oxaliplatin-based chemotherapy regimen, with encouraging OS and TTP observed in these highly selected patients.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Catheter Ablation; Colorectal Neoplasms; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Patient Selection; Treatment Outcome

A phase I-II multicenter trial was conducted to define the maximal tolerated dose and describe the activity of an OCFL combination using oxaliplatin (OHP), irinotecan (CPT-11) and 5-fluorouracil (FU)/leucovorin (LV) in metastatic colorectal cancer (CRC).. CRC patients not pretreated with palliative chemotherapy, with performance status < or =1 and adequate haematological, kidney and liver function, were eligible. Treatment consisted in weekly 24-h infusion 5-FU (2300 mg/m(2))/LV (30 mg) and alternating OHP (70-85 mg/m(2), days 1 and 15) and CPT-11 (80-140 mg/m(2), days 8 and 22) repeated every 5 weeks. OHP and CPT-11 were escalated in cohorts of three to six patients.. Thirty patients received a median of five cycles. Dose-limiting toxicity occurred at dose level 3, and the recommended dose was OHP 70 mg/m(2), CPT-11 100 mg/m(2), LV 30 mg and 5-FU 2300 mg/m(2)/24 h. Grade > or =3 toxicities were diarrhea 23%, neutropenia 20%, fatigue 7%, and neurologic 7%. Two febrile neutropenia episodes (one fatal) were recorded. Among 28 patients with measurable disease (90%), we observed two complete and 20 partial responses; overall RR was 78% (95% CI, 59% to 92%). Median time to progression and overall survival were 9.5 and 25.4 months, respectively. Seven patients underwent liver metastases resection.. OCFL is an overall well tolerated regimen with very high efficacy, which makes it most suitable for tumour control before surgery of metastatic disease.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Palliative Care; Prognosis; Survival Analysis; Treatment Outcome

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

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

To explore the efficacy and safety of CPT-11 combined with fluoropyrimidine in treatment for advanced or metastatic colorectal carcinoma.. From January 2001 to September 2003, 43 patients with advanced or metastatic colorectal carcinoma were randomized into two groups, group A [CPT-11 90 - 25 mg/m(2) continuous infusion for 10 h and folinic acid (FA) 30 mg x m(-2) x d(-1) + 5-FU 425 mg x m(-2) x d(-1) x 2 d continuous infusion for 48 h, every two weeks as a cycle in total of no less than six cycles] and group B (CPT-11 90 - 125 mg/m(2) continuous infusion for 10 h every two weeks as a cycle in total of no less than six cycles and capecitabine 1250 mg x m(-2) x d(-1) by oral divided into two doses, continuously taken without interruption for three months).. In this study, overall response rate (ORR) was 44.2%, disease control achieved in 83.7%, Time to progression (TTP) was 11.0 months and overall survival (OS) was 14.6 months. Response rate in group A was 31.3% and 51.9% in group B. TTP of group A was 8.4 months and that of group B was 12.5 months; OS in group A was 14.2 months and 17.9 months in group B. In 43 cases with 502 cycles of chemotherapy, grade III side effect occurred only in 3.0% and no therapy-related death occurred. Nausea and vomiting was the most common side effect with an occurrence rate of 31.9% in group A and 2 cases of grade III, and 22.7% in group B with no case of grade III. Occurrence of side effect was much lower in group B than that of group A except hand-foot syndrome, which was 16.1% in group B with 2 cases of grade III as compared to 1.4% in group A with no case of grade III.. Combination of CPT-11 and fluoropyrimidine is effective and safe in treatment for advanced/metastatic colorectal carcinoma. CPT-11 combined with capecitabine are not only more effective, but also its occurrence of side effect is lowered, and are especially high effective for lung metastasis. There is reasonable to recommend that combination of CPT-11 with capecitabine may be as first choice in treatment for such cases.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Capecitabine; Colorectal Neoplasms; Deoxycytidine; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Irinotecan; Leucovorin; Lung Neoplasms; Male; Middle Aged; Survival Rate

Pharmacokinetic modulating chemotherapy (PMC) is designed to boost high serum 5-fluorouracil (5-FU) concentrations through modulation by uracil. The therapeutic efficacy of PMC and the sensitivity of metastatic lesions to 5-FU were evaluated in advanced colorectal cancer patients.. Thirteen patients with colorectal carcinoma metastases to multiple organs were enrolled. PMC was initiated with a combination of 400 mg of uracil-tegafur daily and 24-hour continuous intravenous infusion of 600 mg/m2 of 5-FU once weekly. The 5-FU dose was escalated when the disease progressed. When PR was achieved, serum 5-FU concentrations were monitored in order to evaluate the chemosensitivity of each metastatic lesion to 5-FU.. PR in the target lesion was observed in 7 of 11, 6 of 10, 2 of 2, and 2 of 4 patients with metastatic lesions to the liver, lungs, peritoneum and lymph nodes, respectively. The area under the concentration-time curve (AUC ng x hr/ml) of the 5-FU sufficient to induce PR in pulmonary lesions, 3528 to 9684, was significantly higher than for hepatic lesions, 2413 to 6323 (p = 0.028). The median survival was 13 months.. PMC, having a chronomodulating nature, is highly effective in treating colorectal carcinoma metastases with a superior safety profile. Pulmonary metastases are more resistant to 5-FU than hepatic metastases, as they require a higher 5-FU AUC to respond.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Chronotherapy; Colorectal Neoplasms; Drug Combinations; Female; Fluorouracil; Humans; Infusion Pumps, Implantable; Infusions, Intra-Arterial; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Tegafur; Uracil

This single-centre phase I trial was designed to determine the maximum tolerated dose of irinotecan and the recommended dose to use in combination with a fixed dose of 5-fluorouracil (5-FU) administered as a protracted venous infusion, for the first-line treatment of metastatic colorectal cancer (CRC). Tolerability and efficacy were secondary end points. In all, 22 patients, median age 57 years, were treated with escalating, weekly doses of irinotecan (50, 75, 100 and 85 mg m(-2)) in combination with 250 mg m(-2) 5-FU administered as a continuous infusion. All patients had measurable disease. The combination was well tolerated up to an irinotecan dose of 75 mg m(-2). However, three out of five patients at the 100 mg m(-2) irinotecan dose level had their dose reduced due to multiple grade 2 toxicities, and eventually one patient stopped treatment due to grade 3 diarrhoea and multiple grade 2 toxicities. Subsequent patients were recruited at an irinotecan dose level of 85 mg m(-2). The overall response rate was 55%, comprising one complete and 11 partial responses (PRs). Six patients also achieved sustained stable disease (SD), giving a clinical benefit (complete response/PR/SD) response of 82%. The median duration of response was 238 days (8.5 months) and median time to progression was 224 days (8.0 months). Two patients who achieved PRs underwent partial hepatectomies. Thus, irinotecan (85 mg m(-2)) combined with a continuous infusion of 5-FU (250 mg m(-2)) is an active and well-tolerated regimen for the treatment of metastatic CRC. It represents an effective treatment for patients who require close supervision and support, throughout their initial exposure to chemotherapy for this disease, and this dose combination was recommended for an ongoing phase II study.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Dose-Response Relationship, Drug; Female; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Staging; Prognosis; Survival Rate; Treatment Outcome

Thirty-two patients with nasal NK/T-cell lymphoma and disseminated disease (lung, skin, and bone marrow) were treated with an intensive combined therapy that consisted of three cycles of CMED (cyclophosphamide 2 g/m(2), metothrexate 200 mg/m(2), etoposide 600 mg/m(2), and dexamethasone 80 mg/m(2) with leucovorin rescue administered 24 h after) every 14 d, following high-dose radiotherapy: 55 Gy in 20 sesions to centrofacial region and three cycles more of the same chemotherapy regimen. To ameliorate the presence of severe granulocytopenia, granulocyte colony-stimulating factor, 5 microg/kg, daily for 14 d, begun on d 2 after chemotherapy, was administered. Complete response was achieved in 21 cases (65%); failure or progression was observed in 11 cases (35%). With a median follow-up of 69.1 mo, relapse has not been observed; thus, actuarial curves at 5 yr showed that event-free survival (EFS) is 100% in 21 patients and overall survival (OS) is 65%. Granulocytopenia grade IV was observed in 15% cycles, Nonhematological toxicity was mild and well tolerated. Radiotherapy was well tolerated; only mild mucositis was observed. Nasal NK/T-cell lymphoma is an rare presentation of malignant lymphoma (<1% of all cases) with a worse prognosis; less than 5% patients are alive free of disease at 1 yr. The use of intensive more specific chemotherapy and high dose of local radiotherapy, appear to be an excellent therapeutic approach with improvement in EFS and OS.

Topics: Adult; Aged; Agranulocytosis; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Neoplasms; Cyclophosphamide; Dexamethasone; Disease-Free Survival; Etoposide; Female; Follow-Up Studies; Granulocyte Colony-Stimulating Factor; Humans; Killer Cells, Natural; Leucovorin; Lung Neoplasms; Lymphoma, T-Cell; Male; Methotrexate; Middle Aged; Nose Neoplasms; Radiotherapy, Adjuvant; Remission Induction; Skin Neoplasms; Treatment Outcome

The purpose of this study was to evaluate the prognostic value of quantitative dynamic FDG PET studies in patients with metastastic colorectal cancer receiving FOLFOX (fluorouracil, folinic acid and oxaliplatin) chemotherapy.. The evaluation includes 28 patients with 55 metastases from primary colorectal cancer. Reference for the FDG studies was the clinical response data, according to the WHO classification. Three response groups were defined: progressive disease (PD), stable disease (SD) and partial response (PR). The FDG studies were accomplished as dynamic series for 60 min. The evaluation of the FDG kinetics was performed using the SUV, and fractal dimension (FD) of the time activity curves based on the box counting procedure (parameter for the inhomogeneity of the tumors).. The median SUV as measured in the tumor lesions prior to onset to FOLFOX was 3.15, in comparison with 2.68 SUV after the first cycle and 2.61 SUV after the second cycle. Discriminant analysis (DA) was used for the classification of the data into the 3 categories. Both parameters SUV and FD provided 2 of the 3 "predicted" categories, namely PD and SD. It was possible to correctly classify PR in only 10% of the patients, using the FD of both studies. Generally, DA inclined to misclassify the data towards PD. Even the first PET study was predictive with respect to therapy outcome (96% for PD and 47% for SD using only the baseline SUV). Metastases with a baseline SUV lower than 4.6 did not respond to FOLFOX chemotherapy. The combination of SUV and FD of the first study lead to a correct classification of 93% of PD and 60% of SD. Best results were obtained for the FD of the initial PET study (90% for PD and 75% for SD) as well as for the FD of both studies (77% for PD, 73% for SD, 10% for PR).. Quantitative, dynamic FDG-PET should be used preferentially for monitoring patients with metastatic colorectal cancer receiving chemotherapy. Even the first FDG study prior to onset to chemotherapy is predictive for the therapy outcome.

Topics: Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Fluorodeoxyglucose F18; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Neoplasm Recurrence, Local; Neoplasm Staging; Organoplatinum Compounds; Radiopharmaceuticals; Risk Assessment; Tomography, Emission-Computed; Treatment Outcome

Irinotecan has shown activity in advanced colorectal cancer resistant to leucovorin and fluorouracil. Preclinical experiments on cell cultures and human tumor xenografts indicated potential synergy when combining irinotecan and fluorouracil. We designed a new regimen combining leucovorin, fluorouracil, irinotecan, and hydroxyurea (FOLFIRI-2) and conducted a phase II study to establish its efficacy and tolerance in advanced colorectal cancer refractory to fluorouracil and oxaliplatin. Treatment was repeated every 2 weeks and consisted of leucovorin 400 mg/m2 on day 1, immediately followed by 46 hours of continuous infusion of fluorouracil 2,000 mg/m2, irinotecan 180 mg/m2 on day 3, and hydroxyurea 1,500 mg the day before leucovorin, and on days 1 and 2. Treatment was continued until progression or limiting toxicity. Twenty-nine heavily pretreated patients entered the study. Five patients achieved an objective response (17%), and 12 obtained stabilization of disease or minor response (52%). Five patients failed to continue treatment (17%) because of toxicity or worsening condition. From the start of FOLFIRI-2 treatment, median progression-free survival was 4.1 months and median survival was 9.7 months. Grade III/IV National Cancer Institute-Common Toxicity Criteria toxicities were nausea 17%, diarrhea 31%, mucositis 14%, neutropenia 52%, and febrile neutropenia 14%. FOLFIRI-2 achieved a good rate of response and stabilization in heavily pretreated patients despite significant toxicity.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Humans; Hydroxyurea; Irinotecan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Survival Analysis

An infusional ambulatory chronotherapy with 5-FU, folinic acid (FOL) and carboplatin was administered to 45 advanced NSCLC patients. The patients were randomised into 3 groups varying according to the time of administration peak of drugs (reference hours: 4 a.m. for 5 FU (and FOL); 4 p.m. for carboplatin; +/-8 h). The reference schedule appeared best tolerated (regarding hematology and mucositis). This study has prospectively validated the chronotolerance concepts of this complex combination chemotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Chronotherapy; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Lung Neoplasms; Male; Middle Aged; Prospective Studies; Treatment Outcome

Unresectable biliary tract carcinoma (BTC) is associated with a very poor prognosis. To improve efficacy and tolerance of the 5-fluorouracil (5-FU)/cisplatin combination in BTC, we designed a new therapeutic schedule, the LV5FU2-P regimen.. Twenty-nine patients with advanced or metastatic BTC were prospectively enrolled in the study. The treatment (LV5FU2-P regimen) consisted of a biweekly administration of a 2-h infusion of leucovorin 200 mg/m(2), a 400 mg/m(2) bolus of 5-FU followed by a 22-h continuous infusion of 600 mg/m(2) 5-FU on two consecutive days and cisplatin 50 mg/m(2) on day 2. Clinical symptoms, performance and weight changes were monitored.. Objective responses were observed in 10 patients (34%) (95% confidence interval 23% to 45%) including one complete response and nine partial responses (stabilization 38%, progression 28%). Median progression-free survival and overall survival were 6.5 and 9.5 months, respectively. Weight gain was observed in 45% of patients and performance status improved in 60%. One patient had a grade 4 thrombocytopenia, and grade 3 toxicity occurred in 41% of patients. There were no treatment-related deaths.. This study, one of the largest phase II trials performed for this disease, shows that the LV5FU2-P regimen is an active and well-tolerated chemotherapy for advanced and metastatic BTC.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biliary Tract Neoplasms; Cholangiocarcinoma; Cisplatin; Female; Fluorouracil; Gastrointestinal Diseases; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neutropenia; Prospective Studies; Survival Rate; Thrombocytopenia; Treatment Outcome

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

5-fluorouracil remains the standard therapy for patients with advanced/metastatic colorectal cancer. Pre-clinical studies have demonstrated the biological modulation of 5-fluorouracil by methotrexate and leucovorin. This phase II study was initiated to determine the activity and toxicity of sequential methotrexate--leucovorin and 5-fluorouracil chemotherapy in patients with advanced colorectal cancer.. Ninety-seven patients with metastatic colorectal cancer were enrolled onto the study. Methotrexate--30 mg/m2 was administered every 6 hours for 6 doses followed by a 2 hour infusion of LV--500 mg/m2. Midway through the leucovorin infusion, patients received 5-fluorouracil--600 mg/m2. This constituted a cycle of therapy and was repeated every 2 weeks until progression.. The median age was 64 yrs (34-84) and the Eastern Cooperative Group Oncology performance score was 0 in 37%, 1 in 55% and 2 in 8% of patients. Partial and complete responses were seen in 31% of patients with a median duration of response of 6.4 months. The overall median survival was 13.0 months. The estimated 1-year survival was 53.7%. Grade III and IV toxic effects were modest and included mucositis, nausea and vomiting.. This phase II study supports previously reported data demonstrating the modest clinical benefit of 5-FU modulation utilizing methotrexate and leucovorin in patients with metastatic colorectal cancer. Ongoing studies evaluating 5-fluorouracil modulation with more novel agents (Irinotecan and/or oxaliplatin) are in progress and may prove encouraging.

Topics: Abdominal Neoplasms; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Drug Administration Routes; Drug Synergism; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Methotrexate; Middle Aged; Survival Rate; Treatment Outcome

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

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

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

In palliative first-line treatment of colorectal cancer, the secondary resection of distant metastases after downstaging has constantly gained in importance. The objective of this prospective study was to examine the tumor response rate, the toxicity, the median survival time and the prognostic impact of metastatic resection after downstaging of consecutively enrolled patients with primary nonresectable colorectal cancer treated with once weekly 24-hour (24-h) infusion of high-dose 5-fluorouracil (5-FU) and folinic acid.. Between January 1995 and July 1997, 53 consecutive patients with primary nonresectable metastases were recruited for a prospective phase II study. The patients received in out-patient care 500 mg/m2 folinic acid in the form of a 1-2-hour infusion followed by 2600 mg/m2 5-FU administered as a 24-h infusion once weekly. One treatment cycle comprised six weekly infusions followed by a two week rest. Three cycles were administered, and in the event of complete remission (CR) or partial remission (PR) and good tolerability, a fourth cycle was undertaken. Thereafter, the possibility of performing a curative metastatic resection was investigated.. Of the 53 patients treated, 7 showed a CR (13%), 15 patients a PR (28%), 26 patients stable disease (SD) (49%), and 5 patients progressive disease (PD) (10%). As the main symptom of toxicity, diarrhea (CTC grade 3 + 4) was observed in 11 patients (21%), followed by leucocytopenia (CTC grade 3 + 4) in 2 patients (4%), and the hand-foot syndrome in 1 patient (2%). The median survival time was 17 months with a median follow-up of 41 months (range: 28-59 months). In 9 patients (17%), a secondary metastatic resection was considered; in 6 patients (11%) curative resection was performed, and 4 patients (8%) showed no evidence of disease for at least three years.. In this phase II study, we have been able to show prospectively that, after downstaging by palliative treatment using a weekly 24-h infusion of high-dose 5-FU and folinic acid, secondary curative metastatic resection was technically feasible in 11% of the patients. For some of these patients, long-term survival is therefore possible. Secondary metastatic resection should be carried out in close interdisciplinary cooperation, and should be further investigated in prospective phase III studies.

Topics: Aged; Antimetabolites, Antineoplastic; Colorectal Neoplasms; Combined Modality Therapy; Female; Fluorouracil; Humans; Infusions, Intravenous; Kidney Neoplasms; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Palliative Care; Prognosis; Prospective Studies; Survival Rate

To evaluate the pharmacokinetics and toxicity of high-dose intravenous (i.v.) methotrexate (MTX) with leucovorin in patients with meningeal carcinomatosis.. Of 16 eligible patients entered on this study, 13 with meningeal carcinomatosis from breast cancer, lung cancer, or osteosarcoma were treated with MTX at loading doses of 200-1500 mg/m2, followed by a 23-h infusion of 800-6000 mg/m2. Three patients without meningeal disease were also treated and the cerebrospinal fluid (CSF) MTX concentrations were compared in patients with and without central nervous system (CNS) disease.. Patients without CNS disease had lower CSF MTX concentrations relative to the plasma MTX levels than those with CNS disease, who all had CSF MTX concentrations above the target cytotoxic concentration (1 microM). The CSF MTX concentrations correlated better with the free and the total plasma MTX concentrations than with the doses. The mean half-life of CSF MTX was 8.7 +/- 3.4 h. The mean plasma clearance of MTX was not significantly different in patients with CNS disease (84 +/- 41 ml/min per m2) versus without CNS disease (59 +/- 38 ml/min per m2). All toxicities were grade 2 or less except grade 3 hematologic toxicity. No patient had an objective response in the CSF.. This trial demonstrates that potentially cytotoxic CSF MTX concentrations (> 1 microM) are delivered safely by i.v. infusion, a less invasive and better distributed CSF therapy compared with intrathecal MTX. Because of the excellent pharmacokinetics and toxicity, high-dose i.v. MTX should be evaluated at a loading dose of 700 mg/m2 and a 23-h infusion of 2800 mg/m2 with leucovorin in less heavily pretreated patients with carcinomatous meningitis.

Topics: Adult; Breast Neoplasms; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Leucovorin; Lung Neoplasms; Male; Meningeal Neoplasms; Methotrexate; Neoplasm Metastasis; Osteosarcoma

To compare two regimens of intra-arterial chemotherapy for the treatment of hepatic metastases from colorectal cancer.. Open study.. Teaching hospital, UK SUBJECT: 57 patients with unresectable metastases confined to the liver, and an indwelling catheter in the hepatic artery.. The first 33 patients had a 24-hour intra-arterial infusion of 5-fluorouracil (5-FU) 1500 mg/m2, together with folinic acid 200 mg/m2 intravenously for the first and last two hours of the 5-FU infusion. This was repeated at weekly intervals for six weeks followed by a two-week gap before the next cycle. The remaining 24 patients had a two-weekly regimen in which folinic acid 200 mg/m2 was infused intravenously over 2 hours followed by an intra-arterial loading dose of 5-FU 400 mg/m2 over 15 minutes; 5-FU 1600 mg/m2 was then given by intra-arterial infusion over 22 hours. This was repeated on day 2 and then at two-weekly intervals.. Response rate and toxicity.. Median follow-up was 21 months, and estimated median survival 19 months. 29 patients (51%) have responded, 5 completely. There are no significant differences between the groups. Sites of progression were liver alone 26 (53%), lung alone 9 (18%), liver and lung 3 (6%), and the remainder in local or regional nodes (n = 7) or bone (n = 4). Six patients experienced WHO grade 3 or 4 toxicity.. The two regimens have high response rates and cause little systemic toxicity. Intra-arterial chemotherapy for hepatic metastases from colorectal cancer is currently being compared with conventional systemic chemotherapy in a randomised controlled trial.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Female; Fluorouracil; Humans; Infusions, Intra-Arterial; Infusions, Intravenous; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Time Factors

Ifosfamide-based chemotherapy has already been the basis of three separate clinical trials. In this study, ifosfamide was administered to lung cancer patients who had failed to respond to previous chemotherapy, to assess its response rate and toxicity.. From January 1993 to December 1996, 21 patients were treated, including eight patients with small cell lung cancer (SCLC) and 13 with non-small cell lung cancer (NSCLC). Patients who had histocytologically confirmed lung cancer, were previously treated with chemotherapy, had a measurable lesion(s), were younger than 75 years of age, had an Eastern Cooperative Oncology Group performance status of 0-3 and adequate marrow, renal and liver function were eligible for inclusion in this study. For SCLC patients, ifosfamide 2.4 g/m2 intravenous (i.v.) infusion was given over 30 minutes on days 1-3 every four weeks. For NSCLC two regimens were used: IFL (ifosfamide 2 g/m2, 5-fluorouracil (FU) 600 mg/m2 and leucovorin 50 mg/m2 i.v. infusion on days 1-3 every four weeks) and LIFE (leucovorin 50 mg/m2, ifosfamide 1 g/m2, 5-FU 400 mg/m2 and epirubicin 12 mg/m2 i.v. infusion on days 1-3 every four weeks). For NSCLC patients, IFL was used for the first two years of treatment and LIFE was used in the last two treatment years. All patients were evaluated for treatment response and toxicity.. The major toxic effect, myelosuppression (grade 3 or 4 leukopenia), occurred in 62.5% of SCLC patients and 23.1% of NSCLC patients during treatment, and in 62.5% and 10% of SCLC and NSCLC patients, respectively, throughout the course. Only one SCLC and one NSCLC patient experienced febrile neutropenia. One toxic death, attributed to febrile neutropenia, was documented in a patient with SCLC. Alopecia was ubiquitous. Other toxicities were uncommon and mild. The overall response rate was 50% in SCLC and 7.7% in NSCLC. The median time to disease progression was 61 days in SCLC and 47 days in NSCLC. Median survival was 172 days in SCLC and 173 days in NSCLC.. The study results suggest that ifosfamide chemotherapy is active with an acceptable toxicity profile in previously treated SCLC patients. However, it lacks efficacy in NSCLC patients who have been previously treated.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Epirubicin; Female; Fluorouracil; Humans; Ifosfamide; Leucovorin; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Salvage Therapy

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

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

The Oncopaz Cooperative Group designed a chemotherapy regimen to modulate UFT (Tegafur and Uracil) with leucovorin. The regimen consisted of a high intravenous dose of leucovorin, followed by oral UFT and oral leucovorin twice daily for 14 days. Based on the promising results obtained with this regimen in patients with advanced colorectal cancer, the Oncopaz group performed several phase II trials using this combination with other drugs to treat advanced gastric, lung, head and neck, and breast cancers. When combined with etoposide in gastric cancer, the regimen was shown to be active and well tolerated. However, when used with cisplatin to treat non-small cell lung cancer, a low response rate and high toxicity precluded its recommendation for further study. The addition of carboplatin in the treatment of head and neck cancer demonstrated moderate activity with low toxicity. In an ongoing trial of advanced breast cancer, preliminary results indicate that the combination of idarubicin, UFT, and leucovorin is active, with moderate, primarily hematologic toxicity. Trials of new combinations are warranted to take advantage of the pharmacokinetic properties and oral bioavailability of UFT and leucovorin.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Etoposide; Head and Neck Neoplasms; Humans; Leucovorin; Lung Neoplasms; Middle Aged; Stomach Neoplasms; Tegafur; Uracil

The aim of this study was to define the efficacy of a combination of cisplatin, 5-fluorouracil (5-FU), leucovorin, and etoposide (VP-16) in locally advanced or metastatic non-small-cell lung cancer (NSCLC). From September 1991 to November 1994, 28 patients were treated with cisplatin, 100 mg/m2 i.v. on day 1; 5-FU and leucovorin, 500 mg/m2 on days 1, 2, 3, and 4 by i.v. continuous infusion; and VP-16, 70 mg/m2 i.v. on days 1, 2, 3, and 4 (combination, PFL-VP-16). Cycles were repeated every 3 weeks. There were 22 men and six women. The median age was 58 (range, 41-76). All had measurable diseases (one was stage IIIA, six were IIIB, and 21 were IV). None had previously received chemotherapy for metastatic disease. There was one complete response and six partial responses, for an overall response rate of 25% (95% confidence interval 9-41%). The median response duration and the overall survival were 8 and 9 months, respectively. Limiting toxicity was myelosuppression and oral mucositis. Grade 3 or 4 leucopenia was observed in 20% of all of the 95 cycles administered, and oral mucositis in 13%. No grade 3 or 4 renal toxicity occurred, and neurologic toxicities were limited (3% of the 28 patients experienced grade 3). PFL-VP-16 is active and can easily be administered to patients with advanced NSCLC. However, according to the results obtained with this schedule, VP-16 does not increase either response rate or survival compared with the regimen previously described by Vokes et al. (PFL).

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Survival Rate

Brain metastases represent a common complication of breast and lung cancer, with an overall incidence exceeding 30-40% of cases. Results achieved with radiotherapy are disappointing, with a median survival of a few months, and no clear activity has been observed with chemotherapy. The aims of this study were to assess the activity and feasibility of a new chemotherapeutic approach according to the following schedule: lomustine, 80 mg/m2 day 1; carboplatin, 80 mg/m2 days 1, 8, 15, 22; vinorelbine, 20 mg/m2 days 1, 8, 15, 22; L-leucovorin 250 mg/m2 days 1, 8, 15, 22; and fluorouracil, 500 mg/m2 days 1, 8, 15, 22. Cycles were repeated every 6 weeks. Since January 1994, 28 patients have been enrolled and 26 are evaluable for response and side effects. Major patient characteristics were median age, 55 years (range 31-72); men/women 15/11; lung primary, 20; breast primary, 6; performance status Eastern Cooperative Oncology Group, 0-2. A total of 64 cycles were administered (median/patient, two cycles). Nine partial remissions have been observed (35%, 95% confidence interval 17-56%), 6 disease stabilizations, and 11 disease progressions. Median duration of response was 3 months, and median time to progression for the whole group was 3.7 months (range 1-7). Treatment was well tolerated. Mild or moderate side effects included neutropenia, thrombocytopenia, mucositis, and nausea/vomiting; grade III-IV toxicity included neutropenia and thrombocytopenia. In conclusion, our results indicate that the schedule proposed is feasible and effective in this subset of patients.

Topics: Adenocarcinoma; Adult; Aged; Antidotes; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Breast Neoplasms; Carboplatin; Female; Fluorouracil; Humans; Leucovorin; Lomustine; Lung Neoplasms; Male; Middle Aged; Remission Induction; Survival Analysis; Vinblastine; Vinorelbine

Neoadjuvant therapy in patients with Stage IIIA NSCLC is associated with a 50-70% resection rate and a 3-5 year survival of 20-32%, but few trials have required meticulous staging of the mediastinum to ensure homogeneity of the study population. Continuous infusion cisplatin 25 mg/m2/day 1-5, 5-fluorouracil 800 mg/m2/day 2-5, and high-dose leukovorin 500 mg/m2/day 1-5 (PFL) given every 4 weeks achieved a 41% response rate in metastatic NSCLC (Lynch TJ, Kalish LA, Kass F, Strauss G, Elias A, Skarin A, Shulman L, Sugarbaker D, Frei E. Continuous infusion cisplatin, 5-fluorouracil, and leukovorin for advanced non-small cell lung cancer. Cancer 1994; 73: 1171-1176). The regimen was therefore evaluated in 34 patients with pathologic Stage IIIA N2 disease between 3/91 and 10/92.. Staging consisted of chest, liver, brain computerized tomography and bone scan, bronchoscopy and surgical mediastinal node mapping. Patients received PFL for 3 cycles, followed by thoracotomy and thoracic radiotherapy (TRT) to 54-60 Gy.. Median age was 57 (42-68) years. Demographic factors included: male 56%; adenocarcinoma 59%, squamous cell carcinoma 24%; Stage T3N2 26%, T2N2 56%, and T1N2 18%. No treatment related deaths occurred. Radiographically defined response to PFL was 65% (6% complete). Thoracotomy was performed in 28 patients (82%) (6 had no attempt due to disease progression). Complete resection was achieved in 21 (75%) and seven were unresectable. Pathologic complete response was observed in five patients (15%) and an additional unresectable patient had fibrosis-only documented at thoracotomy for an overall clinicopathologic response rate of 76% (18% pathologic CR). Another ten patients had residual primary with or without hilar disease with resolution of previously documented mediastinal involvement. Six (18%) patients remain alive and disease-free with a median follow-up of 46 (33-50) months, four of whom had achieved pathologic complete response at time of surgery.. Long-term event-free survival was associated with complete surgical resection which in turn was associated with clinical response to chemotherapy. There was a possible trend associating pathologic downstaging (absent residual disease in mediastinal nodes), particularly pathologic complete response observed in patients with non-bulky mediastinal disease, with improved event-free survival. Pathologic downstaging might therefore be a useful surrogate endpoint in trials evaluating the preoperative activity of new chemotherapy regimens. While radiographic response generally correlated with findings at surgery, response as determined by histologic examination of resected tissue was generally more extensive and may more accurately reflect the systemic impact of the chemotherapy regimen.

Topics: Adult; Aged; Antidotes; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Cisplatin; Disease Progression; Female; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Survival Rate; Thoracotomy; Thorax

Doxifluridine (5-dFUR) is a fluoropyrimidine derivative, which is preferentially converted to 5-fluorouracil (5-FU) within tumour tissues. Although the activity of 5-FU in metastatic colorectal cancer is well recognised, resistance to this agent is frequently observed and remains its major limitation. The aim of this phase II study was to evaluate the activity of oral and i.v. 5-dFUR in metastatic or locally advanced colorectal cancer patients, who had been previously treated with a 5-FU containing regimen in either an adjuvant or metastatic setting. We treated 48 patients who, on the basis of tumour progression during, or within 8 weeks of the discontinuation of 5-FU therapy, were considered 5-FU resistant, 14 of the patients received 5-dFUR 3000 mg/m2 as a 1-h i.v. infusion, combined with L-leucovorin 25 mg/dose on days 1-5, every 3 weeks; the remaining 34 received oral 5-dFUR 1200 mg/m2 for 5 days followed by 5 days off. Oral L-leucovorin 25 mg/dose was administered 2 h before 5-dFUR. On the basis of WHO criteria, 4/14 (29%, 95% CI 4-51) partial responses were noted in the i.v. treated patients, and 4/34 (12%, 95% CI 1-23) in those treated orally. The radiological examinations documenting the response were a CT scan in 4 cases, ultrasound in 2 and NMR in 2. The median response duration was 6 months (range 3-11+), whereas the median time to treatment failure was 4 months (range 2-17). The responses were achieved in cases previously treated with a median of 9250 mg/m2 (range 5500-18,650) of 5-FU. No CTC-NC1 grade 4 toxicity was observed, although grade 3 diarrhoea occurred in 5 of the orally treated and in 3 of the intravenously treated patients. This is the first report documenting the efficacy of 5-dFUR in patients resistant to 5-FU therapy, and suggests that there is an absence of complete cross-resistance between these two fluoropyrimidines.

Topics: Administration, Oral; Adult; Aged; Antidotes; Antimetabolites, Antineoplastic; Antineoplastic Agents; Colorectal Neoplasms; Drug Resistance, Neoplasm; Drug Therapy, Combination; Female; Floxuridine; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Tomography, X-Ray Computed

The efficacy of chemotherapy may be affected by circadian rhythms. Therefore, we tested chronomodulated infusion (administered to coincide with relevant circadian rhythms) of oxaliplatin, fluorouracil, and folinic acid compared with a constant-rate infusion method. The combination of three drugs was delivered for 5-day courses with 16-day intervals.. We expected chronotherapy to increase objective response rate by 20% compared with constant-rate infusion. We tested this effect in a randomised multicentre trial involving patients with previously untreated metastases from colorectal cancer who were enrolled at nine institutions in three countries. 93 patients were assigned chronotherapy and 93 were assigned constant-rate infusion via multichannel programmable ambulatory pumps. The trial was interrupted when a significant difference in main outcome was reached. All data were analysed by intention to treat.. On enrollment, we found significant imbalances in two characteristics-abdominal gland or bone metastases (constant-rate infusion two patients, chronotherapy ten patients) and relapse from surgically treated metastases (constant-rate infusion seven patients, chronotherapy 22 patients). An objective response was obtained in 47 (51%) of the chronotherapy group, and in 27 (29%) of the constant-rate group (difference 21.5% [95% CI 13.7-31.2], p = 0.003). Chronotherapy reduced five-fold the rate of severe mucosal toxicity (14% vs 76%, p < 0.0001) and halved that of functional impairment from peripheral sensitive neuropathy (16% vs 31%, difference 15.0% [9.5-25.7], p < 0.01). Median time to treatment failure was 6.4 months on chronotherapy and 4.9 months on constant-rate infusion (p = 0.006), and 24% of the patients from the constant-rate infusion group received chronotherapy after failure. With a minimum follow-up of 3 years, median survival times and 3-year survival were similar in both groups (15.9 vs 16.9 months and 22% vs 21%, respectively).. Chronotherapy was significantly less toxic and more effective than constant-rate infusion. The results support the concept of temporal selectivity of cancer chemotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chronotherapy; Colorectal Neoplasms; Female; Fluorouracil; Humans; Infusion Pumps; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Peripheral Nervous System Diseases; Survival Analysis

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

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

We performed a phase II study to assess the efficacy and toxicity of the cisplatin-UFT-leucovorin (LV) combination in patients with advanced non-small-cell lung cancer (NSCLC). Twenty-five patients with measurable disease who had not received prior chemotherapy were entered into the trial. The therapeutic regimen consisted of cisplatin 90 mg/m(2) and i.v. LV 500 mg/m(2) on day 1, followed by oral UFT 390 mg/m(2)/day (in two doses on days 1 through 14. Patients also received oral LV 15 mg/12 h on days 2 through 14. Seventeen patients required reduced doses of UFT (200 mg/m(2) due to toxicity. Courses were repeated every 28 days for a minimum of three per patient. Three of 25 patients (12%) achieved a partial response (95% CI: 2.6 to 32.2%), two with 390 mg/m(2)/day and one with 200 mg/m(2)/day of UFT. The main side effects were hematological and gastrointestinal. In the courses including 390 mg/m(2)/day of UFT, grade 3-4 toxicity was leucopenia in 18% of the courses, nausea/vomiting in 27%, and diarrhea and epigastralgia in 13% each. Grade 3-4 toxicities for 200 mg/m(2)/day of UFT were leucopenia 2%, nausea/vomiting 9% and diarrhea 7%. In conclusion, this regimen cannot be recommend for the treatment of advanced NSCLC due to its low response rate and high toxicity.

Topics: Abdominal Pain; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Diarrhea; Drug Administration Schedule; Female; Humans; Leucovorin; Leukopenia; Lung Neoplasms; Male; Middle Aged; Nausea; Remission Induction; Tegafur; Vomiting

To determine the feasibility of ambulatory infusional administration 24 hours per day, 7 days per week of a three-drug regimen of cisplatin or carboplatin, leucovorin, and 5-fluorouracil (5-FU) (PLF) utilizing an alternating weekly sequential design and to introduce infusional etoposide as PLEF to the regimen.. Forty-three patients with diverse malignancies received a sequential infusion of 5-FU 200 mg/M2/day on days 1 to 14 and 21 to 35 with leucovorin admixed for day 1 to 7 and 21 to 28. Cisplatin (20 patients) or carboplatin (23 patients) infusion was administered at a dose of 10 mg/M2/day or 30 mg/M2/day, respectively, day 7 to 14 and 35 to 42. Cycles were planned to be repeated consecutively in the absence of toxicity in patients with stable or responding disease. Sixteen patients also received etoposide 30 mg/M2/day as an admixture concomitant with administration of the platinum analogue. Therefore, the distribution of therapies was PLF 19, CLF 8, PLEF 14, and CLEF 2.. A total of 63 courses of PLF +/- E was administered as outlined above. Hematologic toxicity was minimal with or without the addition of etoposide. Sixteen percent of patients developed an elevated creatinine with a median of 1.6 and a range of 1.6 to 3.2 mg %. Tumor responses were observed in seven of fourteen evaluable patients with squamous cell carcinoma of the lung (all of whom received concomitant etoposide). In addition, one patient with metastatic gallbladder cancer achieved a complete clinical response.. Ambulatory infusional PLF with carboplatin or cisplatin using sequentially alternating delivery of the component antineoplastic agents is feasible and active with minimal toxicity. The addition of infusional etoposide to the PLF regimen does not substantially increase hematologic toxicity. Extended phase II studies in aerodigestive cancers are ongoing and a phase III trial comparing this ambulatory regimen to short-term PLF infusion (5-day) may be justified to compare the relative cost and benefits of the two schedules.

Topics: Adult; Aged; Aged, 80 and over; Ambulatory Care; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Drug Administration Schedule; Etoposide; Female; Fluorouracil; Gastrointestinal Neoplasms; Hematologic Diseases; Humans; Infusions, Intravenous; Leucovorin; Lung Neoplasms; Male; Middle Aged

A crossover clinical trial between granisetron alone and granisetron combined with methylprednisolone (MPL) was undertaken for the prevention of nausea and vomiting during chemotherapy, including cisplatin, in 12 patients with advanced primary and metastatic lung cancer. The antiemetic effect was obtained in 91.7% (11/12 cases) of patients receiving granisetron alone compared to 100% (12/12 cases) of patients receiving the combination of granisetron plus MPL. Complete control of anorexia was achieved in 91.6% (11/12 cases) of patients receiving the combination compared to 58.3% (7/12 cases) of patients receiving granisetron alone. Moreover there was a significant improvement of delayed clinical symptoms including nausea, vomiting, and anorexia in the patients receiving the combination of granisetron plus MPL. Our data suggest that the antiemetic effect of the combination of granisetron plus MPL is superior to granisetron alone in patients receiving cancer chemotherapy.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cross-Over Studies; Drug Therapy, Combination; Female; Fluorouracil; Granisetron; Humans; Leucovorin; Lung Neoplasms; Male; Methylprednisolone; Middle Aged; Nausea; Vomiting

Focusing our effort on the importance of FUra scheduling we have tested the hypothesis that pulse and continuous infusion (CI) of the fluoropyrimidine have different mechanisms of cytotoxicity. Our initial approach was to compare the mechanism of resistance of a cell line resistant to a short term exposure to FUra (HCT-8/FU4hR) to that of a cell line resistant to a prolonged exposure to the fluoropyrimidine (HCT-8/FU7dR). Cytotoxicity studies showed that HCT-8/FU4hR cells were still sensitive to FUra given as a 7-d exposure, suggesting different mechanisms of resistance. Indeed, rapid recovery of TS activity after drug removal was evident in the HTC-8/FU7dR cell line while HCT-8/FU4hR cells were similar to the parental cell line with regard to both the degree of in situ TS inhibition by FUra and duration of inhibition after FUra removal. In contrast, labelling studies with [3H-6]FUra(4 h exposure, 100 microM) showed that the incorporation of the fluoropyrimidine into RNA is significantly decreased in HCT-8/FU4hR cells as compared to parental HCT-8 cells. Given the lack of cross resistance between the two schedules in vitro, a pilot trial was done on patients with colorectal cancer refractory to bolus FUra. On 15 patients failing after FUra+LV or FUra alone 1 PR, 3 MR, 3 SD and 8 P were observed, confirming a certain degree of activity of CI FUra in patients clinically resistant to bolus FUra. Based on this rationale, a phase II trial of schedule-oriented biochemical modulation of FUra in advanced colorectal cancer patients was conducted, employing a hybrid regimen of 2 biweekly cycles of FUra bolus (600 mg/sqm), preceeded by (24 h interval) methotrexate, 200 mg/sqm (in order to maximize the RNA effect of the drug) alternating with Fura continuous infusion, 200 mg/sqm daily for 3 weeks, modulated by leucovorin, 20 mg/sqm weekly bolus (in order to maximize the DNA effect). Thirty-three consecutive patients (median ECOG PS 1) with advanced measurable colorectal cancer and no prior therapy for metastatic disease entered the study, from February 1992 to August 1993. Three complete and 13 partial responses were obtained among these 33 patients (RR = 48%, 95% confidence limits, 31-66%). After a median follow-up time of 23 months, 16 patients are still alive. The median progression free survival and overall survival were 9.6 and 20.8 months, respectively. No toxic deaths or grade 4 toxicity occurred. The incidence of grade 3 toxicity per patient in any cycle was:

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Disease Progression; Disease-Free Survival; Drug Administration Schedule; Drug Resistance, Neoplasm; Fluorouracil; Humans; Infusions, Intravenous; Injections, Intravenous; Leucovorin; Liver Neoplasms; Lung Neoplasms; Methotrexate; Palliative Care; Pilot Projects; Remission Induction; Treatment Outcome; Tumor Cells, Cultured

This prospective randomized trial was performed to compare the effectiveness of intravenous vinorelbine tartrate with intravenous fluorouracil and leucovorin (5-FU/LV) on the primary end points of survival, quality of life (QOL), and relief of cancer-related symptoms in patients with advanced non-small-cell lung cancer (NSCLC). Secondary end points included tumor response rates and time to treatment failure. In addition, the safety of both treatment regimens was evaluated in this multicenter study.. Two hundred sixteen patients with stage IV NSCLC were enrolled onto this study from 18 centers. Vinorelbine was administered at a dose of 30 mg/m2/wk. 5-FU/LV was administered at a dose of 425 mg/m2 and 20 mg/m2, respectively, for 5 consecutive days every 4 weeks. Patients with progressive disease or toxicity were removed from study while responding and stable patients were continued on therapy.. The median survival time of patients who received vinorelbine was 30 weeks, with 25% of patients alive at 1 year, compared with a median survival time of 22 weeks and 16% of patients alive at 1 year for those treated with 5-FU/LV (P = .03, log-rank test). This improvement in survival was associated with a higher objective response rate (12% v 3%) and time to treatment failure (10 weeks v 8 weeks) for vinorelbine versus 5-FU/LV. The dose-limiting toxicity of vinorelbine was granulocytopenia, with 54% of patients experiencing grade 3/4 granulocytopenia. Nonhematologic toxicity of vinorelbine was generally grade 1 or 2. The most common grade 3 toxicities were related to injection-site reactions.. This trial confirms the efficacy of vinorelbine in patients with advanced NSCLC. The clinical activity and relatively favorable toxicity profile of this agent make it a reasonable and useful treatment option in the management of patients with this disease.

Topics: Adult; Aged; Aged, 80 and over; Agranulocytosis; Antidotes; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Carcinoma, Non-Small-Cell Lung; Female; Fluorouracil; Humans; Injections, Intravenous; Leucovorin; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Prospective Studies; Quality of Life; Survival Analysis; Vinblastine; Vinorelbine

Eighteen patients with non-small cell lung cancer (NSCLC) who had previously received no systemic chemotherapy, were treated on this phase II study with interferon-alfa-2b 8 MU tiw, leucovorin 500 mg/m2 IVPB over 2 hours and 5-Fluorouracil 500 mg/m2 i.v. for 6 weeks followed by a 2-week rest. There were was no rest period for interferon. Median age of patients on this study was 63 years. Fatigue, nausea, and diarrhea were the most common toxicities. There were no grade IV toxicities and no treatment-related deaths. Seven partial responses (39%) with median duration of 4.5 months were seen. An additional patient has had stable disease/minor response for 12+ months. Median survival is 10 months. ALF has activity in NSCLC.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Female; Fluorouracil; Humans; Interferon alpha-2; Interferon-alpha; Leucovorin; Lung Neoplasms; Male; Middle Aged; Recombinant Proteins

There is no known effective salvage chemotherapy for patients with refractory or relapsed urothelial tumors after methotrexate/cisplatin-based regimen. We report the results of a phase II trial with the FIFO regimen that includes from day 1 to 5: fluorouracil 350 mg/m2, folinic acid 20 mg/m2, and ifosfamide 1000 mg/m2, Q4W. Fifteen patients with metastatic measurable urothelial cancer were enrolled in this trial. Previous therapy included M-VAC regimen in 11 patients, CMV regimen in 3 patients, and both regimens in 1 patient. Thirty-one courses were delivered. Toxicity was moderate, including encephalopathy grade 2 in 2 patients and hematological toxicity grade 3 in 2 others. However, an early death occurred on day 1 in a patient who progressed rapidly and died from hepatic insufficiency after initial encephalopathy. No objective response was seen. Twelve patients progressed during FIFO therapy and 3 patients experienced a stable disease. Despite almost encouraging results of fluorouracil and ifosfamide in the literature, their combination according to our schedule is not active in urothelial cancer.

Topics: Adrenal Gland Neoplasms; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Carcinoma, Transitional Cell; Fluorouracil; Hepatic Encephalopathy; Humans; Ifosfamide; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Retroperitoneal Neoplasms; Salvage Therapy; Treatment Failure; Urologic Neoplasms

Fourteen patients with small cell lung cancer (SCLC) previously treated with one or two chemotherapy regimens were entered in this study. 5-Fluorouracil 370 mg/m2 or 300 mg/m2 was given with folinic acid 200 mg/m2 by i.v. rapid infusion on days 1 through 5. Cycles were repeated every 28 days. There were no objective responses. One patient had stable disease for 47 weeks. The overall median survival duration was 23 weeks. Toxicity was comparable to that seen in other studies of 5-fluorouracil plus folinic acid.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Female; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Remission Induction; Survival Rate

Thirty-two patients with advanced non-small cell lung carcinoma (NSCLC) received a chronomodulated 5-day venous infusion of 5-fluorouracil (5 FU) (700 mg/m2/day), folinic acid (F) (300 mg/m2/day), and carboplatin (C) (40, 50, or 55 mg/m2/day), as first chemotherapy. Courses were repeated every 21 days (after a 16-day interval). In total, 158 courses (median: 4, range: 1 through 16; 81 and 58 courses at, respectively, a 40 and 50 to 55 mg/m2 daily dosage of C) were delivered using a multichannel programmable in-time pump (Intelliject, Aguettant) connected to a double lumen implanted venous side-port. The administration was allowed in fully ambulatory convenience. Overall tolerance was excellent. Grade 3 of 4 hematologic toxicity was encountered in 4.6% of courses for thrombopenia and in 7.0% of courses for neutropenia. Nausea or vomiting (grade 3 or 4) occurred in 7.8% of courses. Mucositis, diarrhea, alopecia, or skin grade 3 or 4 toxicity were observed in less than 3% of courses. Treatment delay was needed in only 7.8% of courses and dose reductions were needed in 4.6% of courses for 5 FU and in 6.5% of courses for C. This good tolerance allowed a sustained quality of life and prompted further trials aiming to define the place of this protocol in the multidisciplinary treatment approach of NSCLC.

Topics: Adult; Aged; Ambulatory Care; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Chronobiology Phenomena; Feasibility Studies; Female; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged

In a randomized phase II study by the Cancer and Leukemia Group B, the cisplatin/5-fluorouracil/leucovorin (PFL) combination produced a 29% response rate in advanced, unresectable non-small cell lung cancer. Vinorelbine (Navelbine; Burroughs Wellcome, Co, Research Triangle Park, NC; Pierre Fabre Médicament, Paris, France), a semisynthetic vinca alkaloid, has also demonstrated single-agent activity in this disease. Therefore, a phase I-II study was designed to investigate the addition of vinorelbine in escalating doses to the PFL combination. The objectives of this study were to establish the maximum tolerated dose of vinorelbine in combination with PFL, and to define the overall response rate in a cohort of patients treated with the maximum tolerated dose. The regimen consisted of vinorelbine in escalating doses starting at 20 mg/m2/d intravenously on days 1 and 5, followed by leucovorin 100 mg orally every 4 hours on days 1 to 5,5-fluorouracil 800 mg/m2/d intravenous continuous infusion days 2 to 5 (96 hours), and cisplatin 100 mg/m2 intravenously 12 to 24 hours after administration of the first dose of vinorelbine. Cycles were repeated every 3 weeks. No dose-limiting toxicity was observed in the first five patients treated with the initial vinorelbine dose. Increasing the dose of vinorelbine to 25 mg/m2 in a second cohort of two patients, however, resulted in grade 4 granulocytopenia in both, and grade 4 diarrhea in one. It was concluded that this dose level was not feasible. During a preliminary analysis, one complete response and three partial responses were observed in 16 patients evaluated; one of these patients had a pathologic complete remission. This early analysis indicates activity for the regimen.

Topics: Adult; Aged; Agranulocytosis; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Carcinoma, Non-Small-Cell Lung; Cisplatin; Cohort Studies; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Remission Induction; Vinblastine; Vinorelbine

Fluorodeoxyuridine (FUdR), the deoxynucleoside metabolite of 5-fluorouracil (5-FU), can be converted in a single step to fluorodeoxyuridine monophosphate (FdUMP), which binds covalently to thymidylate synthase (TS). Ribonucleotide reductase, an obligatory enzyme in the synthesis of deoxynucleotides, can be inhibited by hydroxyurea. Recognizing the well-established synergism between 5-FU and folinic acid (leucovorin), we hypothesized that the simultaneous administration of FUdR, leucovorin, and hydroxyurea might afford more effective inhibition of TS. Thirty-six patients with neoplastic disease considered refractory to standard therapy were entered into this phase I protocol. Treatment was administered on days 1 through 5 of a 28-day cycle and consisted of folinic acid (500 mg m-2 day-1) and FUdR at escalating doses of 0.1, 0.15, or 0.2 mg kg-1 day-1 both administered by continuous i.v. infusion, and hydroxyurea given p.o. once per day at doses ranging from 0 to 250o mg in 500-mg increments. The hydroxyurea and FUdR levels were escalated in a sequential fashion. The majority of patients had refractory breast or lung cancer. Dose-limiting toxicities were mucositis and diarrhea at the maximally tolerated dose of 0.15 mg/kg FUdR and 2000 mg hydroxyurea per day in conjunction with high-dose folinic acid. Hematological toxicity was minor. Of the 18 patients in whom response could be evaluated, none had evidence of objective disease regression. Mucositis and diarrhea are the dose-limiting toxicities when continuous infusions of FUdR and high-dose folinic acid are combined with oral hydroxyurea, effects that are consistent with the observed toxicities for FUdR when administered alone or in combination with leucovorin.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Diarrhea; Drug Administration Schedule; Female; Floxuridine; Humans; Hydroxyurea; Infusions, Intravenous; Leucovorin; Lung Neoplasms; Male; Middle Aged; Thymidylate Synthase

In a phase I trial, 17 patients were treated with 5-fluorouracil (5-FU) 500 mg/m2 and leucovorin (LV) 500 mg/m2 intravenously weekly for 6 weeks followed by 2 weeks' rest and interferon alfa-2b 1, 3, 5, 8, or 10 million units (MU) subcutaneously tiw with no rest period. The most common toxicities were fatigue (12), diarrhea (10), nausea/vomiting (7), and fever (7). The maximum tolerated interferon dose was 8 MU tiw. Fatigue and increased incidence of other toxicities rather than a single dose-limiting toxicity occurred at the next highest interferon level. ECOG grade III/IV toxicity occurred in 5 patients and included transient supraventricular tachycardia and brief seizure episode (1), dyspnea (1), decreased performance status (1), anemia requiring transfusion (1), and deep vein thrombosis (1). No toxic deaths occurred. Two patients with non-small cell lung cancer (NSCLC) had partial responses lasting 5 and 4 months. Two other patients with NSCLC had either minor response or stable disease, and 1 patient with colon cancer had a significant decline in serum CEA. The recommended alpha interferon dose is 8 MU tiw when given with this schedule of 5-FU/LV.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluorouracil; Humans; Interferon alpha-2; Interferon-alpha; Leucovorin; Lung Neoplasms; Male; Middle Aged; Recombinant Proteins

5-Fluorouracil (5-FU) modulation with either folinic acid (FA) or methotrexate (MTX) has improved 5-FU's potential cytoreductivity. We combined MTX and FA with 5-FU to further augment 5-FU's cytoreductivity. Patients (n = 34) with advanced colorectal carcinoma were first given intravenous MTX (escalated from 30 mg/m2 to 70 mg/m2). FA (100 mg/m2) was infused 17-24 hr later, followed by 5-FU (600 mg/m2). Oral rescue doses of FA were begun 24 hr after MTX. Patients were treated every 2 weeks. No previously treated patient (n = 6) responded. Eight of the remaining 28 (29%) (95% confidence interval, 15-47%) patients achieved a PR. Median survival was 9.3 months. Toxicity (primarily gastrointestinal) necessitated dosage modification in 10 patients (29%). These results, in addition to a literature review, reveal that the manipulation of 5-FU by two modulating agents does not improve the response rate seen with single-agent modulation.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Colorectal Neoplasms; Diarrhea; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Methotrexate; Middle Aged; Remission Induction; Survival Rate; Treatment Outcome

Cisplatin, 5-fluorouracil, and leucovorin (PFL) have demonstrated synergistic activity in preclinical models. Continuous infusion of these agents maximizes the potential for synergistic interaction and forms the basis of the PFL regimen.. Sixty-one patients with advanced (Stages IIIB and IV) non-small cell lung cancer were entered into the study. Thirty-one were treated with cisplatin 25 mg/m2/day on days 1-5, 5-fluorouracil 800 mg/m2/day on days 2-6, and calcium leucovorin 500 mg/m2/day on days 1-6. Because of severe mucositis, the final 30 patients were treated with the same dosage of cisplatin but with the deletion on day 6 of leucovorin and 5-fluorouracil. Cycles were repeated every 28 days. Response was assessed after two cycles. Responding patients received an additional two cycles. Patients with Stage IIIB disease received radiation therapy to the mediastinum and sites of involved disease.. PFL had an overall response rate of 41%. Median survival was 8.1 months, and median time to treatment failure was 4.2 months. Importantly, 68% (17 of 25) of responses were maximal after just two cycles of chemotherapy. Notable toxicities included mucositis (43% > or = Grade 3) and myelosuppression. Response, time to failure, or survival did not differ between the two schedules. Mucositis was less severe with 4-day PFL.. PFL as given in this manner is an active regimen for the treatment of patients with advanced non-small cell lung cancer. The rapidity of response makes it a regimen for incorporation into protocols for Stage IIIA disease. A neoadjuvant study using PFL is underway.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Lung Neoplasms; Male; Middle Aged; Survival Analysis

Topics: Amputation, Surgical; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Chemotherapy, Adjuvant; Combined Modality Therapy; Cyclophosphamide; Disarticulation; Doxorubicin; Europe; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Neoplasm Recurrence, Local; Osteosarcoma; Survival Analysis; Treatment Outcome; Vincristine

Topics: Amputation, Surgical; Bone Neoplasms; Chemotherapy, Adjuvant; Child; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Humans; Ifosfamide; Leucovorin; Lung Neoplasms; Mesna; Osteosarcoma; Survival Analysis; Tennessee; Treatment Outcome; Vincristine

25 patients with metastatic colorectal cancer were entered into a phase II trial of combination chemoimmunotherapy using a sequential regimen of 5-fluorouracil (5-FU) and leucovorin and high-dose recombinant human interleukin-2 (rIL-2). Patients initially received three cycles of chemotherapy consisting of 500 mg/m2 of intravenous leucovorin followed by 375 mg/m2 of bolus 5-FU both given daily on days 1-5 of a 21 day cycle. Ten days after the last dose of chemotherapy in cycle 3, patients began high-dose rIL-2 at 720,000 IU/kg intravenously every 8 h to the maximum tolerated number of doses. After 7-10 days of recovery, this rIL-2 treatment was repeated to complete one full course of chemoimmunotherapy. There was no grade IV toxicity associated with 183 cycles of chemotherapy. Other than slight increases in the frequency of diarrhoea, stomatitis and hyperbilirubinaemia, rIL-2 toxicity was similar to that seen in patients given rIL-2 without chemotherapy. Of 23 evaluable patients, the overall response rate (partial + complete response) was 46% with 2 complete responses. Only 3 patients showed major tumour regression during the rIL-2 phase of therapy, but these 3 patients included both complete responders and the 3 most durable responses (15, 16 and 24 months). We conclude that sequential 5-FU/leucovorin and rIL-2 can be given safely without major increases in toxicity over either therapy alone, and although nearly all responses seen are largely attributable to chemotherapy, a contribution of immunotherapy to the minority of patients achieving complete or durable responses cannot be ruled out.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Female; Fluorouracil; Humans; Interleukin-2; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Recombinant Proteins

Topics: Aminopterin; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Cyclophosphamide; Drug Administration Schedule; Drug Evaluation; Humans; Leucovorin; Lung Neoplasms

Thirty-one patients with advanced non-small-cell lung cancer (NSCLC) were treated with a combination of folinic acid, fluorouracil, vincristine, and mitomycin (F-FOMi). Eight partial responses (26%), eight stable disease (26%), and 15 progressive disease (48%) were obtained. Patients with performance status (PS) 0-1 had a significantly better response rate than those with PS 2-3. Overall actuarial survival was 10 months. Toxicity was mild and mainly gastrointestinal with mucositis and diarrhea. F-FOMi seems to be comparable to regimens more widely used in the treatment of NSCLC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Female; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Mitomycin; Vincristine

This randomized phase II study was designed to evaluate the activity of intravenous 6-thioguanine (6-TG) as a single agent and the combination of cisplatin and 5-fluorouracil (5-Fu) modulated by oral leucovorin (PFL) in patients with advanced non-small cell lung cancer (NSCLC). Eligible patients had measurable or evaluable stage III B or IV NSCLC, had no received prior chemotherapy and had a performance status of 0-2. Patients were randomized to treatment with intravenous 6-TG at 55 mg/m2 administered over 30 minutes for 5 consecutive days and repeated every 35 days, or PFL chemotherapy with cisplatin 100 mg/m2 on day 1, 5-FU 800 mg/m2/day as a continuous intravenous infusion over 5 days and oral leucovorin administered at 100 mg every 4 hours during the entire duration of the cisplatin and 5-FU infusions. PFL was repeated every three weeks. Ninety-five eligible patients were randomized, 46 to 6-TG and 49 to PFL. Response rates were 4% for 6-TG (95% confidence interval 0.5%-14.8%, 1 partial, and 1 complete response) and 29% (16.6%-43.3%) for PFL (all partial). The median time to treatment failure was 2 and 4 months, respectively, and the median survival times were 6 and 10 months, respectively. Toxicities with 6-TG were, generally, mild to moderate but severe or life-threatening granulocytopenia was observed in 21% of patients. With PFL, mucositis was dose-limiting, and 78% of patients had severe or life-threatening mucositis. This led to dose reduction of 5-FU and leucovorin during subsequent cycles or treatment termination in 82% of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Drug Administration Schedule; Female; Fluorouracil; Follow-Up Studies; Humans; Infusions, Intravenous; Leucovorin; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Survival Rate; Thioguanine

Preclinical data suggest that both folinic acid and interferon may enhance the efficacy of 5-fluorouracil (5-FU) in colorectal carcinoma. We therefore initiated a phase I trial evaluating the doses, safety, and pharmacokinetics of the combination of recombinant interferon (IFN) alpha-2b with folinic acid (FA) and 5-FU. Seventeen patients with colorectal cancer who failed local chemotherapy received 5-FU as a 4-hour infusion, preceded by a bolus of FA and IFN. The 5-FU dose was escalated over the range of 400 to 650 mg/m2/d for a period of 7 days. Folinic acid was administered as a bolus in a fixed dose of 200 mg/m2/d and IFN as 5 million U/d subcutaneously on days 1 to 7. A total of 89 courses of therapy were completed for the 17 patients, of which there were 10 paired courses with a combination of 5-FU and IFN or 5-FU alone, being performed to analyze the pharmacokinetics and modulation of 5-FU by IFN. The maximum tolerated dose of 5-FU using this combination and a 4-hour schedule was 600 mg/m2/d for 7 days. The dose-limiting toxicity of this regimen was diarrhea. Mucositis and myelosuppression was not a marked problem at dose levels of 400 and 500 mg/m2/d for 7 days. However, at a dose level of 600 to 650 mg/m2/d for 7 days, grade 3 and 4 (WHO) leukopenia occurred in 50% and mucositis occurred in 33%. At a given dose of 5 million U, IFN did not significantly influence 5-FU serum levels. Mean steady-state serum levels of 5-FU at 500 mg/m2 given as a 4-hour infusion were 16.55 +/- 9.34 mumol/L and 18.23 +/- 12.77 mumol/L with and without IFN, respectively. Mean area under the curve (mumol/L x min) was 4,008 +/- 2,133 and 5,114 +/- 2,567 with and without interferon, respectively. Objective responses were seen in one of 17 of these heavily pretreated patients and stable disease was seen in seven of 17 patients. The recommended dose of 5-FU for use of phase II studies is 500 mg/m2/d for 7 days. We conclude that the toxicity of 5-FU plus FA with and without IFN alpha-2b can be reduced by using a 4-hour infusion instead of a bolus.

Topics: Adult; Colorectal Neoplasms; Combined Modality Therapy; Drug Administration Schedule; Drug Evaluation; Female; Fluorouracil; Humans; Infusions, Intra-Arterial; Interferon alpha-2; Interferon-alpha; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Recombinant Proteins

Based on promising results with 5-FU/FA or 5-FU/IFN-alpha in colorectal cancer, a pilot study was initiated to evaluate the effects of the combination 5-FU/FA/interferon alfa (IFN-alpha) in patients with advanced pancreatic cancer. Patients received 9 million units (MU) IFN-alpha subcutaneously three times a week or 6 MU IFN-alpha once a week; 500 mg/m2 5-FU via an intravenous bolus 1 hour after the initiation of a 2-hour infusion of 500 mg/m2 of FA, once a week. Fourteen patients, all previously untreated with chemotherapy, were enrolled; 13 (two females/11 males) were evaluable for response and toxicity (one too early). The median performance status was 80% (range, 60 to 100) and the median age 62 years. Besides the inoperable primary tumor, metastatic sites were liver, lung, and peritoneum. Three of 13 patients had a partial remission, three of 13 patients a minor response, and four of 13 patients no change. Three patients had progressive disease. Until now, no complete remission was seen. Median duration of response was 4+ months; median survival has not been reached yet. Of all patients there were three instances of World Health Organization grade 3 toxicity: fatigue (one of 13), nausea (one of 13), and diarrhea (one of 13); grade 4 toxicity did not occur. Although overall toxicity was moderate, most patients experienced a reduction of well-being. Therefore in all patients the dose of IFN was reduced (from 3 x 9 MU/week to 1 x 6 MU/week). Our preliminary data suggest that biochemical modulation of 5-FU with FA and IFN-alpha (reduced dosage) is effective in pancreatic cancer with moderate toxicity, warranting further study.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Infusions, Intravenous; Interferon alpha-2; Interferon-alpha; Leucovorin; Liver Neoplasms; Lung Neoplasms; Middle Aged; Pancreatic Neoplasms; Pilot Projects; Recombinant Proteins

Cisplatin (CDDP), 5-fluorouracil (5-FU), and hydroxyurea (HU) have individually demonstrated activity against several solid tumors, act synergistically with each other in vitro, and may act as radiation sensitizers. Therefore, we designed a phase I study to determine the maximally tolerated dose of cisplatin as given in addition to our previously described combination of 5-FU, HU, and concomitant radiotherapy (XRT). Patients exhibiting advanced solid tumors requiring palliative XRT were eligible. The regimen consisted of 1 g HU given p.o.b.i.d. on days 1-5, 600 mg/m2 5-FU given i.v. daily by continuous infusion (c.i.) on days 1-5, escalating doses of cisplatin starting at 10 mg/m2 daily given by c.i. on days 1-5, and involved-field XRT carried out on days 1-5. The cycle was repeated every 14 days until the target XRT dose had been reached. In all, 19 patients were entered at the first dose level, and cumulative grade 3-4 myelosuppression was seen in 16 subjects. As no dose escalation was feasible, the chemotherapy was subsequently altered by using the above regimen for cycles 1, 3, 5, and 7 and substituting the less myelosuppressive regimen of 1 g HU given p.o.b.i.d. on days 1-5, 400 mg/m2 5-FU given i.v. daily by c.i., and 100 mg leucovorin given p.o.4 h on days 1-5 for cycles 2, 4, and 6. On this alternating program, 28 patients were treated with escalating doses of CDDP. The dose-limiting toxicity was again myelosuppression, which was prohibitive at a CDDP dose of 20 mg/m2 daily. In the final phase of the protocol, 30 subjects were treated with the above alternating-cycle regimen at a CDDP dose of 20 mg/m2 daily and a decreased HU dose of 500 mg p.o.b.i.d. in an attempt to circumvent the myelosuppression associated with this dose of CDDP. Although severe acute toxicity (cycles 1 and 2) was observed less frequently, cumulative toxicity (all cycles) remained pronounced. The other major toxicity encountered was mucositis, which was particularly pronounced in patients receiving radiation to the head and neck and following leucovorin-containing cycles. Plasma concentrations of free platinum did not correlate with the CDDP dose, possibly due to the narrow range of doses given. Pharmacodynamic modeling demonstrated that the CDDP dose and the HU dose were associated with leukopenia. Antitumor activity was demonstrated in a number of solid tumors particularly non-small-cell lung cancer and head and neck cancer.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Drug Evaluation; Female; Fluorouracil; Head and Neck Neoplasms; Humans; Hydroxyurea; Leucovorin; Lung Neoplasms; Male; Middle Aged; Platinum

Twenty-eight patients with refractory advanced malignancies were treated with a 24-hour infusion of 5-fluorouracil (5-FU), leucovorin (LV), and N-(phosphonacetyl)-L-aspartic acid (PALA) weekly. Twenty-seven patients were evaluable to assess toxicity and antitumor activity. The PALA was administered as an intravenous bolus over 15 minutes at a fixed dose (250 mg/m2) 24 hours before the start of the 5-FU and leucovorin infusions. Initially the dose of 5-FU was 750 mg/m2; this was increased incrementally to 2600 mg/m2. The LV was administered in a fixed dose of 500 mg/m2 concurrently with the 5-FU over a 24-hour period. This regimen was repeated weekly. Diarrhea, stomatitis, nausea, and vomiting were among the dose-limiting toxicities. Others were hand-foot syndrome, hair loss of the scalp and eyelashes, overall weakness, rhinitis, and chemical conjunctivitis. The maximum tolerated dose of 5-FU in this combination and schedule was 2600 mg/m2. Seven of 14 patients treated with 2600 mg/m2 were able to tolerate the chemotherapy on a weekly basis without interruption. The other seven patients required dose reductions, but most received 5-FU at a dose of 2100 mg/m2. Twenty-three of 27 patients were treated previously. Eight patients had a partial response; five of these were treated previously. A complete response was observed in one patient with pancreatic carcinoma, previously untreated. The overall response rate for patients treated with 2100 or 2600 mg/m2 of 5-FU was nine of 18 patients (50%). Three of four previously untreated patients with pancreatic cancer responded to this treatment (two responded partially, and one had a complete response). One of three heavily pretreated patients with non-small cell lung cancer had a partial response as did a patient with breast cancer. Four of ten patients with colorectal cancer responded to the treatment (four partial responses), of whom three had been treated previously.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Aspartic Acid; Breast Neoplasms; Drug Evaluation; Female; Fluorouracil; Gastrointestinal Diseases; Gastrointestinal Neoplasms; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Neoplasms; Phosphonoacetic Acid; Prognosis

Fifty-three patients with small cell carcinoma of the lung were treated with chemotherapy and radiotherapy, 40 Gy in the chest tumour. Intrathoracic failure occurred in 89% of the cases with extensive disease and in 60% of those with limited disease. Since 86% of all failures were localized within the target volume, one can conclude that in most cases the radiation dose was too low for eradication of the tumour. The treatment technique resulted in dose inhomogeneities of more than +/- 5% in 45% of the cases. The high local failure rate might indicate the need of improved radiotherapy, in the first place higher radiation dose. However, 82% of the patients with limited disease and local failure and 50% of those without local failure also developed distant metastases. This might indicate that the curative potential of improved thoracic radiotherapy probably is limited. Besides, lethal treatment toxicity affected particularly patients in whom local cure had been achieved, indicating the difficulty of increasing the treatment intensity without increasing the lethal toxicity in potentially curable cases.

Topics: Adult; Aged; Carcinoma, Small Cell; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Female; Humans; Leucovorin; Lung Neoplasms; Male; Methotrexate; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Radiotherapy Dosage; Survival Analysis; Vincristine

Thirty patients with a diagnosis of metastatic adenocarcinoma of the lung were entered on a trial to evaluate the antitumor efficacy of 5-fluorouracil 370 mg/m2 daily for 5 days every four weeks in combination with folinic acid 200 mg/m2, 60 min prior to 5FU. All patients had a good performance status, bidimensionally measurable disease, and weight loss less than or equal to 5% of preillness weight. Of the 29 evaluable patients, only two (7%) had partial responses (95% confidence limits 1-24%). Eleven (38%) had stable disease and 16 (55%) progressed. The two responding patients survived 12 and 60+ weeks. The median survival of all evaluable patients was 25 weeks (range 7-60+) and that of the stable patients was 26 weeks. The principal toxicities observed were diarrhea and stomatitis. Myelosuppression was rarely dose limiting. In contrast to the results of treatment with 5FU and folinic acid in metastatic colorectal cancer and breast cancer, the results of treatment with this combination of agents have been much less encouraging in adenocarcinoma of the lung.

Topics: Adenocarcinoma; Adult; Aged; Allopurinol; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Diarrhea; Fatigue; Female; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Nausea; Nervous System; Stomatitis

The ongoing evaluation of combination chemotherapy with 5-fluorouracil (5-FU) and cisplatin in several tumors prompted a phase I clinical trial of cisplatin with 5-FU modulated by leucovorin. A total of 26 patients were treated with varying doses of 5-FU by continuous i.v. infusion for 5 days; 200 mg/m2 leucovorin was given by daily bolus injection for 5 days; and 20 mg/m2 cisplatin was infused over 2 h on each day of treatment. Courses were repeated every 21-28 days. The starting dose of 5-FU was 300 mg/m2. Poor-risk patients (extensive prior radiation, performance status of 2 or worse) did not tolerate the initial dose; the maximum tolerated dose of 5-FU in this group was 200 mg/m2 daily. Good-risk patients tolerated 300 mg/m2, but a majority had excessive toxicity at higher doses. The dose-limiting toxicity was gastrointestinal (mucositis/diarrhea) and/or myelosuppression; additional side effects included were nausea and vomiting (less than or equal to grade 2) and ataxia (one patient). Among 13 patients with colorectal cancer, 4 partial responses were observed. The marked reduction in the tolerable dose of 5-FU occasioned by the addition of modulating doses of leucovorin is noteworthy. The responses observed support further investigation of this regimen in phase II trials.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Colorectal Neoplasms; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Evaluation; Female; Fluorouracil; Head and Neck Neoplasms; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Prognosis

Eight patients with local Stage II (T2N1) and III (T3N0, T3N1, T2N2) small cell lung cancer received combination chemotherapy prior to elective surgery to assess the effectiveness of such a regimen in improving operability, preventing local relapse and extending survival. The regimen was well tolerated and prevented local relapse. However, the median time to recurrence of disease was 10 months and the median survival time 13 months, results which are similar to those achieved with chemotherapy and radiotherapy. Distant metastases, particularly in the brain, occurred predictably indicating that successful adjuvant surgery, despite preventing local relapse, may not afford additional survival benefit with currently available drug regimens.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Etoposide; Female; Humans; Leucovorin; Lung Neoplasms; Lymphatic Metastasis; Male; Methotrexate; Middle Aged; Neoplasm Staging; Pneumonectomy; Preoperative Care; Remission Induction; Vincristine

A total of 343 patients with previously untreated metastatic measurable colorectal carcinoma were studied to evaluate the impact on toxicity, response, and survival of leucovorin-modulated fluorouracil (5-FU). A maximally tolerated intravenous bolus loading course regimen of 5-FU alone (500 mg/m2 x 5 days every 4 weeks with 25 mg/m2 escalation) was compared with a high-dose leucovorin regimen (600 mg/m2 of 5-FU with 500 mg/m2 of leucovorin weekly for 6 weeks with a 2-week rest) and with a similar low-dose leucovorin regimen (600 mg/m2 of 5-FU with 25 mg/m2 of leucovorin weekly for 6 weeks with a 2-week rest). The dose-limiting toxicity for the two 5-FU and leucovorin regimens was gastrointestinal, specifically diarrhea; severe diarrhea was seen frequently, and treatment-related toxicity was implicated in the demise of 11 of the patients (5%). Significant improvements in response rates were observed with a response rate of 33 of 109 (30.3%) on the high-dose leucovorin regimen (P less than .01 v control); 13 of 107 (12.1%) on the 5-FU control; and 21 of 112 (18.8%) on the low-dose leucovorin regimen. A trend toward longer survival in the 5-FU plus high-dose leucovorin regimen was observed. In this study, leucovorin was shown to significantly enhance the therapeutic effect of 5-FU in metastatic colorectal carcinoma.

Topics: Aged; Clinical Trials as Topic; Colorectal Neoplasms; Drug Administration Schedule; Drug Interactions; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Prospective Studies; Random Allocation

Eighty patients with advanced gastrointestinal tumors (64% with colorectal cancer) entered a phase III prospective randomized study with 5-fluorouracil (5-FU) vs 5-FU + folinic acid (FA) The treatment included 5-FU, 600 mg/m2/week for 6 weeks, given as i.v. bolus alone (arm A), or administered by rapid injection half-way through a one-hour infusion of FA, 200 mg/m2/week for 6 weeks (arm B). Partial remission (PR) was achieved in 1 out of 30 (3%) evaluable patients for 6 months in arm A, and in 10 out of 34 (29%) patients in arm B, with a median duration of 8 months (range 6-17) (comparison of the response rate: P = 0.005). In patients with colorectal cancer the response rate was 5% and 27% in arm A and in arm B respectively (P = 0.06). Two patients, who were resistant to 5-FU alone, achieved PR after treatment with 5-FU + FA. Diarrhea was observed in 14/42 patients (33%) in arm B (grade 1-2 in 10 and grade 3 in 4) and in 2/38 patients (5%) in arm A (P = 0.005). Other side effects such as nausea/vomiting, myelosuppression and stomatitis were infrequent and of mild intensity in both arms. No statistical difference in survival was detected when comparing the two groups (estimated median survival 8 months and 11 months for arm A and arm B respectively). These results seem to indicate that the weekly regimen of 5-FU + FA has a superior response rate compared to 5-FU alone, and that it is well tolerated. However, the advantage is not reflected in overall survival.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Female; Fluorouracil; Gastrointestinal Neoplasms; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Pelvic Neoplasms; Prospective Studies; Randomized Controlled Trials as Topic

Chemotherapy with leucovorin (100 to 200 mg) and 5-fluorouracil (30 mg/kg) every 2 wk produced four (three complete) objective responses among a group of eight patients with early metastatic pancreatic primary and unknown cancers. Complete remissions were associated with exceptionally long durations of survival, one in a patient failing prior combination chemotherapy. This treatment warrants testing because of its ease, scientific rationale, and the large population of patients with early metastatic pancreatic cancer for whom there is no accepted treatment. Early metastatic disease is defined as small metastatic lesions not immediately life threatening found in a physiologically intact patient. Controlled trials, demonstrating benefit associated with other 5-fluorouracil-containing regimens for patients with nonmetastatic stages of pancreatic cancer, provide a rationale for extending testing of leucovorin and 5-fluorouracil to other early stages of pancreatic cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Clinical Trials as Topic; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Middle Aged; Neoplasms, Unknown Primary; Pancreatic Neoplasms

Two hundred and thirty five patients with osteosarcoma, aged less than 40 years, and treated by amputation or radiotherapy, were entered in a randomised trial of two forms of adjuvant chemotherapy. A two drug regimen, namely vincristine 2 mg m-2 (maximum 2mg) followed by methotrexate 200 mgm-2, given every three weeks, was compared with a three drug regimen, comprising the same vincristine-methotrexate treatment, alternating every three weeks with doxorubicin 60 mg m-2. Both regimens were continued for 54 weeks. Forty-one patients were excluded, most because of inadequate histology, leaving 194 patients for analysis. One hundred and seventy of these had immediate amputation, 14 were treated by a policy of radiotherapy, with surgery delayed for 9 months, provided no distant metastases had appeared, and 10 by a policy of radiotherapy only. Patients have been followed-up for between 26 and 94 months after entry to the trial. The 2- and 5-year survival rates were 48% and 27%. No significant difference in survival was observed between the two regimens, but toxicity was less with the two drug regimen.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Child; Combined Modality Therapy; Doxorubicin; Female; Humans; Leucovorin; Lung Neoplasms; Male; Methotrexate; Osteosarcoma; Prognosis; Vincristine

A randomized two-arm study was undertaken to determine relative tumoricidal effects of intra-arterial cis-diamminedichloroplatinum II (I/A-CDP) and high-dose methotrexate with citrovorum factor rescue (MTX-CF) in the treatment of the primary tumor in patients with osteosarcoma. Responses were evaluated by clinical, radiographic, angiographic, and pathologic parameters. Fifteen patients were randomized to receive MTX-CF and 15 to I/A-CDP. In the MTX-CF arm there were four responses (three complete responses, one partial response) whereas in the I/A CDP arm there were nine responses (seven complete responses, two partial responses). Two patients who failed MTX-CF and requested alternative treatment with I/A-CDP also responded. The total I/A-CDP response was 11/17.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Child; Child, Preschool; Cisplatin; Humans; Infusions, Intra-Arterial; Leucovorin; Lung Neoplasms; Methotrexate; Osteosarcoma; Random Allocation

Patients with visceral patterns of metastatic breast cancer were stratified according to dominant metastatic site and performance status and then randomized to therapy with cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF) or CAF alternating with a "cell-cycle active" regimen including cytosine arabinoside, methotrexate with leucovorin rescue, and oncovin ( CAMELEON ). One hundred eighty-seven patients were randomized; response rate for CAF was 44% and for CAF + CAMELEON , 40%. Durations of disease control and survival were not significantly different. Toxicity of CAF was as anticipated with predominant granulocytopenia, vomiting, and alopecia. Toxicity of CAMELEON was less severe than that of CAF, and CAF toxicity was not worsened by preceding courses of CAMELEON ; however, the CAF- CAMELEON regimen was cumbersome and complex leading to both physician and patient noncompliance. Contrary to the preliminary results of a pilot study, and preliminary reports of the present trial suggesting benefit for the CAF- CAMELEON regimen the present randomized trial does not confirm any significant benefit of CAF- CAMELEON over CAF alone in patients with visceral metastatic breast cancer although this conclusion must be viewed in light of the high inevaluability rate due to patient and physician noncompliance.

Topics: Agranulocytosis; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Clinical Trials as Topic; Cyclophosphamide; Cytarabine; Doxorubicin; Drug Administration Schedule; Drug Resistance; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Methotrexate; Nausea; Random Allocation; Thrombocytopenia; Vincristine; Vomiting

In order to determine whether combination chemotherapy offered any advantage over single-agent therapy in cases of metastatic non-small cell bronchogenic carcinoma, we performed a randomized study in 56 patients comparing combination chemotherapy (cyclophosphamide, doxorubicin, methotrexate, procarbazine, leucovorin--CAMP-L) with a regimen in which the same drugs were given sequentially (methotrexate/leucovorin followed by cyclophosphamide/doxorubicin at progression). Of the patients receiving the combination, 52% (14 of 27) had either a partial response or stable disease, compared to 17% (5 of 29) in the sequential group. Of the patients with adenocarcinoma, those in the combination group had a significantly longer survival than those treated in the sequential group (medians, 10.0 vs 2.8 months; P less than 0.01); such a difference could not be demonstrated for patients with squamous carcinoma. Patients who achieved a partial response had a median survival of 15.3 months; those with stable disease survived a median of 10.0 months; and those with no response survived a median of 2.5 months (P less than 0.0001). Four patients died from chemotherapy-related complications: three from methotrexate toxicity and resultant infection and one from pneumonia associated with neutropenia. We conclude that the short survival of non-responding patients and the survival benefit accompanying response or stabilization make early aggressive combination therapy useful for patients with metastatic non-small cell lung cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Bronchogenic; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Clinical Trials as Topic; Cyclic AMP; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Female; Humans; Leucovorin; Lung Neoplasms; Male; Methotrexate; Middle Aged; Neoplasm Metastasis; Procarbazine

Since 1974, 120 previously untreated patients with small cell carcinoma of the lung seen in Therapeutic Radiology at The Medical College of Wisconsin have been entered into one of 4 successive studies. Study I used thoracic irradiation (TI) alone (4500-6000 rad in 3-6 weeks) with chemotherapy at progression. Study II randomized patients with limited disease to TI (3000 rad in 2 weeks) plus either cyclophosphamide, doxorubicin, vincristine (CAV) or total body irradiation (TBI); patients with extensive disease received TI + CAV. Study III employed prophylactic cranial irradiation (PCI) plus CAV and withheld TI unless there was incomplete response or recurrence. Of 93 evaluable patients from the first three studies, 55 had limited and 38 extensive disease. Study I (37 patients) showed a 62% complete response (CR) rate; 43% failed in the chest, 14% had brain metastases, and the median survival was only 22 weeks in spite of a preponderance of limited disease patients. Study II (27 patients) showed a CR of 59%; 30% had brain metastases and the median survival was 48 weeks. Study II patients (29) had a 69% rate; 72% failed in the chest, 4% with PCI developed brain metastases, and the median survival was 50 weeks. In March, 1979, Study IV was initiated; patients receive PCI (2500 rad in 2 weeks) plus high dose CAV, methotrexate and leucovorin. After 6 cycles, consolidation TI (3750 rad in 3 weeks) is given to patients with complete response. Preliminary results with 27 patients treated on this study show a 67% CR rate, a 41% chest failure rate (but only 11% for the patients who received thoracic irradiation) and no intracranial failures, but a 13% extracranial CNS failure rate. PCI, TI and spinal irradiation may be necessary to maximize the probability of long term disease free survival.

Topics: Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Carcinoma, Small Cell; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Female; Humans; Leucovorin; Lung Neoplasms; Male; Methotrexate; Middle Aged; Radiotherapy Dosage; Vincristine; Whole-Body Irradiation

A comparison is made between four different but similar approaches to the chemotherapy of 250 patients with nonoat cell bronchogenic carcinoma of the lung. Combination chemotherapy, particularly in regimen where platinum is included, provided no significant advantages over single agent chemotherapy. Side effects attributed to platinum tend to distract from any modest therapeutic gains achieved through its use. Responses rates were not significantly increased through use of platinum in the chemotherapy combination reported in this study.

Topics: Carcinoma, Bronchogenic; Cisplatin; Clinical Trials as Topic; Cyclophosphamide; Drug Evaluation; Drug Therapy, Combination; Humans; Leucovorin; Lomustine; Lung Neoplasms; Methotrexate; Neoplasm Staging; Prognosis

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

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

Topics: Bone Neoplasms; Clinical Trials as Topic; Doxorubicin; Drug Therapy, Combination; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Osteosarcoma

A randomized trial of combined modality therapy employing combination chemotherapy (cyclophosphamide (CTX) and methotrexate (MTX), CTX, MTX and Vincristine (VCR) and CTX, VCR and high-dose MTX with citrovorum rescue) and radiation therapy was compared to cyclophosphamide and radiation therapy in 258 patients with pulmonary small cell carcinoma. Patients were also rendomized: 1) to determine the effects of prophylactic whole brain irradiation; and 2) to establish the effects of maintenance chemotherapy. Survival, frequency of response and site of relapse were different in patients with limited disease (LD) (disease confined to lung, mediastinum and supraclavicular lymph nodes) when compared with disease spread beyond these sites (extensive disease) (ED). No survival advantage was seen in LD when combination chemotherapy was employed, although the frequency of complete remission was greater with three drugs than with one or two drugs (40% vs. 32%). In ED frequency of response was greater for three drugs than for one and two drugs (60% vs. 40%), but there was no survival advantage. The median survival time for complete responders was similar for limited or extensive disease (12.1 months), but 23.8% were alive at 24 months with LD compared to none with ED. Maintenance chemotherapy significantly prolonged survival by 16.8 months with 33% alive at 24 months compared to 9% who were unmaintained. Prophylactic while brain irradiation prevented brain metastases with only 4% developing this complication as compared to 18% of control subjects, but did not influence survival.

Topics: Antineoplastic Agents; Brain Neoplasms; Carcinoma, Small Cell; Clinical Trials as Topic; Cyclophosphamide; Drug Therapy, Combination; Female; Humans; Leucovorin; Lung Neoplasms; Male; Methotrexate; Middle Aged; Random Allocation; Remission, Spontaneous; Time Factors; Vincristine

Combination chemotherapy appears superior to single-agent therapy in treating a wide variety of tumors. Encouraged by this data, we conducted a pilot study using cyclophosphamide, adriamycin, intermediate dose methotrexate and folinic acid rescue (CAMF) in patients with advanced lung cancer. Forty-eight patients with unresectable tumors were entered on this trial, and treated with 500 mg/m2 intravenously administered cyclophosphamide, 50 mg/m2 intravenously administered adriamycin, 40--200 mg/m2 orally administered methotrexate (4 doses/24 hrs), and 5 mg orally administered folinic acid (6 doses/36 hrs); this regimen was repeated every three weeks if tolerable. There were 43 patients evaluable for toxicity and 34 (non-small types) for response. The major toxicities were myelosuppression and nausea and vomiting. The overall response rate (complete and partial responses) was 29.4% (10/34) and in 13 patients (38%), the disease was stabilized. Those responding had a median survival time of 10.5 months versus 4 months for nonresponders. Patients in whom the disease was stabilized had a median survival time of 8 months. CAMF is a well-tolerated drug combination with promising results in patients with advanced lung cancer.

Topics: Adult; Aged; Antineoplastic Agents; Bone Marrow; Clinical Trials as Topic; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Middle Aged; Vomiting

Topics: Antineoplastic Agents; Bone Marrow; Bone Marrow Transplantation; Carcinoma, Small Cell; Clinical Trials as Topic; Drug Therapy, Combination; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Recurrence; Remission, Spontaneous; Research Design; Time Factors; Transplantation, Autologous

Nineteen patients with non-small-cell carcinoma of the lung were treated with high-dose methotrexate and leucovorin rescue. Two partial responses (10.5%) were observed, lasting 13 and 17 weeks. Toxicity was acceptable. It is concluded that the occasional benefit of high-dose methotrexate with leucovorin rescue at this dose and according to the schedule described for these patients does not warrant further study.

Topics: Adult; Carcinoma; Clinical Trials as Topic; Drug Therapy, Combination; Female; Humans; Leucovorin; Lung Neoplasms; Male; Methotrexate; Middle Aged

A radomized clinical trial of chemotherapy, immunization and immunochemotherapy among 55 patients with stages I and II carcinoma of the lung is reported. The survival rate in the immunized groups was significantly better (P = 0.001) than that in the nonimmunized groups. The results are discussed in the light of the reactivity of the patients to the specific cancer antigen.

Topics: Adult; Aged; Antigens, Neoplasm; Female; Humans; Hypersensitivity, Delayed; Immunotherapy; Leucovorin; Lung Neoplasms; Male; Methotrexate; Middle Aged

Topics: Adolescent; Adult; Amputation, Surgical; Antineoplastic Agents; Bone Neoplasms; Cell Division; Child; Clinical Trials as Topic; Doxorubicin; Drug Therapy, Combination; Female; Humans; Leucovorin; Lung Neoplasms; Male; Methotrexate; Neoplasm Metastasis; Osteosarcoma; Prognosis; Radiotherapy, High-Energy; Time Factors

After surgical resection of their primary lung cancer, 33 patients were randomized into one of three groups. The first received high-dose methotrexate once per month with citrovorum rescue, for 3 months. The second group were immunized monthly with a homogenate of Freund's complete adjuvant and carefully characterized soluble antigen derived from allogeneic lung cancer cells of appropriate histology, for 3 months. The third group received a combination of methotrexate and immunization monthly, for 3 months. Each patient was monitored immunologically before, during, and after the treatment period, by use of delayed hypersensitivity reactions to recall and cancer antigens, in vitro lymphocyte response to mitogens, and mixed lymphocyte blocking factor activity. The group that received methotrexate showed little change in skin reactivity, a reduction of blocking factor activity, and significant rebound overshoot in in vitro lymphocyte performance. The immunized group showed a tendency to production of blocking factor activity, striking conversion and enhancement of skin reactivity, and little change in in vitro lymphocyte performance. The immunochemotherapy group showed dramatic increases in specific skin reactivity to cancer antigens, up to 2 years after treatment, in vitro lymphocyte rebound overshoot, and reduction of blocking factor activity production. Classic life table analysis of the probability of freedom from metastases in patients with stage-I cancer indicate that the disease-free interval in patients who received methotrexate is longer than in historic and concomitant controls but not as long as in those who received immunization. The best group appear to be those who received combination immunochemotherapy. We emphasize that the small numbers in this pilot study do not yet allow firm conclusions to be made.

Topics: Adult; Aged; Antigens, Neoplasm; B-Lymphocytes; Female; Freund's Adjuvant; Humans; Hypersensitivity, Delayed; Immunotherapy; Leucovorin; Lung Neoplasms; Male; Methotrexate; Middle Aged; T-Lymphocytes

Topics: Amputation, Surgical; Bone Neoplasms; Clinical Trials as Topic; Drug Therapy, Combination; Femoral Neoplasms; Follow-Up Studies; Humans; Injections, Intramuscular; Injections, Intravenous; Leucovorin; Lung Neoplasms; Methotrexate; Neoplasm Metastasis; Osteosarcoma; Time Factors; Vincristine

Oral folic acid supplementation is essential for patients treated with pemetrexed, to prevent the risk of severe hematologic toxicity. In case of intestinal absorption disorder, no recommendations exist for intravenous folic acid supplementation.. We describe a 74-year-old patient with multimetastatic non-small-cell lung adenocarcinoma, receiving first-line chemotherapy with carboplatin AUC5, pemetrexed 500 mg/m. Intravenous injection of 200 mg levoleucovorin on day 1 of cycle 1 of pemetrexed-based chemotherapy was administered and well tolerated. During the second cycle, the levoleucovorin perfusion was not renewed by omission. The patient was hospitalized for 7 days because of febrile aplasia. Piperacillin-tazobactam was started, and then switched to amoxicillin-clavulanate plus ciprofloxacin. After this episode of post-chemotherapy febrile aplasia, it was decided to systematically supplement the patient with intravenous levoleucovorin, with blood folate concentration monitoring at each cycle. At 16 months after start of treatment, the patient was in complete remission, indicating that the immune-chemotherapy was effective, with no further febrile neutropenia.. This case report highlights intravenous levoleucovorin supplementation as an alternative to oral folic acid if needed during pemetrexed

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Celiac Disease; Dietary Supplements; Folic Acid; Humans; Injections, Intravenous; Levoleucovorin; Lung Neoplasms; Pemetrexed

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

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

Topics: Antineoplastic Combined Chemotherapy Protocols; Humans; Leucovorin; Lung Neoplasms; Neutropenia; Pemetrexed

Late-stage elderly patients have low tolerance to chemotherapy, and they have difficulties when they are treated with standard chemotherapy. We report a case of a late-stage elderly patient who had a long-term response to UFT/UZEL/bevacizumab( Bev)therapy for lung metastasis after surgery for early-stage colon cancer. He was 82-years-old and underwent laparoscopy-assisted sigmoid colectomy for sigmoid colon cancer at another hospital. The pathological diagnosis was pT1b, ly1, v0, N0, M0, pStage Ⅰ. Six months after the surgery, a small nodule was noted in the middle lobe of the right lung. It grew five months later and was definitely diagnosed as lung metastasis. Considering his physical condition and tumor size, we opted to introduce less invasive chemotherapy instead of standard chemotherapy. UFT/UZEL/Bev was started 14 months after surgery. Although he required dose reduction due to anorexia, he safely continued the treatment with partial response (PR), which was maintained for 2 years and 6 months. While UFT/UZEL/Bev has no convincing evidence, it may be an option for vulnerable patients, especially those with non-life-threatening disease.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Humans; Leucovorin; Lung Neoplasms; Male; Sigmoid Neoplasms; Tegafur; Uracil

We hereby report a case in which a patient with multiple lung metastases of pancreatic cancer continued chemotherapy and maintained good performance status(PS)for 48 months after recurrence. But her disease progressed rapidly after withdrawal of chemotherapy, resulting in her death in a short period of time. The patient was a 66-year-old woman who underwent a substomach preserving pancreaticoduodenectomy for pancreatic head cancer at the age of 60 years. She was diagnosed as fT3N1M0, fStage ⅡB. During postoperative adjuvant chemotherapy S-1, multiple lung metastases were noted on CT scan 2 years after surgery. Thereafter, she was treated with gemcitabine(GEM)alone, GEM plus nab-paclitaxel(GnP), nal-CPT-11 plus 5-FU plus Leucovorin, and FOLFIRINOX for 48 months sequentially. Each of which achieved a best overall response SD or better. However, Trousseau syndrome developed following community-acquired pneumonia during chemotherapy withdrawal due to myelosuppression. The disease progressed rapidly and resulted in her death 50 months after relapse. The results suggest that chemotherapy may have contributed significantly to disease control in this case.

Topics: Aged; Albumins; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Female; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Middle Aged; Neoplasm Recurrence, Local; Paclitaxel; Pancreatic Neoplasms

We aimed to compare weekly methotrexate (MTX) regimen and methotrexate-folinic acid (MTX-FA) 8-day regimen in the first line treatment of low-risk gestational trophoblastic neoplasia (GTN).. The median age of all patients was 29 (18-51) years, and the median FIGO risk score was 3 (1-6). Of the patients recruited, 53 received MTX-FA 8-day, and 20 had MTX weekly regimens. There was a significant difference between the two groups with respect to FIGO risk scores (3 [1-6] vs. 2 [1-5], p = 0.023, MTX-FA 8-day vs. MTX weekly, respectively). The complete response rate was significantly higher in MTX-FA 8-day group compared to MTX weekly group (83% [44/53] vs. 60% [12/20] p = 0.038). In univariate and multivariate regression analyses, only presence of lung metastasis was found to be an independent risk factor for treatment resistance (OR: 3.959, 95% CI 1.105-14.179, p = 0.035).. MTX-FA 8-day regimen is more effective than weekly MTX regimen in the first line treatment of low-risk GTN including patients even with higher FIGO risk scores. Treatment resistance may develop especially in patients with lung metastasis.

Topics: Adult; Female; Gestational Trophoblastic Disease; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Middle Aged; Pregnancy; Retrospective Studies

Retrospective studies suggest a survival benefit when platinum-based chemotherapy is administered to patients with pancreatic cancer harbouring a germline mutation in BRCA1, BRCA2 or PALB2 (mut-positive PDAC). However, the objective response rate (ORR) and real-world progression free survival (rwPFS) achieved with such treatment remain ill-defined.. Twenty-six patients with advanced-stage mut-positive PDAC who had been treated with platinum-based therapy were matched by age, race and sex to 52 platinum-treated control PDAC patients. Responses to therapy were determined by RECIST v1.1, performed by blinded radiology review. Measured outcomes included ORR and rwPFS.. The ORR in mut-positive patients was 58% compared to 21% in the control group (p = 0.0022). There was no significant difference in ORR between platinum regimens in mut-positive patients (p = 0.814), whereas in control patients, the only observed responses were to FOLFIRINOX. rwPFS was 10.1 mo. for mut-positive patients and 6.9 mo. for controls (HR 0.43; 95% CI 0.25-0.74; 0.0068).. Mut-positive PDAC has a high ORR and prolonged rwPFS to platinum-based chemotherapy. These findings may have implications particularly in the neoadjuvant setting, and for future clinical trial design, and highlight the importance of early germline testing in patients with PDAC.

Topics: Adult; Aged; Aged, 80 and over; Albumins; Antineoplastic Combined Chemotherapy Protocols; BRCA1 Protein; BRCA2 Protein; Carcinoma, Pancreatic Ductal; Case-Control Studies; Cisplatin; Deoxycytidine; Fanconi Anemia Complementation Group N Protein; Female; Fluorouracil; Gemcitabine; Germ-Line Mutation; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Paclitaxel; Pancreatic Neoplasms; Prognosis; Progression-Free Survival; Retrospective Studies

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

Some metastatic colorectal cancer (mCRC) patients receive conversion surgery (CS), including metastasectomy after palliative chemotherapy. Although targeted agents significantly improved the outcomes, the clinical outcome of CS in the targeted agent era has not yet been thoroughly investigated.. We analyzed the clinical data of 96 mCRC patients who initially had unresectable liver- and/or lung-limited metastases and underwent first-line cetuximab or bevacizumab plus FOLFIRI between January 2013 and June 2017.. Liver-limited metastasis was seen in 44 patients (45.8%), lung-limited metastases in 21 patients (21.9%), and both liver and lung metastases in 31 patients (32.3%). Among them, 37 patients (38.5%) received cetuximab, and 59 patients (61.5%) received bevacizumab plus FOLFIRI. Overall response rate was 63.9% and 40.7%, respectively (p = 0.035). After median 8.7 (range 2.5-27.3) months, CS was performed in 11 patients (29.7%) in cetuximab group and 15 patients (25.4%) in bevacizumab group (p = 0.646). Median overall survival has not been reached in R0-resected patients (n = 23), during the median follow-up period of 22.5 (range 9.8-54.5) months. Median disease-free survival was 7.1 (95% CI 2.5-11.7) months: 11.0 (95% CI 3.1-19.0) months in cetuximab group and 3.2 (95% CI 0.0-7.8) months in bevacizumab group (p = 0.422). There was no progression after 18.5 months and disease-free survival reached a plateau at 19.9%.. A substantial proportion of patients could receive CS after cetuximab or bevacizumab plus FOLFIRI chemotherapy. R0-resected patients had excellent overall survival, although 80.1% of them eventually experienced recurrence. Some patients could achieve durable disease-free state.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Cetuximab; Colorectal Neoplasms; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Liver; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Retrospective Studies

To evaluate the incidence of pulmonary metastases on chest computed tomography (CT) in patients with locally advanced pancreatic cancer (LAPC).. All patients diagnosed with LAPC in a single tertiary center (Erasmus MC) between October 2011 and December 2017 were reviewed. The staging chest CT scan and follow-up chest CT scans were evaluated. Pulmonary nodules were divided into three categories: apparent benign, too small to characterize, and apparent malignant.. In 124 consecutive patients diagnosed with LAPC, 119 (96%) patients underwent a staging chest CT scan at the initial presentation. In 88 (74%) patients no pulmonary nodules were found; in 16 (13%) patients an apparent benign pulmonary nodule was found, and in 15 (13%) patients a pulmonary nodule too small to characterize was found. Follow-up chest CT scan(s) were performed in 111 (93%) patients. In one patient with either no pulmonary nodule or an apparent benign pulmonary nodule at initial staging, an apparent malignant pulmonary nodule was found on a follow-up chest CT scan. However, a biopsy of the nodule was inconclusive. Of 15 patients in whom a pulmonary nodule too small to characterize was found at staging, 12 (80%) patients underwent a follow-up CT scan; in 4 (33%) of these patients, an apparent malignant pulmonary nodule was found.. In patients with LAPC in whom at diagnosis a chest CT scan revealed either no pulmonary nodules or apparent benign pulmonary nodules, routine follow-up chest CT scans is not recommended. Patients with pulmonary nodules too small to characterize are at risk to develop apparent malignant pulmonary nodules during follow-up.

Topics: Aged; Albumins; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Female; Fluorouracil; Gemcitabine; Humans; Irinotecan; Leucovorin; Lung Neoplasms; Male; Middle Aged; Multiple Pulmonary Nodules; Neoplasm Staging; Oxaliplatin; Paclitaxel; Pancreatic Neoplasms; Radiosurgery; Retrospective Studies; Tomography, X-Ray Computed

To explore the relationship between fatigue and self-efficacy, and quality of life (QoL) during chemotherapy of patients with breast, lung or gastrointestinal cancers. This study is a descriptive-correlational research. The study population comprised of patients with breast, lung and gastrointestinal cancer treated at the outpatient chemotherapy unit. Patients' self-efficacy and QoL were assessed using Functional Assessment of Chronic Illness Therapy-Fatigue scale and Strategies Used by Patients to Promote Health scale. The sample included 236 patients receiving chemotherapy for lung cancer (30.9%), gastrointestinal (25.8%) or breast cancers (25.4%). The patients had little confidence in performing self-care self-efficacy during chemotherapy for the management of illness and chemotherapy-related side effects. The study found that the patients with cancer were moderately fatigued and all the domains of QoL of patients with cancer undergoing chemotherapy were considerably impaired. Positive correlations were found between self-efficacy scores and fatigue scores (p < 0.001), and QoL scores (p < 0.001). Better self-efficacy beliefs were associated with better QoL and lower fatigue. Improving the cancer patients' self-confidence in performing self-care behaviours may have a positive impact on performing cognitive and behavioural fatigue management strategies and can influence positively the patients' QoL during chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Colorectal Neoplasms; Fatigue; Female; Fluorouracil; Gastrointestinal Neoplasms; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Paclitaxel; Quality of Life; Self Care; Self Efficacy; Surveys and Questionnaires; Turkey

Topics: Antineoplastic Combined Chemotherapy Protocols; Biopsy; Camptothecin; Colonic Neoplasms; Drug Eruptions; Female; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Middle Aged; Panitumumab; Prednisolone; Purpura; Skin; Staphylococcal Skin Infections; Staphylococcus aureus; Vasculitis, Leukocytoclastic, Cutaneous

To compare treatment with hepatic arterial infusion of chemotherapy (HAIC) in patients with advanced hepatocellular carcinoma (HCC) with both extrahepatic spread (EHS) and intrahepatic tumor and patients with intrahepatic tumor only.. This single-center retrospective study comprised 116 patients with advanced HCC with both intrahepatic tumor and EHS (EHS group; n = 50) or with intrahepatic tumor only (non-EHS group; n = 66) treated with HAIC including oxaliplatin, fluorouracil, and leucovorin between June 2014 and July 2016. Overall survival (OS) and radiologic responses to treatment were determined and compared between the 2 groups.. Both the objective response rate and the clinical benefit rate were higher in the non-EHS group than in the EHS group (37.9% vs 16% objective response rate, P = .010; 81.8% vs 62% clinical benefit rate, P = .017). Median OS was not statistically different between the 2 groups (14.8 months vs 9.8 months, P = .068). Subgroup analysis of OS found that patients with lung metastases survived for a shorter time (OS 7 months) than patients with other metastatic sites (P = .003) and patients free of metastases (P = .001).. HAIC is a potential treatment option for advanced HCC with limited extrahepatic metastases in a population with hepatitis B virus infection.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; China; Clinical Decision-Making; Female; Fluorouracil; Hepatic Artery; Humans; Infusions, Intra-Arterial; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Oxaliplatin; Patient Selection; Retrospective Studies; Time Factors; Treatment Outcome; Young Adult

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

We present the case of a 59 year old patient with a rare mutation in BRAF codon 594, who progressed rapidly on all classical therapies but experienced a clear and long lasting response on treatment with Regorafenib.. Little is known about therapies that can be effective in the rare

Topics: Adenocarcinoma of Lung; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Biomarkers, Tumor; Carcinoembryonic Antigen; Cetuximab; Colonic Neoplasms; Exons; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Mutation; Organoplatinum Compounds; Phenylurea Compounds; Proto-Oncogene Proteins B-raf; Pyridines; Tomography, X-Ray Computed; Treatment Outcome

Topics: Adenocarcinoma of Lung; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Combined Modality Therapy; Female; Fluorouracil; Hepatic Artery; Humans; Immunotherapy; Infusions, Intravenous; Leucovorin; Lung Neoplasms; Middle Aged; Nivolumab; Oxaliplatin; Prognosis; Radiosurgery

A 56-year-old woman was diagnosed with rectal cancer and liver metastases(Stage IV), and underwent low anterior resection and laparoscopic partial hepatectomy. The patient received adjuvant chemotherapy(mFOLFOX6 for 24 weeks), but developed multiple lung metastases 11 months later. Before undergoing a pulmonary resection, the patient presented with acute small bowel obstruction. Abdominal computed tomography showed small bowel stenosis due to a tumor, and we suspected peritoneal metastases from the rectal tumor. We performed partial resection of the small intestine, and histopathological examination revealed a primary small bowel tumor. The patient was discharged to her home without complications, and later underwent pulmonary resections for bilateral lung metastases. We usually suspect that small bowel obstruction is due to peritoneal metastases in patients with advanced colorectal tumors, but must consider the rare possibility of a separate primary small bowel tumor, especially in patients with a solitary lesion. We report a rare primary small bowel tumor after FOLFOX treatment in a patient with Stage IV rectal cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Intestinal Neoplasms; Intestine, Small; Leucovorin; Liver Neoplasms; Lung Neoplasms; Middle Aged; Neoplasms, Multiple Primary; Organoplatinum Compounds; Rectal Neoplasms

Controversy exists regarding the safety of agents that systemically inhibit epidermal growth factor receptor (EGFRi) in oncologic patients in terms of toxicity to the ocular surface. We performed a prospective clinical study comparing the ocular surface toxicity of systemic EGFRi between a case and a control group.. Patients with lung or colon cancer were divided in two groups: 25 patients treated with systemic EGFRi and 25 control patients without EGFRi treatment. Patients in both groups were chemotherapy naive. Four visits were scheduled in a one year period comparing signs and symptoms in terms of symptom questionnaires (SIDEQ, OSDI and AVS), corneal fluorescein staining (Oxford test), tear production (Schirmer's test) and a quantitative evaluation of conjunctival chemosis and hyperemia. Basal epithelial cell density (CEBD) and corneal subepithelial nerve fiber density (CNFD) were measured and compared using confocal microscopy (Heidelberg Engineering, Germany). The differences in each variable were compared with the analysis of variance (ANOVA). A P value<0.05 was considered significant for all comparisons.. No statistically significant differences were found between patients under EGFRi treatment and the age-matched controls in the variables analyzed. When cases and controls were evaluated separately, the case group showed a significantly worse progression of signs (chemosis score, CFS, Schirmer's) as well as in terms of CEBD and CNFD (all P<0.05).. Systemic EGFRi may increase dry eye signs as well as decrease CEBD and CNFD. This study may help us to understand the true toxicity of EGFRi to the ocular surface.

Topics: Adenocarcinoma; Administration, Oral; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Case-Control Studies; Colorectal Neoplasms; Cornea; Dry Eye Syndromes; ErbB Receptors; Female; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Prospective Studies; Protein Kinase Inhibitors

Clinical trials demonstrated that 6-37% of the patients with colorectal liver-limited metastases underwent surgical resection after first-line chemotherapy. However, limited information is available on the conversion of colorectal cancer patients with lung metastases to resection by systemic chemotherapy.. We retrospectively investigated 156 patients with unresectable colorectal cancer who received oxaliplatin- or irinotecan-based first-line systemic chemotherapy with or without antibodies in our department between January 2007 and December 2015. The conversion rate to surgery and chemotherapeutic regimens and periods were analyzed with respect to the target organ.. In addition to 4 patients who achieved complete response, 73 exhibited tumor shrinkage of any extent. Twenty patients underwent secondary surgery, all of whom received targeting antibodies. In 75 patients with liver metastases, 18 (24%) were converted to resection after chemotherapy for a median of 110 days. In contrast, 4 (7%) out of 56 patients with lung metastases underwent resection after chemotherapy for a median of 449 days. Conversion was an independent prognostic factor in patients with lung metastases.. The conversion rate to resection was lower for colorectal cancer patients with lung metastasis by systemic chemotherapy, which required a longer duration than for those with liver metastases.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Colorectal Neoplasms; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Lung Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Prognosis; Retrospective Studies

Cetuximab combined with chemotherapy is one of the first-line treatments of metastatic colorectal cancer. Although disease progression inevitably occurs, rechallenge and maintenance therapies using cetuximab-based regimens may be beneficial, particularly for patients with wild-type (WT) KRAS.. A 47-year-old female patient who underwent right hemicolectomy presented with an ulcerative adenocarcinoma (grade 2) revealed by histopathological analysis. The patient received three cycles of adjuvant chemotherapy, but disease recurred 15 months later. Cetuximab and a FOLFOX-4 regimen were administered, followed by surgery and adjuvant chemotherapy that was administered for approximately one year. Three years after completing adjuvant therapy, her serum carcinoembryonic antigen levels rapidly increased, and enhanced computed tomography showed widespread metastases. Rechallenge with cetuximab and the FOLFIRI regimen was then initiated, and after 12 cycles, lesions in the lung and liver shrank significantly, and serum CEA levels dramatically declined. Maintenance therapy with cetuximab and capecitabine was then administered for 10 months until the metastatic lesions in the lung and liver enlarged.. Rechallenge and maintenance therapy with cetuximab-based chemotherapy were relatively effective for managing a female patient with WT KRAS. Optimization of this strategy requires further in-depth investigations of more patients.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoembryonic Antigen; Cetuximab; Colorectal Neoplasms; Fatal Outcome; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Maintenance Chemotherapy; Middle Aged; Organoplatinum Compounds; Treatment Outcome

To analyze the outcome of patients with ampullary cancer who had undergone curative surgery followed by adjuvant chemoradiotherapy and to identify the prognostic factors for these patients. : Between January 1991 and August 2006, 71 patients with ampullary cancer underwent curative resection followed by adjuvant radiotherapy. There were 38 males and 33 females, and median age was 56 years (range, 28 to 77 y). Postoperative radiotherapy was delivered to tumor bed and regional lymph nodes up to 40 to 50 Gy at 2 Gy/fraction; 67 patients also received intravenous 5-fluorouracil as a radiosensitizer. Median follow-up duration was 72 months for survivors.. There were 5 isolated locoregional recurrences, 20 isolated distant metastases, and 11 combined locoregional and distant relapses. The 5-year locoregional relapse-free and overall survival rates were 76.2% and 64.5%, respectively. On multivariate analysis, nodal ratio and histologic differentiation were significant prognostic factors for overall survival (P=0.0382 and 0.0331, respectively).. Adjuvant chemoradiotherapy after curative resection can achieve a long-term survival rate in patients with ampullary cancer. Nodal ratio and histologic differentiation are independent prognostic factors for these patients.

Topics: Adult; Aged; Ampulla of Vater; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Common Bile Duct Neoplasms; Disease-Free Survival; Dose Fractionation, Radiation; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Mitomycin; Neoplasm Recurrence, Local; Pancreaticoduodenectomy; Retrospective Studies; Survival Rate; Tegafur; Treatment Failure

The aim of this retrospective study was to analyse the efficacy of gemcitabine-oxaliplatin (gemox) or 5-fluorouracil-oxaliplatin (folfox) in the treatment of metastatic pulmonary carcinoid tumors.. 45 patients were included in two tertiary referral centers between January 1999 and January 2013. Typical, atypical carcinoids or not otherwise specified carcinoids were diagnosed according to WHO criteria in 19%, 57%, and 24% of cases by two expert pathologists. Patients had synchronous (38%) or metachronous (62%) metastastic disease (median of 2 (1-5) metastatic sites). Seventy-nine percent had progressive disease before start of chemotherapy. Treatment consisted of: gemcitabine 1000mg/m(2) and oxaliplatin 100mg/m(2) every 2 weeks (gemox regimen, n=24) or 5-fluorouracil (5-FU) (400mg/m(2) in bolus injection and 5-FU 2400mg/m(2) in 46h-infusion) and oxaliplatin 85mg/m(2) (folfox regimen, n=21) every 2 weeks. Tumor response was assessed according to RECIST criteria every 8-12 weeks. Progression free survival and overall survival were assessed using Kaplan Meier curves.. Patients received oxaliplatin-based chemotherapy in first-line (20%), second-line (33%), or post-second-line (47%) systemic treatment. The median number of cycles was 8 (1-12). Nine (20%) stopped oxaliplatin before 8 cycles because of toxicity. Nine patients (20%) had a partial response and 29 (64%) had stable disease. Median progression free survival (PFS) was 15 (6-25) months. Median overall survival (OS) was 34 (21-49) months. No significant difference was observed in response and PFS between either regimens.. Our results suggest that either gemcitabine-oxaliplatin or 5-fluorouracil-oxaliplatin combinations are attractive chemotherapy regimen in metastatic pulmonary carcinoid tumors.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoid Tumor; Deoxycytidine; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Retrospective Studies; Treatment Outcome

We report an 84-year-old woman with multiple lung metastases from sigmoid colon cancer successfully treated with an oral combination chemotherapeutic agent regimen(UFT/LV).The patient had undergone colectomy for sigmoid colon cancer. Histological examination confirmed a pT4a, pN3, pM1a(LYM), pStage IV tumor.The patient refused adjuvant chemotherapy. However, approximately 9 months postoperatively, she developed a severe cough.Chest radiography and computed tomography(CT)revealed multiple progressive lung metastases.Thereafter, considering her advanced age and general condition, an oral UFT/LV regimen(UFT 300mg/LV 75mg for 7 days every 14 days)was initiated.Two and a half months after initiating chemotherapy, symptom amelioration was observed.Chest radiography and CT showed disappearance of several of the lung metastases, indicating a Partial Response(PR).For the nearly one year to date since diagnosis, she has remained free of cough and the PR has been maintained without chemotherapy-associated adverse events.She is currently being managed on an outpatient basis.The oral UFT/LV regimen is considered to be among the potentially effective and safe treatments for elderly patients with postoperative metastases from colon cancer.

Topics: Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Colectomy; Female; Humans; Leucovorin; Lung Neoplasms; Sigmoid Neoplasms; Tegafur; Treatment Outcome; Uracil

We present the case of a 43-year-old-man with wild-type KRAS and BRAF colorectal adenocarcinoma that was metastatic to the liver and lung. The patient initially received neoadjuvant chemotherapy with FOLFOX and bevacizumab, followed by surgical resection of the primary tumor and hepatic metastases. His disease recurred shortly after surgery and he was treated with FOLFIRI plus the anti-EGFR antibody cetuximab. After this regimen failed to arrest his disease progression, treatment with FOLFIRI in combination with another anti-EGFR antibody, panitumumab was started. While on this therapy, the patient's lung nodules remained largely stable but metastatic lesions within the liver continued to progress. Our case highlights the differences between panitumumab and cetuximab, and contemplates the possible explanations for this patient's apparently heterogeneous disease progression within the liver despite stabilization of multiple pulmonary nodules.

Topics: Adenocarcinoma; Adult; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cetuximab; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Neoplasm Metastasis; Neoplasm Recurrence, Local; Organoplatinum Compounds; Panitumumab

In recent decades, the management of rectal cancer has been significantly improved by optimizing the surgical treatment with the total mesorectal excision and the development of neoadjuvant radiotherapy with or without chemotherapy. In this study, we investigated the impact of changes in practice over a period of 15 years in an expert centre.. A monocentric study was conducted retrospectively on cT3-resectable T4 patients who received chemoradiotherapy for a locally advanced rectal adenocarcinoma between 1993 and 2008. We studied sphincter preservation, pathological complete response (ypT0), survival, and toxicities by different concomitant chemotherapy and treatment period.. Among the 179 patients who had a chemoradiotherapy, 56.4% were received concomitant 5-fluoro-uracil-leucovorin, 28.5% with concomitant capecitabine, and 15.1% with concomitant oxaliplatin and capecitabine. The average dose of radiotherapy was 45 Gy (25×1.8 Gy). Five-year disease-free survival was 74.3% and overall survival 68.8%. The rate of local recurrence and distant metastases were 6.1 and 23.6%. In multivariate analysis, concomitant chemotherapy oxaliplatin and capecitabine improved the pathological complete response rate (ypT0; capecitabine: 6%, 5-fluoro-uracil-leucovorin: 10.3%, capecitabine-oxaliplatin: 22.2%), but not significantly (P=0.12) and with more toxicities, and treatment interruptions. Sphincter preservation rate was not improved significantly during the study period (1993-2004 vs. 2005-2008), but disease-free survival improved from 72.2% up to 87.5% (P=0.03).. Our results are consistent with those published in the literature. Concomitant chemotherapy with 5-fluoro-uracil or capecitabine remains the standard scheme. Upfront chemotherapy, before chemoradiotherapy, should be investigated with regard to the predominance of metastasis.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Anal Canal; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemoradiotherapy, Adjuvant; Deoxycytidine; Disease-Free Survival; Female; Fluorouracil; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Neoplasms, Second Primary; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms; Retrospective Studies; Treatment Outcome

The aim of the present retrospective study was to analyze clinical outcome and risk factors associated with treatment outcomes according to KRAS status in patient with metastatic colorectal cancer (mCRC) treated with bevacizumab (bev) plus chemotherapy in the first-line setting.. We performed observational study on 1622 patients with mCRC treated with bev plus oxaliplatin- or irinotecan-based chemotherapy, and correlated treatment outcomes with KRAS mutation status. The primary endpoint was progression-free survival (PFS) and additionally overall survival (OS). Adverse events of bevacizumab and risk factors including location of metastases were evaluated.. Mutation in KRAS was present in 40.6% of mCRC cases. The median PFS in patients with wild-type KRAS (wtKRAS) vs mutant KRAS was 11.5 vs 11.4 months, respectively. The median OS was 30.7 vs 28.4 months (p = 0.312). Patients with KRAS mutation had lung metastases more frequently than wtKRAS individuals (32.0% vs 23.8%; p = 0.001). We observed no difference in clinical outcome between hepatic and extrahepatic metastatic disease.. KRAS mutation does not interfere with clinical benefit from first-line treatment with bevacizumab plus chemotherapy in mCRC patients.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Capecitabine; Colorectal Neoplasms; Deoxycytidine; Disease-Free Survival; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Mutation; Organoplatinum Compounds; Oxaliplatin; Oxaloacetates; Proto-Oncogene Proteins; Proto-Oncogene Proteins p21(ras); ras Proteins; Retrospective Studies; Survival Rate; Young Adult

Stage III colon cancer is currently treated as an entity with a unified therapeutic principle. The aim of the retrospective study is to explore the clinicopathological characteristics and outcomes of site-specific stage III colon cancers and the influences of tumor location on prognosis.. Eight hundred ninety-five patients with stage III colon cancer treated with radical operation and subsequent adjuvant chemotherapy (5-fluorouracil/oxaliplatin) were divided into seven groups according to colon segment (cecum, ascending colon, hepatic flexure, transverse colon, splenic flexure, descending colon, and sigmoid colon). Expression of excision repair cross-complementing group 1 (ERCC1) and thymidylate synthase (TS) was examined by immunohistochemistry. We assessed if differences exist in patient characteristics and clinic outcomes between the seven groups.. There were significant differences in tumor differentiation (P < 0.001), T stage (P < 0.001), N stage (P < 0.001), American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) stage (P < 0.001), metachronous liver metastasis (P < 0.001), metachronous lung metastasis (P < 0.001), and ERCCI expression (P < 0.001) between the seven groups. Both 5-year recurrence-free survival (RFS) and 5-year overall survival (OS) exhibited significant differences (both P < 0.001) with survival gradually decreasing from cecum to sigmoid colon. Cox regression analyses identified that tumor location was an independent prognostic factor for RFS and OS.. Stage III colon cancer located proximally carried a poorer survival than that located distally. Different efficacies of FOLFOX adjuvant chemotherapy may be an important factor affecting survival of site-specific stage III colon cancers.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Cecal Neoplasms; Chemotherapy, Adjuvant; Colon; Colonic Neoplasms; Disease-Free Survival; DNA-Binding Proteins; Endonucleases; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasm Grading; Neoplasm Staging; Organoplatinum Compounds; Retrospective Studies; Survival Rate; Thymidylate Synthase

Topics: Angiogenesis Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colonic Neoplasms; Colonoscopy; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Middle Aged; Positron-Emission Tomography; Tomography, X-Ray Computed

We report a case of radical resection of rectal cancer with multiple liver and lung metastases after preoperative chemotherapy. A 54-year-old woman presented with abdominal pain and loss of body weight due to rectal cancer with multiple liver and lung metastases. Therefore, the patient received 14 courses of bevacizumab+mFOLFOX6, and 7 courses of panitumumab+FOLFIRI. After the chemotherapy, the size of the distant metastases reduced by 62% on computed tomography, according to RECIST. Due to the reduction in size, a conversion surgery was attempted. First, an abdominal operation with laparoscopy was performed, and 2 months later an operation to resect the lung metastases via thoracoscopy was performed. Currently, 3 months after surgery, the patient is alive, without recurrence.

Topics: Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Middle Aged; Organoplatinum Compounds; Panitumumab; Rectal Neoplasms

The SCAN colorectal cancer systemic therapy workgroup aimed to develop Singapore Cancer Network (SCAN) clinical practice guidelines for systemic therapy for colorectal cancer in Singapore.. The workgroup utilised a modified ADAPTE process to calibrate high quality international evidence-based clinical practice guidelines to our local setting.. Five international guidelines were evaluated-those developed by the National Comprehensive Cancer Network for colon (2014) and rectal (2014) cancer, the European Society of Medical Oncology for advanced (2012) and early (2013) cancer and the National Institute of Clinical Excellence (2011). Recommendations on systemic therapy in colorectal cancer were produced.. These adapted guidelines form the SCAN Guidelines 2015 for systemic therapy of colorectal cancer.

Topics: Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Capecitabine; Cetuximab; Chemotherapy, Adjuvant; Colectomy; Colorectal Neoplasms; Fluorouracil; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Metastasectomy; Microsatellite Instability; Organoplatinum Compounds; Oxaliplatin; Panitumumab; Singapore

A patient in his 70s was diagnosed with rectal cancer (pT3, pN1, cM0, and pStage IIIa) for which he underwent low anterior resection of the rectum and received adjuvant therapy with UFT/LV. Multiple liver, lung, and para-aortic lymph node metastases were detected after 6 months, and the patient then received a total of 24 courses of FOLFOX4 plus bevacizumab instead of UFT/LV. The liver and para-aortic lymph node metastases showed a complete response (CR), and the lung metastases markedly diminished. Therefore, the patient completed the FOLFOX4 plus bevacizumab chemotherapy regimen. After 2 years, a recurrence of the initial liver metastases was detected. A CR on radiological imaging does not correspond to a pathological CR. Therefore, a careful follow-upis required even when a CR on radiological imaging is achieved.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Aorta; Bevacizumab; Chemotherapy, Adjuvant; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Organoplatinum Compounds; Rectal Neoplasms; Recurrence

Colorectal cancer is the fourth most common cancer diagnosed in the United States, and the third most common cause of death from cancer. Approximately 20% of the patients with colorectal cancer have distant metastasis during diagnosis. Primary tumor resection is controversial in unresectable metastatic colorectal cancer (CRC). We studied the survival effect of primary tumor resection in unresectable metastatic CRC according to kirsten ras (KRAS) mutation status.. Seventy eight CRC cases with unresectable metastasis were included in the study. The KRAS status was known in all patients. 34 patients had undergone primary tumor resection before 1st chemotherapy.. ThE median time from primary tumor resection to first chemotherapy was 6 (3-17) weeks. The survival was better in the unresectable metastatic colon patients with resected primary tumor, but it was statistically non-significant (P = 0.07). The median OS was similar (P = 0.91) in the KRAS wild patients with or without primary tumor resection. The median OS was 28 months in KRAS mutant patients with primary tumor resection, 14 months in KRAS mutant patients without primary tumor resection (P = 0.002).. Primary tumor resection offers survival advantage in KRAS mutant patients, but randomized prospective studies are required.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Cetuximab; Cohort Studies; Colectomy; Colorectal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Mutation; Organoplatinum Compounds; Prognosis; Proto-Oncogene Proteins p21(ras); Retrospective Studies; Survival Rate

We aimed to investigate the efficacy of second line treatment with modified FOLFOX6 (mFOLFOX6) following cisplatin- plus 5-fluorourasil (CF) chemotherapy in patients with metastatic esophagus cancer (mEC).. In our oncology clinic, between March 2011 and September 2014, we reviewed patients admitted with progressive mEC following first line CF chemotherapy and those with >60 kanofsky performance status performed second line mFOLFOX6 regimen.. A total of 242 patients with mEC were evaluated. 94 of 242 patients (38.8%) had received second-line chemotherapy treatment. All of these patients had received mFOLFOX6 regime. Median age was 53 years (range: 28-71). The received median number of chemotherapy cycles was 6 (2-12). Objective response rate (ORR) was obtained in 39 of 94 (41.4%) patients, 6 (6.3%) of these had complete response (CR) and 33 (35.1%) had partial response (PR). Stable disease (SD) was obtained in 20 (21.3%) patients and progression was observed in 35 (37.3%) patients. Grade ¾ toxicity was observed in 67 (71.2%) patients. The hematologic toxicity was found as the most common toxicity (69.1%).. mFOLFOX6 regimen as a second line treatment can be applied to the mEC patients with progressive disease following CF chemotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Carcinoma, Squamous Cell; Cohort Studies; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymph Nodes; Male; Middle Aged; Organoplatinum Compounds; Retrospective Studies; Treatment Outcome

We previously reported that the host response to certain chemotherapies can induce primary tumor regrowth, angiogenesis, and even metastases in mice, but the possible impact of anti-VEGF-A therapy in this context has not been fully explored. We, therefore, used combinations of anti-VEGF-A with chemotherapy on various tumor models in mice, including primary tumors, experimental lung metastases, and spontaneous lung metastases of 4T1-breast and CT26-colon murine cancer cell lines. Our results show that a combined treatment with anti-VEGF-A and folinic acid/5-fluorouracil/oxaliplatin (FOLFOX) but not with anti-VEGF-A and gemcitabine/cisplatinum (Gem/CDDP) enhances the treatment outcome partly due to reduced angiogenesis, in both primary tumors and experimental lung metastases models. However, neither treatment group exhibited an improved treatment outcome in the spontaneous lung metastases model, nor were changes in endothelial cell numbers found at metastatic sites. As chemotherapy has recently been shown to induce tumor cell invasion, we tested the invasion properties of tumor cells when exposed to plasma from FOLFOX-treated mice or patients with cancer. While plasma from FOLFOX-treated mice or patients induced invasion properties of tumor cells, the combination of anti-VEGF-A and FOLFOX abrogated these effects, despite the reduced plasma VEGF-A levels detected in FOLFOX-treated mice. These results suggest that the therapeutic impact of antiangiogenic drugs varies in different tumor models, and that anti-VEGF-A therapy can block the invasion properties of tumor cells in response to chemotherapy. These results may implicate an additional therapeutic role for anti-VEGF-A when combined with chemotherapy.

Topics: Angiogenesis Inhibitors; Animals; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Fluorouracil; Humans; Immunotherapy; Leucovorin; Lung Neoplasms; Mice; Neoplasm Transplantation; Neoplasms, Experimental; Neovascularization, Pathologic; Organoplatinum Compounds; Vascular Endothelial Growth Factor A

Stereotactic radiotherapy is a minimally invasive technique for delivering highly focused ionizing radiation with extreme precision. This technique was initially developed in neurosurgical practice and applied to extracranial lesions in the 1990s, and was termed stereotactic body radiotherapy (SBRT). Studies have reported that the resection of distant metastases from colorectal cancer (CRC) contributes to relatively long-term survival. However, the resection of pulmonary and liver metastases is not possible for various reasons. SBRT offers a therapeutic alternative to unresectable metastatic lesions. The present study describes three cases of distant metastasis from CRC that exhibited a complete response (CR) to SBRT. Case 1 is a 70-year-old man with recurrent liver metastases after surgery for rectal cancer with liver metastasis (S3: diameter 1.8 cm and volume 3.0 ml; S6: diameter 1.3 cm and volume 1.2 ml). Cases 2 and 3 were 65-year-old and 70-year-old men, respectively. Both patients had pulmonary metastasis after surgery for rectal and cecum cancer (Case 2: diameter 1.2 cm and volume 0.9 ml; Case 3: diameter 0.8 cm and volume 0.27 ml). All cases were moderately differentiated adenocarcinomas. No serious adverse side-effects were observed during the therapy. CR was obtained in all patients on the basis of computed tomography 15-33 months after radiotherapy. Our experience supports that SBRT is a safe and alternative technique for resection in patients with distant metastasis from CRC who have small metastatic tumor volume.

Topics: Adenocarcinoma; Aged; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Organoplatinum Compounds; Radiosurgery; Treatment Outcome

Weekly cetuximab plus irinotecan-based regiments are standard first- and second-line chemotherapy for patients with KRAS wild-type metastatic colorectal cancer (mCRC). However, the chemotherapy regimens are given every 2 weeks, which is asynchronous with cetuximab weekly administration. This study investigated the efficacy and safety of biweekly cetuximab administration in patients with mCRC. Twenty-six patients with KRAS wild-type mCRC, who received biweekly cetuximab plus FOLFIRI/irinotecan as first/second-line chemotherapy, at least three cycles of cetuximab and once CT evaluation in West China Hospital from May 2010 to February 2013, were retrospectively analyzed. The median number of cetuximab administrations was 8.3 (range 3-20). Fourteen patients received FOLFIRI as first-line therapy; response rate was 50.0%; median PFS was 8.8 months (95% CI 4.9-12.7). Ten patients received FOLFIRI and two patients received irinotecan as second-line therapy; response rate was 33.3%; median PFS was 4.6 months (95% CI 0.9-8.3). The toxicity was similar to weekly cetuximab combination schedules. Rash was observed in 69.2% of evaluable patients (grade 3 in 7.7%). Overall, our results show that biweekly cetuximab plus FOLFIRI/irinotecan may be as effective and safe as the standard weekly schedule.

Topics: Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Asian People; Camptothecin; Cetuximab; Colorectal Neoplasms; Female; Fluorouracil; Follow-Up Studies; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Prognosis; Proto-Oncogene Proteins; Proto-Oncogene Proteins p21(ras); ras Proteins; Retrospective Studies; Salvage Therapy; Survival Rate

We aimed to investigate the efficacy and tolerability of a FOLFOX7 regimen in the first-line treatment of metastatic colorectal cancer (mCRC) patients.. Patients were evaluated in two groups. Group A did not receive any treatment before, and group B had metastasectomy or metastasectomy plus primary tumor resection.. In total, 132 mCRC patients had received FOLFOX7 regimen. The A group consisted of 117 (88.6%) patients, and group B consisted of 15 (11.4%) patients. In the A group, 52.1% had an objective response, 9.4% complete response, 42.7% partial response, 24.8% stable response, and 23.1% progression, and there was a 54.5% rate of primary tumor resection, 22.2% rate of metastasectomy, 80.7% rate of R0 metastasectomy, 19.1% rate of R1 metastasectomy, 15 (10-19) months median progression-free survival, and 32 (22-41) months median overall survival. In the B group, 40 (4-70) months median disease-free survival and 58 (21-94) months median overall survival were found. When toxicities were evaluated, grade 3/4 toxicity was observed in 35.6%. Grade 3/4 hematologic toxicity was the most frequently observed toxicity (29.5%).. FOLFOX7 regimen was found to be an efficient and safe regimen for the first-line treatment of mCRC patients.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Metastasectomy; Middle Aged; Organoplatinum Compounds; Survival Rate; Treatment Outcome; Young Adult

Topics: Adenocarcinoma; Aged; Anemia; Antifibrinolytic Agents; Antineoplastic Combined Chemotherapy Protocols; Blood Coagulation; Carcinoma, Squamous Cell; Cecal Neoplasms; Disseminated Intravascular Coagulation; Fatal Outcome; Female; Fibrinogen; Fibrinolysis; Fluorouracil; Heart Diseases; Hemorrhage; Humans; Leucovorin; Lung Neoplasms; Lymphatic Metastasis; Multiple Organ Failure; Neoplasms, Multiple Primary; Organoplatinum Compounds; Postoperative Complications; Thrombosis; Tranexamic Acid; Vulvar Neoplasms

Colorectal cancer (CRC) is among the most common cancers worldwide, but marked epidemiological differences exist between Asian and non-Asian populations. Hence, a consensus meeting was held in Hong Kong in December 2012 to develop Asia-specific guidelines for the management of metastatic CRC (mCRC). A multidisciplinary expert panel, consisting of 23 participants from 10 Asian and 2 European countries, discussed current guidelines for colon or rectal cancer and developed recommendations for adapting these guidelines to Asian clinical practice. Participants agreed that mCRC management in Asia largely follows international guidelines, but they proposed a number of recommendations based on regional 'real-world' experience. In general, participants agreed that 5-fluorouracil (5-FU) infusion regimens in doublets can be substituted with UFT (capecitabine, tegafur-uracil) and S1 (tegafur, 5-chloro-2,4-dihydroxypyridine and oxonic acid), and that the monoclonal antibodies cetuximab and panitumumab are recommended for KRAS wild type tumors. For KRAS mutant tumors, bevacizumab is the preferred biological therapy. FOLFOX (folinic acid, 5-FU, and oxaliplatin) is preferred for initial therapy in Asian patients. The management of mCRC is evolving, and it must be emphasized that the recommendations presented here reflect current treatment practices and thus might change as more data become available.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Asia; Bevacizumab; Camptothecin; Capecitabine; Cetuximab; Colonic Neoplasms; Combined Modality Therapy; Deoxycytidine; Drug Combinations; ErbB Receptors; Fluorouracil; Guideline Adherence; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Magnetic Resonance Imaging; Metastasectomy; Neoplasm Staging; Organoplatinum Compounds; Oxaloacetates; Oxonic Acid; Panitumumab; Practice Guidelines as Topic; Proto-Oncogene Proteins; Proto-Oncogene Proteins p21(ras); ras Proteins; Rectal Neoplasms; Tegafur; Tomography, X-Ray Computed

XELOX plus bevacizumab (XELOX-Bev) and FOLFIRI plus Bevacizumab (FOLFIRI - Bev) treatments are an effective strategies patients with metastatic colorectal cancer (mCRC).The aim of this study was to compare efficacy of first-line XELOX-Bev treatment vs FOLFIRI-Bev treatment for mCRC.. A total of 409 patients with mCRC who received chemotherapy were included and divided into 2 groups. Group 1 (n=298) received XELOX-Bev and Group 2 (n=111) FOLFIRI-Bev. Comparisons were made in terms of overall (OS) and progression-free (PFS) survival, response rate (RR), and grade 3-4 toxicity.. Median follow-up was 11 months in Group 1 and 15 months for Group 2. Complete remission was observed in 29 (9.7%) and 2 (1.8%) patients, partial remission in 139 (46.6%) and 27 (24.5%) , stable disease in 88 (29.5%) and 49 (44.1%) and progressive disease in 42 (14.1%) and 33 (30.0%) patients in Group 1 and 2, respectively. Median OS was 25 months (range 2-57 months, 95%CI; 22.2-27.7) for Group 1 and 20 months (range 1-67 months, 95%CI; 16.8-23.1) for Group 2 (p=0.036). Median PFS was 9.6 months (range 2-36 months, 95%CI; 8.8-10.4) for Group 1 and 9 months (range 1-44 months, 95%CI; 7.4-10.5) for Group 2 (p=0.019). Objective RR was 56.4% in Group 1 and 26.1% in Group 2 (p<0.001).. First-line XELOX-Bev is more effective with a better response rate, prolongation of median PFS/OS, and a superior safety profile compared with FOLFIRI-Bev.

Topics: Adult; Aged; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Bone Neoplasms; Camptothecin; Capecitabine; Carcinoma; Colonic Neoplasms; Deoxycytidine; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Oxaloacetates; Retrospective Studies; Treatment Outcome

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

In this case report, the authors aim to demonstrate the success of recent methods in the radical treatment of a patient with primary inoperable liver and subsequent colorectal cancer pulmonary metastases.. A 75 year old patient with inoperable bulky metastasis in the right hepatic lobe and insufficient future remnant liver volume was indicated for a stage procedure in the liver parenchyma. Embolization of the right branch of the portal vein was first performed with subsequent administration of stem cells into the contralateral liver lobe. Following compensatory growth of the left liver lobe, right-sided hepatectomy was performed with subsequent adjuvant oncological treatment. Six months after the surgery, a metastasis developed in the right pulmonary lobe which was solved by metastasectomy.. The patient, one year after the diagnosis of inoperable liver metastasis, is completely healthy and free of signs of disease recurrence.. A comprehensive oncosurgical approach using up-to-date diagnostic and treatment options may offer patients with metastatic colorectal cancer, radical treatment with the hope of long-term quality survival.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Embolization, Therapeutic; Fluorouracil; Hematopoietic Stem Cell Transplantation; Hepatectomy; Humans; Leucovorin; Liver Neoplasms; Liver Regeneration; Lung Neoplasms; Male; Organoplatinum Compounds; Pneumonectomy

Efficacy of chemotherapy plus bevacizumab has been shown in patients with metastatic colorectal cancer (mCRC) compared with chemotherapy alone. The aim of the present study was to evaluate the efficacy and safety of FOLFIRI or XELIRI regimens in combination with bevacizumab for mCRC patients in a first-line setting.. A total of 132 patients with previously untreated and histologically confirmed mCRC were included. They were treated with either FOLFIRI-Bevacizumab (Bev) or XELIRI-Bev according to physician preference. The efficacy and safety of the two regimens were compared.. Between 2006 and 2010, 68 patients were treated with the XELIRI-Bev regimen, while the remaining 64 patients received the FOLFIRI-Bev regimen. The median age was 58.5 years (53.6 years in the FOLFIRI-Bev and 59.7 years in the XELIRI-Bev arm, p=0.01). Objective response rate was 51.6% for FOLFIRI-Bev versus 41.2% for XELIRI-Bev (p=0.38). At the median follow-up of 24.5 months, the median progression-free survival (PFS) was not different between two groups (14.2 months in FOLFIRI-Bev vs. not reached in the XELIRI-Bev, p=0.30). However, median overall survival time for the FOLFIRI-Bev arm was better than that for patients treated with XELIRI- Bev, but these differences was not statistically significant (37.8 months vs. 28.7 months, respectively, p=0.58). Most commonly reported grade 3-4 toxicities (FOLFIRI-Bev vs XELIRI-Bev) were nausea/vomiting (7.8% vs. 14.7%, p=0.27), diarrhea (10.9% vs 22.1%, p=0.10), hand-foot syndrome (0% vs 8.8%, p=0.02) and neutropenia (18.7% vs 27.9%, p=0.22).. Our results showed that FOLFIRI-Bev and XELIRI-Bev regimens were similarly effective treatments in a first-line setting for patients with untreated mCRC, with manageable adverse event profiles.

Topics: Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Capecitabine; Colorectal Neoplasms; Deoxycytidine; Female; Fluorouracil; Follow-Up Studies; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Prognosis; Retrospective Studies; Survival Rate; Young Adult

Marginal statistical evidence of efficacy of adjuvant and/or perioperative chemotherapy after resection of colorectal metastases exists, but formal recommendations are still lacking. The present study evaluated the adjuvant systemic chemotherapy after the first resection of liver and lung colorectal cancer metastases.. We retrospectively reviewed data of 181 consecutive unselected patients with R0 resection of colorectal metastases treated simultaneously at 2 institutions from 1997 to 2004. Patients > 75 years old, with an Eastern Cooperative Oncology Group Performance Status Score ≥ 2 or unfit for adjuvant chemotherapy were excluded from the analysis. The decision on chemotherapy after surgery was left to the patient in the absence of conclusive data on the efficacy of adjuvant chemotherapy in this setting. A total of 151 patients (131 with liver metastases, 20 with lung metastases), 78 of whom underwent adjuvant chemotherapy, were evaluable for disease-free survival (DFS) and overall survival. The main prognostic factors for DFS after resection of colorectal cancer metastases were investigated in univariate and multivariate analyses.. At the univariate analysis, the number of resected lesions, lesion volume, disease-free interval and adjuvant systemic chemotherapy were the only significant prognostic factors. At multivariate analysis, only adjuvant chemotherapy and disease-free interval were independent prognostic factors (hazard ratios 1.66 and 1.62, respectively). The median DFS of patients who underwent systemic adjuvant chemotherapy was 16 months compared with 9.7 months for patients with observation alone (hazard ratio 1.56). Estimated 5-year DFS was 17.4% and 10.5% for treated and untreated patients, respectively.. Adjuvant chemotherapy after metastasectomy in patients with colorectal cancer showed a significant benefit for DFS.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Capecitabine; Chemotherapy, Adjuvant; Colorectal Neoplasms; Combined Modality Therapy; Deoxycytidine; Female; Fluorouracil; Follow-Up Studies; Hepatectomy; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Metastasectomy; Middle Aged; Neoplasm Staging; Prognosis; Retrospective Studies; Survival Rate

We report a case of advanced rectal cancer treated with chemotherapy, for which laparoscopic splenectomy had been effective for thrombocytopenia. A 56-year-old man suffered from advanced rectal cancer with multiple lung metastases. He underwent Hartmann's procedure and received chemotherapy with FOLFOX and FOLFIRI with bevacizumab. After 3 years and 2 months, he also suffered from splenomegaly and thrombocytopenia. Laparoscopic splenectomy produced and increased the thrombocyte count, allowing for a restart of chemotherapy. Oxaliplatin-based chemotherapy might produce hepatic sinusoid injury and induce splenomegaly owing to portal hypertension. Laparoscopic splenectomy seemed to be useful for treating thrombocytopenia, and allowed the continuation of chemotherapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Fatal Outcome; Fluorouracil; Humans; Laparoscopy; Leucovorin; Lung Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms; Splenectomy; Splenomegaly; Thrombocytopenia

To assess the efficacy and safety of bevacizumab (BEV) plus chemotherapeutic agents in the treatment of metastatic colorectal cancer (mCRC).. Seventy-seven mCRC patients received BEV plus 5-Fu type, oxaliplatin or irinotecan-based chemotherapy. The clinical efficacy and bevacizumab-related adverse reactions were observed. The efficacy assessment was conducted after at least 2 cycles of BEV therapy. The adverse reactions were recorded in each therapy cycle. Among the 77 cases, 64 patients had finished the efficacy assessment. The adverse reactions in all patients were assessed.. The overall response rate (ORR) of BEV plus chemotherapy regimen was 18.75% (12/64), and the disease control rate (DCR) was 75.0% (48/64). In 27 patients who received the regimen as first-line treatment, the ORR reached 37.0% (10/27), while the DCR was 85.2%. Four patients with potentially resectable lesions became resectable after the regimen and received R0 resection of the liver metastases successfully. Twenty-five patients who received the regimen as second line therapy had poor result with ORR 8.0% and DCR 76.0%. Hypertension was observed in 12 cases, with 8 cases of grade 1, 3 cases of grade 2, 1 case of grade 3. Various bleedings occurred in 24/77 cases (31.2%), all were of grade 1-2, including 17 cases of epistaxis, grade 1 hemorrhoid bleeding in one case, hematuria in 3 case (2 of grade 1, 1 of grade 2), GI bleeding in 2 cases, hemoptysis in 1 case (grade 2), and proteinuria in 4 cases (grade 1). Intestinal perforation occurred in 1 case (0.3%). In two patients who had incomplete intestinal obstruction history appeared exacerbated intestinal obstruction symptoms after the application of BEV plus CPT11 regimen.. BEV plus chemotherapy regimen as first-line treatment can improve the ORR and DCR of mCRC patients. When it was used as second- or later-line therapy, it may display satisfied DCR, although with a poor efficacy. The bevacizumab-related toxicity is mild and can be well tolerated.

Topics: Adult; Aged; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Capecitabine; Colonic Neoplasms; Deoxycytidine; Disease-Free Survival; Female; Fluorouracil; Follow-Up Studies; Hemorrhage; Humans; Hypertension; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaloacetates; Proteinuria; Rectal Neoplasms; Remission Induction; Young Adult

A 60-year-old woman was diagnosed as having duodenal cancer by upper gastrointestinal endoscopy and biopsy. Pylorus-preserving pancreatoduodenectomy was performed. Pathological findings suggested T4(CBD)N1M0 primary duodenal carcinoma. Adjuvant chemotherapy with S-1(80 mg/m² of S-1 administered for 2 weeks followed by a 1-week drug-free period)was administered after surgery. One year after the surgery, computed tomography(CT)scans showed swelling of the paraaortic lymph nodes. Recurrence of the duodenal carcinoma was diagnosed, and gemcitabine chemotherapy was initiated. Eight months later, CT scans revealed lung metastasis. The patient was then treated with oxaliplatin in combination with infusional 5-fluorouracil/Leucovorin(FOLFOX regimen). After completing 6 courses of the chemotherapy regimen, CT scans showed a partial response(PR). Currently, at 1 year, PR has been maintained. Therefore, we suggest that the FOLFOX regimen can be highly effective for the treatment of patients with duodenal carcinoma.

Topics: Antineoplastic Combined Chemotherapy Protocols; Duodenal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Lymphatic Metastasis; Middle Aged; Organoplatinum Compounds; Recurrence

To improve the prognosis of patients with urachal cancer and establish an effective chemotherapeutic regimen for distant metastases.. We conducted a retrospective study to evaluate the efficacy and safety of a modified combination of 5-fluorouracil, leucovorin and oxaliplatin (mFOLFOX6) therapy in patients with metastatic urachal cancer.. Five patients were treated with mFOLFOX6. Their median age was 65 years (range 41-80). The median follow-up time was 42 months (range 18-46). Two of the 5 patients (40%) showed an objective response: 1 achieved a clinically complete response and 1 a partial response. The grade 3/4 toxicity associated with this regimen was primarily neutropenia, but febrile neutropenia was not observed. Oxaliplatin treatment was discontinued because of a grade 2 allergic reaction in 1 patient. Grade 2 peripheral sensory neuropathy caused by oxaliplatin was observed in 2 patients, and the OPTIMOX (stop and go) approach had to be adopted.. mFOLFOX6 appears to be effective for the treatment of metastatic urachal cancer.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Retrospective Studies; Treatment Outcome; Urinary Bladder Neoplasms

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

Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Choriocarcinoma, Non-gestational; Chorionic Gonadotropin; Cyclophosphamide; Dactinomycin; Diagnostic Errors; Etoposide; False Positive Reactions; Female; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Pregnancy; Radiography; Treatment Outcome; Vincristine; Vitamin B Complex

A 61-year-old complaining of anorexia and general fatigue was admitted to our hospital for further examination. She was diagnosed as advanced sigmoid colon cancer with multiple metastases of lung, liver, and left hydronephrosis. Since curative surgery was not deemed possible, we started chemotherapy with bevacizumab/FOLFOX6 (bi-weekly drip infusion). After the 6th course, colonoscopy revealed a significant tumor reduction and changes to the scar tissues. CT did not reveal a complete disappearance, but found some reductions in metastases of lung and liver. Sigmoidectomy and lymph node resection (D1) were performed. We did not disappeared any dissemination and the histological diagnosis revealed a complete disappearance of cancer cells in the main tumor. She was discharged 13 days after surgery, following chemotherapy which included bevacizumab and XELOX. The chemotherapy using bevacizumab/FOLFOX6 is a candidate for the standard treatment strategy for inoperable advanced colon cancer. Herein we report this rare case with a review of the literature.

Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Female; Fluorouracil; Humans; Hydronephrosis; Leucovorin; Liver Neoplasms; Lung Neoplasms; Middle Aged; Organoplatinum Compounds; Sigmoid Neoplasms; Tomography, X-Ray Computed

We report a case of complete remission after treatment with tegafur-uracil (UFT)/Leucovorin (LV) therapy for pulumonary metastasis of rectal cancer. A 56-year-old male was admitted to our hospital with a diagnosis of rectal cancer (Ra, type2). Chest CT on admission demonstrated bilateral lung metastases (rt S2 and lt S4). After anterior resection of the primary tumor, oral UFT/LV was administered (UFT 400 mg/LV 75 mg, 4-week administration and 1-week no-administration period) on an outpatient basis. After 2 courses, chest CT revealed reduction of both metastases, and complete resection of the metastases by video assisted thoracic surgery (VATS) was planned. Pathological findings of a specimen revealed no residual cancer cells, indicating a complete response to UFT/LV therapy. After these treatments, combined therapy of UFT/LV was continued for 3 months, and the single administration of UFT was continued for 1 year. The patient experienced no adverse reactions, and has had no recurrent disease in 4 years. Oral UFT/LV therapy is considered to be a promising regimen for patients with resectable metastatic lesion from a standpoint of clinical efficacy and safety.

Topics: Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Rectal Neoplasms; Remission Induction; Tegafur; Tomography, X-Ray Computed; Uracil

Topics: Adenocarcinoma; Adult; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colorectal Neoplasms; Disease Progression; Fatal Outcome; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Organoplatinum Compounds; Tomography, X-Ray Computed; Uterine Perforation

Topics: Adjuvants, Immunologic; Administration, Metronomic; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Colonic Neoplasms; Deoxycytidine; Female; Fluorouracil; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Injections, Subcutaneous; Interleukin-2; Leucovorin; Lung Neoplasms; Lymphatic Metastasis; Maintenance Chemotherapy; Organoplatinum Compounds; Remission Induction; Sjogren's Syndrome; Treatment Outcome

Protein-bound polysaccharide K (PSK) has been used as a chemoimmunotherapy agent for the treatment of colorectal cancer. Recently, PSK was reported to be able to decrease some adverse effects of FOLFOX therapy, including neutropenia and peripheral neurotoxicity. Here, we report 2 patients with metastatic colorectal cancer, who unexpectedly were able to receive many courses of PSK+mFOLFOX6 therapy for a prolonged period. We speculate that FOLFOX therapy may achieve long-term tumor control with the aid of PSK without serious side effects for metastatic colorectal cancer patients.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Combined Modality Therapy; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Middle Aged; Organoplatinum Compounds; Polysaccharides; Time Factors

A 48-year-old man with respiratory discomfort was diagnosed with rectal cancer with carcinomatous lymphangiosis, together with lung and sternum metastasis. As the patient's performance status(PS) was 2, mFOLFOX6+bevacizumab (Bmab)therapy with a 20% reduction in the dose was started. Three courses of this treatment resulted in improved respiratory function, and his PS dropped to 1. A chest computed tomography(CT) scan taken after four courses of this treatment indicated that pleural effusion had almost disappeared, and that the shadow on the lung had also reduced. However, after 20 courses of this treatment the disease had progressed. The regimen was changed to irinotecan (CPT-11)+Bmab administration. All of these chemotherapeutic treatments were administered on an outpatient basis. Sixteen months after the diagnosis of rectal cancer, the patient died. In recent years, combination chemotherapy for unresectable colorectal cancer has become recognized as a standard regimen, though adverse effects frequently occur. Thus, intensive chemotherapy is not always recommended for patients with poor PS. In this report, we presented a case of pulmonary metastases from rectal cancer, carcinomatous lymphangiosis, and sternum metastasis that was successfully treated with mFOLFOX6+Bmab.

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

This case concerns a 50-year-old male patient who was diagnosed with rectal cancer without any obvious distal metastasis. The patient underwent abdominoperineal resection of the rectum with lateral lymph node dissection exclusively on the lesion side. An obturator lymph node metastasis was found, and histopathological tests revealed that the patient was in Stage IIIb. FOLFOX4 therapy was performed as postoperative adjuvant chemotherapy, and although temporary discontinuation was necessary due to abscesses in the buttocks, the patient completed 10 courses of chemotherapy. Lung metastasis was diagnosed when a chest computed tomography revealed a nodule 12 mm in diameter immediately above the diaphragm in the left S8. Since the nodule was a solitary tumor, radiofrequency ablation (RFA) therapy was performed, after which postoperative adjuvant chemotherapy was changed to FOLFIRI therapy. No obvious adverse events occurred, making it possible to continue the therapy without withdrawal. The lesions tended to gradually shrink, and during the 50th course of the therapy, the patient converted from partial remission (PR) to complete remission (CR). The FOLFIRI therapy was continued for another 6 months and then suspended for a while. The patient received 62 courses of FOLFIRI therapy in total. No sign of recurrence has been found. This case demonstrates the successful treatment and CR of recurrent lung metastasis after surgery for rectal cancer using lung RFA therapy and long-term administration of FOLFIRI.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Catheter Ablation; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Rectal Neoplasms; Recurrence; Time Factors

Resection + radiofrequency ablation (RFA) + hepatic artery infusion (HAI) + systemic chemotherapy for patients with unresectable synchronous liver-only metastases from colorectal cancer was rarely used previously.. We compared the outcomes of 42 patients underwent resection + RFA + HAI + systemic chemotherapy (RRHS) with that of 43 patients underwent resection + RFA + systemic chemotherapy (RRS).. The overall survival, the survival free of hepatic recurrence and the median survival in the RRHS group were all significantly higher than those in RRS group at 4 years. While the rates of adverse effects were similar in the two groups.. For patients with unresectable synchronous liver-only metastases from colorectal cancer, RRHS not only decreases but also postpones hepatic recurrence and therefore improves overall survival at 4 years, as compared with RRS.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Catheter Ablation; Colorectal Neoplasms; Combined Modality Therapy; Disease-Free Survival; Female; Fluorouracil; Hepatic Artery; Humans; Infusions, Intra-Arterial; Kaplan-Meier Estimate; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Proportional Hazards Models; Recurrence; Survival Rate; Treatment Outcome

Tolerability to irinotecan may be explained by pharmacogenomic polymorphisms. The purpose of this pharmacogenetic trial was to study the relevance of thymidylate synthase (TS) genotyping and of the isoform 1A1 of uridine diphosphate glucuronosyltransferase (UGT1A1) in order to tailor a combination chemotherapy regimen of 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) in metastatic colorectal cancer.. Patients with favourable TS and UGT1A1 profiles received high-dose (HD) FOLFIRI. Patients with TS-3R/3R could not receive HD-FOLFIRI, and those with UGT1A1-7/7 received standard FOLFIRI. The endpoints were overall response rate and safety.. Sixty-nine patients were enrolled in the study. Sixty-five patients received chemotherapy. Twenty patients (30.8%) achieved a partial response. The haematological toxicity was less in the HD-FOLFIRI subgroup. Patients having received HD-FOLFIRI did not experience increased levels of nausea-vomiting, asthenia or alopecia. Diarrhoea was more frequent with HD-FOLFIRI.. The genotypic assessment allowed a safer use of HD-FOLFIRI. Further investigations may target patients who benefit from intensification.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; DNA, Neoplasm; Female; Fluorouracil; Follow-Up Studies; Genotype; Glucuronosyltransferase; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Mutation; Neoplasm Staging; Pharmacogenetics; Pilot Projects; Polymerase Chain Reaction; Survival Rate; Thymidylate Synthase; Treatment Outcome; Young Adult

Oxaliplatin is an anticancer agent only approved for treatment of colorectal cancer, but that has shown some activity in metastatic breast cancer in phase II studies. Herein, we examine the off-label use of oxaliplatin in unselected patients with metastatic breast cancer.. A retrospective review was performed of all patients with metastatic breast cancer treated with oxaliplatin at our hospital between February 2003 and November 2009. Data concerning patterns of use, safety and activity were collected from patient charts.. The cohort comprised 30 female patients with a median age of 49 (range, 34-68 years) and a median of two involved organs (range, 1-4). All patients had been pretreated for metastatic breast cancer (median number of previous lines: 3; range:1-6). Oxaliplatin was only given in association either with fluorouracil and folinic acid (n=23) or with gemcitabine (n=7). The most commonly used dose was 100 mg/m(2) given every other week or every 3 weeks. As of December 15, 2009, the median duration of treatment was 4 (range, 0.75-11) months. Most of the discontinuations occured due to disease progression (n=11) and adverse effects or worsening condition (n=8). Twelve (40%) patients presented side-effects related to oxaliplatin use including hematotoxicity (n=8), gastrointestinal disorders (n=4) and neuropathies (n=2). Among patients evaluable for antitumoral activity (n=15), one patient achieved a complete response and one patient demonstrated a partial response. Most of the patients (57%) continued to be treated by chemotherapy after oxaliplatin. Median overall survival for the evaluable patients was 10 (range, 1-51) months.. In our population of heavily pretreated women with metastatic breast cancer, off-label use of oxaliplatin was of little worth. This off-label treatment was not the last therapeutic option for most of these patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Brain Neoplasms; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Cohort Studies; Deoxycytidine; Female; Fluorouracil; Gemcitabine; Humans; Leucovorin; Lung Neoplasms; Lymphatic Metastasis; Middle Aged; Neoplasm Staging; Off-Label Use; Organoplatinum Compounds; Oxaliplatin; Retrospective Studies; Skin Neoplasms; Survival Rate; Treatment Outcome

The antivascular endothelial growth factor monoclonal antibody bevacizumab with infusional 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) is a standard first-line treatment option for metastatic colorectal cancer. However, clinical data for capecitabine and irinotecan (XELIRI) with bevacizumab are limited.. A retrospective study was conducted on 139 patients with metastatic colorectal cancer to assess the efficacy and safety of first-line bevacizumab in combination with XELIRI or FOLFIRI. Primary endpoints were overall response rate (ORR), disease control rate and radical resection rate. Secondary endpoints included overall survival (OS), progression-free survival (PFS) and safety.. No significant differences in efficacy were observed between patients administered XELIRI or FOLFIRI with bevacizumab. The ORR, median OS and PFS and recorded adverse events (AEs) were comparable to those previously reported, with no new or unexpected AEs observed.. Bevacizumab is similarly efficacious and well tolerated when administered with XELIRI or FOLFIRI.

Topics: Adult; Aged; Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Capecitabine; Colorectal Neoplasms; Deoxycytidine; Disease Progression; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Retrospective Studies; Survival Rate; Treatment Outcome; Vascular Endothelial Growth Factor A

The patient was a 70-year-old male who had multiple lung metastases of rectal cancer. He was administered UFT(300mg/ day)and LV(75mg/day)after Hartmann operation for rectal cancer. He complained of fever and difficulty breathing after 2 courses of these medicines, and was admitted for UFT-and LV-induced interstitial pneumonitis. Treatment with methylpredni- solone(30mg/day)improved his symptoms and revealed radical findings. He was ready for discharge on the 10th day after treatment. Interstitial pneumonitis-induced UFT and LV is rare, but can lead to severe complications, which should be diagnosed and treated by corticosteroid as soon as possible.

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

Metastatic colorectal cancer has a low cure rate. When resection of metastases is feasible, however, survival is increased. We present a case of a patient with metastases that responded well to bevacizumab-containing treatment. Consequently, surgical resection of metastases was possible resulting in increased survival.

Topics: Adenocarcinoma; Adult; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colorectal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Organoplatinum Compounds; Treatment Outcome

Studies suggest that the continuous use of bevacizumab, a vascular endothelial growth factor inhibitor, may play a crucial role in improving therapy success in patients with metastatic colorectal cancer. This is a case report of a female 60-year-old patient with colon cancer metastases in the liver and lungs refractory to mFOLFOX6 and FOLFIRI given as first and second-line therapy, respectively, who demonstrated a good response to FOLFOXIRI and bevacizumab as third-line therapy. Bevacizumab may be added to first, second and third-line chemotherapy for palliative treatment of metastatic colorectal cancer, and data indicate an increase in patient survival with a good response rate and low toxicity.

Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colonic Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Middle Aged; Organoplatinum Compounds; Treatment Outcome

Topics: Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemoembolization, Therapeutic; Chemotherapy, Adjuvant; Colorectal Neoplasms; Deoxycytidine; Female; Fluorouracil; Hepatic Artery; Humans; Infusions, Intra-Arterial; Leucovorin; Liver Neoplasms; Lung Neoplasms; Magnetic Resonance Imaging; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Pelvic Exenteration; Positron-Emission Tomography; Proctocolectomy, Restorative; Quality of Life; Tomography, X-Ray Computed; Treatment Outcome

We describe the case of a 72-year-old woman with locally advanced lung tumor mimicking primary lung cancer. She was diagnosed with rectal cancer at the age of 65 years and was initially treated with platinum-based chemotherapy and thoracic irradiation as a treatment for primary lung cancer. One year later, a thyroid tumor was detected in her right thyroid lobe and was confirmed to have metastasized from rectal cancer based on pathological findings. Therefore, we suspected that she had metachronous double cancers and treated her with conventional chemotherapy for colorectal cancer. However, new life-threatening multiple lung metastases appeared. We treated her with the drug erlotinib because additional genetic analysis against primary lung tumor revealed typical double-activating epidermal growth factor receptor mutations. Histological review by immunostaining concluded that the primary lung tumor was composed of metastatic tumors from rectal cancer. In addition, genetic analysis revealed that the primary rectal cancer contained nearly the same types of double-activating epidermal growth factor receptor mutations as were present in the lung tumor. This is the first report of a case of rectal adenocarcinoma with double-activating epidermal growth factor receptor mutations.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Camptothecin; Colorectal Neoplasms; DNA Mutational Analysis; ErbB Receptors; Erlotinib Hydrochloride; Female; Fluorouracil; Humans; Immunohistochemistry; Leucovorin; Lung Neoplasms; Mutation; Neoplasms, Second Primary; Organoplatinum Compounds; Quinazolines; Thyroid Neoplasms; Transcriptional Activation; Treatment Failure; Treatment Outcome

An 82-year-old female was diagnosed with rectal cancer. Hartmann's procedure was performed and a curative resection was successfully achieved. Postoperative staging according to the classification of the Japanese Society for Cancer of the Colon and Rectum(The 7th Edition)was stage III. She received adjuvant chemotherapy after surgery with tegafur(UFT 300 mg/body/day)orally for 6 months. One year after the surgery, paraaortic lymph node metastasis and a local recurrence were diagnosed. She was treated with modified FOLFOX6 chemotherapy combined with bevacizumab. After 13 courses of treatment with FOLFOX6 and bevacizumab, multiple lung metastases were found. Therefore, we changed the chemotherapy regimens to FOLFIRI plus cetuximab. After 18 weeks of this new treatment she had two skin ulcerations around her stoma, a known side effect associated with cetuximab. We stopped cetuximab and continued chemotherapy with FOLFIRI alone. Seven weeks after cetuximab withdrawal, her skin ulcer healed with the support of a dermatologist and a wound ostomy continence nurse. We reintroduced cetuximab in a chemotherapy regimen with a reduced dose. After two infusions of cetuximab, skin ulceration recurred. We stopped cetuximab again and continued chemotherapy with FOLFIRI. Nine weeks later we resumed cetuximab, but this time the skin ulcer did not occur, and we were able to continue the chemotherapy regimen with FOLFIRI and cetuximab.

Topics: Aged, 80 and over; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cetuximab; Colorectal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Lymphatic Metastasis; Skin Ulcer; Tomography, X-Ray Computed

Cetuximab, a monoclonal antibody targeting epidermal growth factor receptor, has proven to be efficient in the treatment of metastatic colorectal cancer. We made a prospective study of the efficacy and toxicities of cetuximab-combination first-line (FOLFOX4) versus second/third-line (FOLFIRI) chemotherapy in 98 KRAS wild-type patients who had metastatic colorectal cancer. Wild-type KRAS had been identified by direct sequencing. Associations between clinical response/progression-free survival/overall survival/toxicities and cetuximab-combination chemotherapy timing were evaluated. The overall response rate was significantly higher for first-line treatment than for second/third-line treatment (relative risk = 1.707, 95% confidence interval = 1.121-2.598). Both progression-free survival and overall survival indicated significantly longer survival of first-line treatment than second/third-line treatment patients. This study is a validation of a molecular analysis of KRAS wild-type status for the prediction of response to cetuximab-combination chemotherapy for metastatic colorectal cancer patients; its predictive role was less prominent in the second/third-line than in the first-line treatment patients.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cetuximab; Colorectal Neoplasms; Disease-Free Survival; DNA Mutational Analysis; Drug Administration Routes; Drug Administration Schedule; Drug-Related Side Effects and Adverse Reactions; ErbB Receptors; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Mutation; Organoplatinum Compounds; Prospective Studies; Proto-Oncogene Proteins; Proto-Oncogene Proteins p21(ras); ras Proteins

This patient is a male in his 30's. He was diagnosed as hepatitis B virus-related huge primary liver cancer, 10cm in diameter, located in segment 4, accompanied with left portal thrombus and multiple lung metastases. Ten months after repeating systemic chemotherapy using gemcitabine (GEM)+carboplatin (CBDCA)+5-FU/leucovorin (LV) and hepatic arterial infusion chemotherapy with cisplatin (CDDP) 4 times, extended left lobectomy with caudate lobe could be successfully performed because of marked reducion of the huge tumor. The pathology revealed almost entirely necrotic changes of the main tumor, and the remaining, viable tumor nests showed combined hepatocellular and cholangiocarcinoma. Systemic chemotherapy was repeatedly given afterwards, which kept the pulmonary metastases stable without growth. The present case suggests that systemic chemotherapy using GEM+CBDCA+5-FU/LV may be useful in the multimodal treatment for the combined hepatocellular and cholangiocarcinoma with distant metastases.

Topics: Adult; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Carboplatin; Carcinoma, Hepatocellular; Cholangiocarcinoma; Cisplatin; Combined Modality Therapy; Deoxycytidine; Fluorouracil; Gemcitabine; Hepatic Artery; Humans; Infusions, Intra-Arterial; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male

We describe the case of a 74-year-old man with liver resection for originally unresectable liver metastasis from colorectal cancer after multiagent chemotherapy. Eleven bilobar liver metastases appeared four months after curative resection for double cancer of sigmoid colon and upper rectum. After 6 courses of multiagent chemotherapy (mFOLFOX 6 with bevacizumab), the number of liver metastasis decreased from 11 to 5. The patient underwent curative resection for liver metastasis. A new lesion of 7 mm in the segment 6 appeared 8 months after an initial liver resection. After 3 months' observation, two more liver metastases appeared. All liver metastases were resected. Solitary lung metastasis appeared 10 months after the second liver resection. The lung metastasis was also resected. The patient was alive with no evidence of disease in 33 months after the initial liver resection. We experienced the case with repeated liver resections after multiagent chemotherapy for originally unresectable bilobar liver metastasis. The therapeutic strategy which combines surgical resection with cytotoxic chemotherapy will be important more than ever.

Topics: Aged; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Combined Modality Therapy; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Neoplasm Staging; Neoplasms, Multiple Primary; Organoplatinum Compounds; Rectal Neoplasms; Sigmoid Neoplasms

A 69-year-old male was operated on sigmoidectomy for sigmoid colon cancer (SS, N2, H0, P0, M0, stage IIIb) 7 years ago. Two years later, he was diagnosed for rectal cancer and bilateral lung metastases by TBLB. We performed Mile's operation, and the rectal focus was pathologically diagnosed with a recurrence of sigmoid colon cancer. After surgery, chemotherapy with FOLFOX was started for bilateral lung metastases, resulting in CR during the 22 months. But bilateral lung metastases were exacerbated, and then we administered several other chemotherapies. Five years have passed since chemotherapy started, although the focuses tended to progress. Right now, he has been a chemotherapy outpatient for last 5 years.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Organoplatinum Compounds; Rectal Neoplasms; Recurrence; Sigmoid Neoplasms; Time Factors; Tomography, X-Ray Computed

A 54-year-old female with cecal cancer underwent Rt. hemicolectomy in December 2000. The lesion was mod, ss, p1(+), n1, stage IV. The level of CEA increased around August 2002. Abdominal CT revealed a recurrent tumor in the RLQ in July 2003, peritoneal dissemination was suspected. In December 2003, we performed a partial resection of the ileum and transverse colon including initial anastomosis. Lung metastases were found by chest CT in right S4, S5, S9 and S3, S8 in February 2004. Because of experience of severe side effect of intravenous chemotherapy, UFT/LV was administered from February 2004. Chest CT revealed the disappearance of tumor in September 2004, and no signs of recurrence were observed for 65 months.

Topics: Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Female; Humans; Leucovorin; Lung Neoplasms; Middle Aged; Neoplasm Staging; Recurrence; Remission Induction; Tegafur; Time Factors; Tomography, X-Ray Computed; Uracil

We report a male patient with double advanced tumors in the jejunum and descending colon and multiple lung tumors. The intestinal cancers were surgically resected. Immunoprofiling of the specimens revealed a rare phenotype: the jejunal cancer was positive for cytokeratin (CK) 7, partially positive for CK20, and Cdx-2-negative, whereas the colon cancer was CK7(+), CK20(-), and Cdx-2(-). Biopsied lung tumor was diagnosed as tubular adenocarcinoma, and CK7(+)/CK20(+)/Cdx-2(-). Together with clinical information, we deduced that the jejunal adenocarcinoma had presumably metastasized to the lung. Moreover, postoperative oxaliplatin, including chemotherapy, significantly reduced the lung metastases, suggesting that this regimen is a promising treatment option for advanced small bowel adenocarcinoma.

Topics: Adenocarcinoma; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Biopsy; CDX2 Transcription Factor; Chemotherapy, Adjuvant; Colectomy; Colonic Neoplasms; Fatal Outcome; Fluorouracil; Homeodomain Proteins; Humans; Immunohistochemistry; Jejunal Neoplasms; Keratin-20; Keratin-7; Leucovorin; Lung Neoplasms; Lymph Node Excision; Male; Middle Aged; Neoplasms, Multiple Primary; Organoplatinum Compounds; Oxaliplatin; Phenotype; Tomography, X-Ray Computed; Treatment Outcome

A 56-year-old man with abnormal chest X-P and stool occult bleeding was admitted. Colonoscopy detected rectal cancer and sigmoid al polyps. The biopsy results suggested that the rectal lesion was well- to moderately-differentiated adenocarcinoma and the sigmoidal polyp contained well -differentiated adenocarcinoma. CT scan revealed multiple lung, liver and lymph node metastasis. We judged the case to be inoperable and decided to start systemic chemotherapy (FOLFOX4). After treatment with chemotherapy, the tumor shrank and metastatic lesions disappeared. Low anterior resection was done, and final pathological examination revealed a complete response of the main tumor by treating with FOLFOX4.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Fluorouracil; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoadjuvant Therapy; Rectal Neoplasms

No standard has been established for salvage therapy in gemcitabine refractory advanced urothelial cancer. We report the complete response to FOLFOX4 therapy of a metastatic urothelial cancer patient, for whom adjuvant gemcitabine plus cisplatin combination chemotherapy had failed. A 54-year-old male patient with urothelial cancer (transitional cell carcinoma) in the right kidney underwent three rounds of adjuvant gemcitabine-cisplatin chemotherapy after extensive radical nephrectomy. However, he had new liver, lung metastases and synchronous two separate primary colon cancer. The lung metastasis lesion was confirmed as a metastatic urothelial cancer via percutaneous transthoracic needle biopsy (PTNB). Liver and lung metastasis lesions disappeared after the 4th cycle of FOLFOX4 chemotherapy. In addition, colon cancer also disappeared after the 8th cycle of FOLFOX4 chemotherapy. The patient was still showing a complete response after 4 months. Clinical trials using the FOLFOX regimen as salvage therapy for gemcitabine-refractory advanced urothelial cancer are warranted.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Transitional Cell; Disease Progression; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Neoplasm Invasiveness; Organoplatinum Compounds; Remission Induction; Treatment Outcome; Urologic Neoplasms; Urothelium

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

A 51-year-old man was referred to our hospital with adenocarcinoma of sigmoid colon with multiple lymph node metastasis. At the time of admission, he had dyspnea, and computed tomography (CT) showed typical signs of lymphangitis carcinomatosa of the lung. Combination of mFOLFOX6 and bevacizumab was started. After start of the therapy, CT revealed an improvement in lymphangitis carcinomatosa. 8 months later, the tumor assessment became progressive disease. FOLFIRI was started as the second-line chemotherapy, but the patient did not respond. Then, dyspnea emerged again, and CT indicated the lymphangitis carcinomatosa had become worse. So as the third-line chemotherapy, combination of irinotecan and cetuximab was started. Dyspnea immediately disappeared, and CT showed an improvement of lymphangitis carcinomatosa. In the previous literature, malignant tumor cases which accompany lymphangitis carcinomatosa might always have a poor course. Our case dramatically responded to the chemotherapy including molecular targeting drug and showed a long survival. So we conclude that aggressive chemotherapy including a molecular targeting drug may be recommended in a case of colorectal cancer which accompanies lymphangitis carcinomatosa of the lung.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Cetuximab; Drug Delivery Systems; Fluorouracil; Humans; Irinotecan; Leucovorin; Lung Neoplasms; Lymphangitis; Male; Middle Aged; Organoplatinum Compounds; Sigmoid Neoplasms

Metastatic urachal cancer is a rare disease and subsequently, does not have a defined systemic treatment. Although urachal cancer is most commonly adenocarcinoma and histologically similar to colon cancer, treatment selection is usually based upon location (the proximity of the urachus to the bladder) with bladder cancer regimens the most commonly prescribed. We report a case of metastatic urachal cancer where the immunohistochemical profile's similarities to colon cancer led to treatment with colon cancer specific chemotherapy. Our case is the first to report urachal cancer treated with and responding to modified FOLFOX6. In the age of targeted therapy, where molecular biology drives treatment selection, our case highlights that in rare tumors, when evidence is often lacking, a common sense approach can often prevail.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cystectomy; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Thyroid Neoplasms; Treatment Outcome; Urachus; Urinary Bladder Neoplasms

The case is a 66-year-old woman. CT showed multiple metastasis of the liver and lung after operation by colectomy for ascending colon carcinoma. A close inspection showed progressive stomach cancer with lymph node metastasis. Metastasis was considered an effect when it was of colon cancer origin, and treatment by mFOLFOX6 was started. In the results, we confirmed contraction of the liver and lung metastasis and contraction of the regional lymph node metastasis of the stomach by CT. The gastric cancer lesion became only a cicatrix with endoscopic examination. For gastric cancer, the availability of mFOLFOX6 was suggested.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Colectomy; Colonic Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Organoplatinum Compounds; Positron-Emission Tomography; Stomach Neoplasms; Tomography, X-Ray Computed

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

We report a rare case of metastatic colorectal cancer who suffered from hyperammonemic encephalopathy induced by 5- FU and was continuously treated with FOLFOX therapy. A 50-year-old man with ileus was diagnosed with ascending colon cancer Stage IV, and a right hemicolectomy was performed. Postoperative chemotherapy with modified FOLFOX6 was performed. Complications of nausea and vomiting were seen on day 2 , with confusion and cognitive disturbances on day 3 . None of the other radiographic examinations provided an explanation for his symptoms. Laboratory examination revealed hyperammonemia, so branched-chain amino acid solutions and high-volume drip infusion were started for its treatment. His symptoms entirely disappeared on day 4. We changed to chemotherapy for FOLFOX4 using branched-chain amino acid solutions and drip infusion. The tumor marker level normalized following two courses, and CT following ten courses showed that the size of the lung metastasis and abdominal lymph node had reduced significantly. The patient is currently receiving FOLFOX4.

Topics: Amino Acids, Branched-Chain; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Combined Modality Therapy; Fluorouracil; Humans; Hyperammonemia; Leucovorin; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Organoplatinum Compounds; Tomography, X-Ray Computed

A 74-year-old man was administered FOLFIRI therapy, followed by modified FOLFOX therapy and FOLFIRI therapy due to ascending colon carcinoma with multiple lung metastases. After 19 months, the tumor marker became normal, and CT and PET-CT revealed the multiple lung metastases had disappeared. He was operated due to stenosis of the ascending colon carcinoma, and is now being treated with chemotherapy due to liver metastasis. There has been no regrowth of lung metastases for 21 months since the disappearance of multiple lung metastases.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Organoplatinum Compounds; Positron-Emission Tomography; Tomography, X-Ray Computed

Hypersensitivity reaction (HSR) and sensory neuropathy are major complications of oxaliplatin-based chemotherapy. Preplanned withdrawal of oxaliplatin after the first six cycles and reintroduction at the time of disease progression (stop-and-go strategy) may reduce neurotoxicity. However, the effect of an oxaliplatin-free interval on HSR occurrence remains poorly understood.. Data on patients with colorectal cancer who received FOLFOX (5-fluorouracil, leucovorin and oxaliplatin) treatment between June 2005 and June 2009 were retrieved from the prospective cohort database of the Outpatient Oncology Unit of the Kyoto University Hospital. Factor analysis was performed.. Among patients who received six or fewer cycles of FOLFOX, the incidence of HSR was low (7/99, 7.1%). For patients who received more than six cycles, the incidence of HSR was higher among patients treated with stop-and-go FOLFOX than among patients treated with continuous FOLFOX (25/61, 41.0% vs. 13/63, 20.6%; p = 0.019). Interestingly, most cases of HSR during stop-and-go FOLFOX occurred during the second or third cycle of the reintroduction phase (21/25, 84%). Multivariate analysis identified undergoing an oxaliplatin-free interval as an independent risk factor (p = 0.016).. An oxaliplatin-free interval may increase the risk of HSR. Special vigilance is needed during the second and third cycles after reintroduction of oxaliplatin.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Drug Administration Schedule; Drug Hypersensitivity; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Logistic Models; Lung Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Risk Factors; Time Factors

A-75 year-old man, diagnosed as ascending colon cancer with large bowel obstruction, multiple hepatic, lunge metastases and peritoneal dissemination, was treated with neoadjuvant chemotherapy (FOLFOX4: 2 courses) and subsequent ileocecal resection. Postoperative systemic chemotherapy with hepatic arterial infusion (HAI) of 5-FU was performed in the following fashion: FOLFOX4, FOLFIRI with or without bevacizumab or cetuximab was administered every 4 weeks and a weekly HAI twice every 4 weeks. By those treatments, the patient could maintain a 30-month long NC effect and a good performance status.

Topics: Aged; Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Cetuximab; Colonic Neoplasms; Fluorouracil; Hepatic Artery; Humans; Infusions, Intra-Arterial; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Neoadjuvant Therapy; Organoplatinum Compounds

We report a case of multiple lung and liver metastases from colon cancer treated with clinical benefit by hepatic arterial infusion chemotherapy plus cetuximab mono-therapy after a standard chemotherapy was failed. A 61-year-old female who had sigmoid colon cancer with unresectable multiple lung and liver metastases underwent sigmoidectomy. Bevacizumab plus mFOLFOX6 was performed as first-line therapy. Partial response was obtained temporarily. After the first-line therapy failed, bevacizumab plus FOLFIRI as second-line, and cetuximab plus CPT-11 as third-line therapy were performed. Since these regimens did not work, her performance status got worse by cholangitis due to progressive liver metastases and anemia. Hepatic arterial infusion chemotherapy for liver metastases and cetuximab for lung metastases as fourth therapy were chosen because we thought her liver metastases should be critical for the maintenance of her QOL and diagnosis. After that, serum CEA was reduced from 14,715 to 6,940 ng/mL during the 3 month period. And her performance status got better as cholongitis and anemia were improved. Additionally, lung metastases were controlled by cetuximab.

Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Carcinoembryonic Antigen; Cetuximab; Female; Fluorouracil; Hepatic Artery; Humans; Infusions, Intra-Arterial; Irinotecan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Middle Aged; Organoplatinum Compounds; Sigmoid Neoplasms

A 60-year-old male underwent sigmoidectomy for sigmoid colon cancer with synchronous multiple liver and lung metastases. Six weeks after the sigmoidectomy, mFOLFOX6 + bevacizumab (Bmab) was initiated. After 7 courses, lung tumors were almost disappeared and liver tumors shrunken up to 69% in size, and metastasectomy of liver tumors was performed with R0 resection. Pathological examination disclosed that tumor response to chemotherapy was Grade 2. mFOLFOX6 + Bmab, FOLFIRI + Bmab, and cetuximab were administered after liver surgery before the patient died 25 months after the sigmoidectomy. Combination therapy of metastasectomy and intensive chemotherapy might benefit to prolong survival of the patient.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Cetuximab; Colectomy; Colon, Sigmoid; Fluorouracil; Hepatectomy; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Sigmoid Neoplasms

A 73-year-old man underwent a sigmoid colon resection and an insertion of a hepatic arterial infusion catheter for multiple liver metastases from sigmoid colon cancer. After the hepatectomy, the patient was detected a lung metastasis and was scheduled to undergo mFOLFOX6 chemotherapy. The tumor lesion was reduced once in size, but it has grown again after the chemotherapy. So, we underwent a stereotactic radiotherapy (60 Gy/10 Fr). The tumor lesion became a scar and the patient was doing well without any recurrence at 21 months after undergoing stereotactic radiotherapy. Lung resection has a better result than other treatments for a lung metastasis caused from colon cancer, but there are some cases with no indication of the operation due to a complication. Stereotactic radiotherapy can be an effective treatment for lung metastasis from colon cancer with no indication of the operation.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Organoplatinum Compounds; Radiosurgery; Sigmoid Neoplasms

Uterine bleeding frequently complicates gestational trophoblastic disease, particularly after uterine evacuation. Hysterectomy and other procedures used to control this bleeding incur significant risk and can limit fertility.. We present a case of massive hemorrhage complicating uterine curettage performed for metastatic gestational trophoblastic disease. The patient's bleeding was controlled successfully by intrauterine tamponade performed using a balloon catheter. After catheter removal, she achieved complete disease remission.. Intrauterine balloon catheterization appears to be a promising alternative to control uterine hemorrhage and preserve fertility for young women undergoing treatment for gestational trophoblastic disease. Its use may help avoid invasive interventions, such as hysterectomy and embolization, currently used to control hemorrhage after uterine evacuation.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Balloon Occlusion; Catheterization; Dactinomycin; Dilatation and Curettage; Etoposide; Female; Gestational Trophoblastic Disease; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Pregnancy; Uterine Hemorrhage

The GONO-FOLFOXIRI regimen improved the rate of R0 secondary resection of metastases in initially unresectable metastatic colorectal cancer. The objective of this study was to evaluate the long-term outcome of resected patients and the impact of FOLFOXIRI on perioperative morbidities, mortality, and chemotherapy induced hepatotoxicity.. Overall, 196 patients with initially unresectable metastatic colorectal cancer were treated with FOLFOXIRI in 2 phase II and 1 phase III trial. This regimen was associated with an elevated response rate (70.4%) and 37 patients (19%) could undergo a secondary R0 surgery on metastases. This study was registered with the Australian New Zealand Clinical Trials Registry Database at http://www.anzctr.org.au/Statistics.aspx and has ID number ACTRN12608000615381.. Main characteristics of the 37 radically resected patients were: median age 64 years (45-73), Eastern Cooperative Oncology Group Performance Status (ECOG) PS > or = 1 in 30%, synchronous metastases in 65%, multiple sites of disease in 22%, and metastases confined to the liver in 68%. Preoperative FOLFOXIRI was administered for a median of 5.5 months. There was no perioperative mortality and all morbidities (27% of patients) resolved without sequelae. After a median follow up of 67 months, 5-year and 8-year survival are 42% and 33% respectively. At 5 years, 29% of patients are free of disease. The analysis of treatment-induced liver injury showed neither G3 vascular toxicity nor G4 steatosis, and steato-hepatitis in only 5% of patients.. The GONO-FOLFOXIRI regimen allow an R0 surgery in approximately 1 out of 5 unselected patients with initially unresectable metastatic colorectal cancer, and the long-term survival of resected patients is considerable. Neoadjuvant FOLFOXIRI for 3-6 months is safe and not associated with severe liver injury.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Female; Fluorouracil; Hepatectomy; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Pneumonectomy; Treatment Outcome

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Capecitabine; Chemotherapy, Adjuvant; Colectomy; Colorectal Neoplasms; Deoxycytidine; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Oxaloacetates; Research Design; Retrospective Studies; SEER Program; Unnecessary Procedures

A postoperative rectum cancer patient with lung metastasis undergoing hemodialysis was treated with mFOLFOX6 therapy. The primary dose of oxaliplatin (L-OHP) ranged from 60 mg/m(2) to 85 mg/m(2), and adverse reactions and serum platinum concentration were monitored. The free platinum concentration (f-Pt), was eliminated efficiently using dialysis. The patient was tolerant of L-OHP doses of 60 mg/m(2) and 70 mg/m(2), but grade 2 neutropenia and grade 3 hemoglobin decrease developed with an L-OHP dose of 85 mg/m(2). The f-Pt after hemodialysis was higher than that before hemodialysis with a dose of 85 mg/m(2). But even with an 85 mg/m(2) dose, mFOLFOX6 therapy could be continued by extending the dosing interval. The monitoring of serum platinum concentrations, as well as therapeutic monitoring based on pharmacokinetics, contributes to safety management of cancer chemotherapy.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms; Renal Dialysis

An increase in carcinoembryonic antigen (CEA) and/or carbohydrate antigen 19-9 (CA19-9) levels is generally considered as tumor progression in patients with metastatic colorectal cancer (MCRC). However, a transient CEA surge has been observed in patients with MCRC responding to chemotherapy. This study was to investigate the clinical significance of transient CEA/CA19-9 surges in Chinese MCRC patients.. One hundred and twenty-one MCRC patients with histologically proven adenocarcinoma and baseline ECOG performance status of < or =2 were treated with oxaplatin and (or) irinotecan-based chemotherapy regimens. Serum CEA and CA 19-9 levels were measured before and after chemotherapy.. Of the 121 patients, 14 (11.6%) had transient CEA surges with median baseline CEA level of 45 microg/L (9.67-2208 microg/L) and median surge peak level of 80.1 microg/L (13.38-4044 microg/L). The transient CEA surge occurred at a median of 4 weeks (2-6 weeks), and lasted for a medium of 6.5 weeks (4-14 weeks). Of the 14 patients, 11 received oxaplatin-based chemotherapy; three received irinotecan-based chemotherapy. All the 14 patients showed clinical benefit from chemotherapy, among which seven achieved partial response and seven had stable disease. In the meantime, five patients (3.8%) had transient CA19-9 surges. However, no significant correlation was found between an increase in the CA19-9 level and clinical benefits.. Transient CEA surges can be observed in Chinese MCRC patients receiving oxaplatin or irinotecan-based chemotherapy, which does not indicate tumor progression, but good therapeutic efficacy. A transient elevation of CA19-9 is not correlated to short-term clinical benefits.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; CA-19-9 Antigen; Camptothecin; Capecitabine; Carcinoembryonic Antigen; Child; Colonic Neoplasms; Deoxycytidine; Disease Progression; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Oxaloacetates; Rectal Neoplasms; Remission Induction; Young Adult

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Clinical Trials, Phase III as Topic; Colorectal Neoplasms; Fluorouracil; Hepatectomy; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymph Node Excision; Lymphatic Metastasis; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Organoplatinum Compounds; Oxaliplatin; Pneumonectomy; Survival Rate; Treatment Outcome

Rectovaginal fistula in long-standing Crohn's disease is possibly associated with malignant transformation to mucinous adenocarcinoma of the vagina. However, there have been no previously reported cases documenting vulvar cancer in association with rectovaginal fistula in Crohn's disease. We report 2 cases of vulvar mucinous adenocarcinoma associated with Crohn's disease. Both showed vulvar symptoms after the development of rectovaginal fistula. CASE 1: A 48-year-old woman, with a 30-year history of Crohn's disease including a rectovaginal fistula, developed persistent pyoderma gangrenosum. Further workup revealed metastatic vulvar mucinous adenocarcinoma. CASE 2: A 37-year-old woman with long-standing Crohn's disease including numerous episodes of perianal or rectovaginal fistulas complained of a vulvar mass suspicious for an abscess. Biopsy showed mucinous adenocarcinoma.. Vulvar lesions or symptoms in the setting of rectovaginal fistula in Crohn's disease are an important clinical feature and the possible development of vulvar cancer should be considered.

Topics: Adenocarcinoma, Mucinous; Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Biopsy, Fine-Needle; Crohn Disease; Diagnosis, Differential; Female; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Positron-Emission Tomography; Rectovaginal Fistula; Vulvar Neoplasms

A 64 -year-old female received oral S-1 chemotherapy followed by mFOLFOX6 chemotherapy for postoperative liver and lung metastasis of sigmoid colon cancer. The tumor progression was observed after twelve courses of mFOLFOX6 chemotherapy, and then FOLFIRI+bevacizumab chemotherapy was performed. After two courses of FOLFIRI+bevacizumab chemotherapy, leucopenia was observed. The chemotherapy was then discontinued and G-CSF was administered. Two days later she complained of high fever and dry cough, and was admitted to the hospital. A diffuse ground-glass appearance of bilateral lung was observed on chest X-ray and CT. Drug-induced interstitial pneumonitis was suspected, and Pneumocystis carini pneumonia was considered in the differential diagnosis. Oral administration of prednisolone and sulfamethoxazole/trimethoprim did not improve the symptoms, so steroid pulse therapy was performed. Steroid pulse therapy improved respiratory symptoms, but CT findings did not change remarkably. After nine weeks in the hospital, she was discharged with home oxygen therapy. Interstitial pneumonitis induced by FOLFIRI+bevacizumab chemotherapy is rare, but the number of cases may increase with increased use of this regimen. The possibility of interstitial pneumonitis should always be considered when the patient presents with a respiratory disorder while receiving systemic chemotherapy.

Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Lung Diseases, Interstitial; Lung Neoplasms; Middle Aged; Sigmoid Neoplasms

We described two resected cases of pulmonary metastasis from postoperative colorectal cancer after preoperative FOLFOX chemotherapy. Pathologic histology inspection of the tumor was judged to be effective prior to resection. The first case is a 68-year-old male who underwent a sigmoidectomy as a stage III A sigmoid colon cancer in March 2003. Afterwards, distant metastases had occurred to the liver, the left lung and neck lymph nodes from 2003 to 2006. Three operations and systemic chemotherapy were performed. A new metastasis of the right lung occurred in November 2006. The FOLFOX chemotherapy was performed 7 times, the tumor was not changed in the image, and the effect judgment was SD. After the chemotherapy, a partial resection of the right lung was performed in November 2007. Half of the tumor resulted in necrosis on the specimen (Grade 1b). The second case is a 63-year-old female who underwent an anterior resection of the rectum as a stage II rectal cancer in January 2000, a partial resection of the right lung as a metachronous right pulmonary metastasis in March 2003, and post operative chemotherapy (IFL) were performed. A new metastasis of the right lung occurred in September 2005. The FOLFOX chemotherapy was performed 4 times, the tumor was not changed in the image, and the effect judgment was SD. After the chemotherapy, a partial resection of the right lung was performed in April 2006. One third of the tumor resulted in necrosis on the specimen (Grade 1a).. It was thought that FOLFOX chemotherapy can be a promising candidate for neoadjuvant treatment of pulmonary metastasis from postoperative colorectal cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Pneumonectomy

Nasopharyngeal carcinoma (NPC) is a disease that is highly responsive to various chemotherapeutic agents. In the metastatic setting, 2-drug combination chemotherapy generally provides a response rate of 55% to 75%, and median survival of 10 to 12 months. The objective of the current study was to assess the efficacy of a 3-drug combination followed by maintenance treatment in patients with metastatic NPC.. Patients with metastatic NPC were treated with a combination of gemcitabine at a dose of 1,000 mg/m(2), paclitaxel at a dose of 70 mg/m(2), and carboplatin at an area under the concentration-time-curve (AUC) of 2.5 on Days 1 and 8 every 21 days. Patients who achieved partial or complete response continued to receive weekly 5-fluorouracil at a dose of 450 mg/m(2) and leucovorin at a dose of 30 mg/m(2) for 48 weeks.. Twenty-eight patients were recruited. Twenty-two (79%) patients had >or=2 sites of disease. Toxicities were mainly from bone marrow suppression, with 79% grade 3/4 neutropenia, 32% grade 3/4 anemia, and 29% grade 3/4 thrombocytopenia (according to the National Cancer Institute Common Toxicity Criteria). The overall response rate to the 3-drug regimen was 86%, with a complete response rate of 11%. The median duration of response was 8 months and the median overall survival was 22 months.. This regimen of a 3-drug combination followed by maintenance is feasible and has demonstrated an encouraging response rate and overall survival.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Carboplatin; Deoxycytidine; Feasibility Studies; Female; Fluorouracil; Follow-Up Studies; Gemcitabine; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Maximum Tolerated Dose; Middle Aged; Nasopharyngeal Neoplasms; Paclitaxel; Prognosis; Quality of Life; Survival Rate

A 78-year-old male with sigmoid colon cancer underwent sigmoidectomy. The lesion was se, p1(+), n1, and Stage IV. Oral UFT therapy was performed, but was replaced with oral S-1 therapy 1 year and 6 months after surgery. Three months later, lung metastases 2.0 x 1.5 cm and 0.6 x 0.6 cm were found by chest CT in right S10a and S5b, respectively. Since the patient did not wish surgery, the treatment was changed to oral UFT/Leucovorin(LV)therapy(UFT 300 mg/ LV 75 mg, 4-week administration and 1-week no-administration periods). After 2 courses, chest CT showed disappearance of both lung metastases, indicating complete remission. Oral UFT/LV therapy is convenient because of the oral route. Adverse reactions are few, and the therapeutic effect has been reported to be comparable to that of intravenous 5-FU/LV therapy. Also, in this patient, no adverse reaction was noted, and complete remission was maintained until the patient died of another disease 31 months after the beginning of oral UFT/LV therapy.

Topics: Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Humans; Leucovorin; Lung Neoplasms; Male; Radiography; Tegafur; Uracil

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

The patient was a 62-year-old male who underwent a high anterior resection for rectal cancer with multiple liver metastases in June 2004. After the operation, 66 courses of weekly hepatic arterial infusion(HAI)therapy of 5-FU/Leucovorin( LV)were performed. Thereafter 14 courses of FOLFOX 4, 5 courses of FOLFIRI and 5 courses of FOLFOX 4 therapy were also sequentially performed. As a result of the CT examination, which revealed a new metastatic lesion in the liver and lung metastases, combination chemotherapy consisting of UFT and HAI of low-dose CPT-11 was administered in July 2007. After 1 cycle of this therapy, metastatic liver and lung tumors showed a reduction rate of 8.5% and 27.0%, respectively, without any adverse events. The elevated serum CEA (2,055 ng/mL)and CA19-9 (924 U/mL) levels decreased to 623 ng/mL and 332U /mL, respectively, after 1 cycle of the treatment. The combination of oral UFT and HAI of CPT-11 may therefore be a useful treatment for patients after FOLFOX and FOLFIRI therapy.

Topics: Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Camptothecin; Fluorouracil; Humans; Infusions, Intra-Arterial; Irinotecan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Rectal Neoplasms; Tegafur; Tomography, X-Ray Computed; Uracil

Oxaliplatin has been approved for adjuvant treatment of colorectal cancer. Toxicity induced by oxaliplatin is moderate and manageable, but some isolated cases of severe pulmonary toxicity associated to oxaliplatin have been reported. Two fatal cases of interstitial pneumonitis rapidly evolving to pulmonary fibrosis are reported here.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Fatal Outcome; Female; Fluorouracil; Granulomatosis with Polyangiitis; Humans; Leucovorin; Lung Diseases, Interstitial; Lung Neoplasms; Male; Organoplatinum Compounds; Oxaliplatin; Pneumonectomy; Postoperative Complications; Pulmonary Alveoli; Pulmonary Fibrosis; Respiratory Distress Syndrome; Sigmoid Neoplasms; Tomography, X-Ray Computed

Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Brain Neoplasms; Breast Neoplasms; Camptothecin; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Chemotherapy, Adjuvant; Colorectal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Mass Screening; Medical Oncology; Neoplasms; Organoplatinum Compounds; Societies, Medical

There are different types of skin changes associated with internal malignancy. One type is the skin involvement as a result of cutaneous metastasis from an internal tumor. The skin is an uncommon site for distant metastasis; when it is present the most common sources are breast, lung, and colon. Metastasis generally occurs after an internal malignancy had been discovered and signifies disseminated disease with a poor prognosis. We report an exuberant and rare case of cutaneous metastasis from gastric adenocarcinoma as the first sign of this serious visceral cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cachexia; Carcinoma, Signet Ring Cell; Etoposide; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Skin Neoplasms; Spinal Neoplasms; Stomach Neoplasms; Treatment Failure

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colorectal Neoplasms; Fatal Outcome; Fluorouracil; Humans; Irinotecan; Leucovorin; Lung Neoplasms; Male; Middle Aged; Tumor Lysis Syndrome

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Choriocarcinoma; Dactinomycin; Doxorubicin; Endometrium; Etoposide; Female; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Pregnancy; Uterine Neoplasms; Vincristine

Oxaliplatin is a third generation platinum compound used in patients with advanced colorectal carcinoma. Recently, the mechanism of a rare drug-induced immune thrombocytopenia in patients receiving oxaliplatin has been described. This complication is caused by oxaliplatin-dependent antibodies directed against platelet surface glycoproteins, and is unrelated to myelosuppression. In this report, we describe two patients who developed thrombocytopenia immediately soon after receiving oxaliplatin. Sensitization presumably had occurred after receiving oxaliplatin during preceding courses of multiagent chemotherapy that included oxaliplatin.

Topics: Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Blood Platelets; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Membrane Glycoproteins; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms; Thrombocytopenia

The chemotherapy regimen suitable for advanced colorectal cancer patients previously treated with 5 fluorouracil (5FU); oxaliplatin and irinotecan remains an unresolved issue. The poor response rates and progression-free survival achieved with FOLFIRI in the second-line of therapy and the schedule-dependent activity of irinotecan, prompted us to assess the efficacy and tolerability of FOLFIRI3 regimen in patients with metastatic colorectal cancer (CRC) previously exposed to irinotecan and oxaliplatin.. Twenty-seven metastatic CRC patients previously exposed to irinotecan and/or oxaliplatin were treated with the FOLFIRI3 regimen. They received an irinotecan injection at 100 mg/m(2) before and at the end of a 2400 mg/m(2) 5FU continuous infusion. Two hundred and six cycles of chemotherapy were delivered in an outpatient basis.. FOLFIRI3 regimen was well tolerated. Grade 3 of 4 adverse events included nausea and vomiting (18%), diarrhea (11%), anemia (7%), and neutropenia (7%). Partial responses were observed in 2 patients and 10 patients achieved stable diseases. From the start of FOLFIRI3, time to progression was 4.47 months (0-11 months) and median overall survival was 8.9 months (0.72-21.4 months). Interestingly, FOLFIRI3 treatment was associated to a clinical benefit in 7 out of 17 patients who previously progressed "on-therapy" or less than 3 months after the completion of a previous FOLFIRI chemotherapy.. These results suggest that fractionated irinotecan administration might restore the clinical benefit of this molecule in patients resistant to FOLFIRI.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Colorectal Neoplasms; Disease Progression; Drug Resistance, Neoplasm; Female; Fluorouracil; Humans; Infusions, Intra-Arterial; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Retrospective Studies; Survival Rate

We report two cases of recurrent colorectal cancer in two patients who were treated successfully with a combined oral chemotherapeutic agent folinate/tegafur/uracil (UFT/LV) dosage. The first case was a 74-year-old woman who underwent Hartmann operation for colon cancer perforation. One year and 7 months after surgery, a local recurrence was found on the CT scan and endoscopy. It ended in exploratory laparotomy though we were operated on. Chemotherapy using 5-fluorouracil/Leucovorin (5-FU/LV) was performed six times. Sequentially, UFT/LV internal use was managed at our outpatient clinic. This patient has been living without side effects in the first three postoperative years, and without increase in tumors. The second case was a 65-year-old woman who underwent abdominoperineal resection of the rectum for rectal cancer. The histologic stage of disease aggravation of the patient was stageI. Post operatively, 2 years and 6 months later, we recognized a metastasis node on the lung upper right lobe of the patient and her CA19-9 value climbed dramatically. The patient took UFT/LV during outpatient visits to the hospital, the lung node shadow disappeared two months later, and CA19-9 decreased, too. The patient is living without a cancer recurrence now. UFT/LV treatment is one of the effective modalities against recurrence of colorectal cancer from outpatient treatment while maintaining QOL.

Topics: Aged; Ambulatory Care; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Colorectal Neoplasms; Female; Humans; Leucovorin; Lung Neoplasms; Recurrence; Tegafur; Tomography, X-Ray Computed; Treatment Failure; Uracil

A 56-year-old woman with multiple lung metastases and lymphangiosis carcinomatosa due to recurrent rectal cancer was treated with chemotherapy of modified FOLFOX6 (mFOLFOX6) regimen: l-leucovorin (l-LV 200 mg/m(2)) and oxaliplatin (L-OHP 85 mg/m(2)) were given as a 2-hour infusion followed by bolus injection of 5-FU 400 mg/m(2) and a 46- hour infusion 5-FU 2,400 mg/m(2) every two weeks. Since partial response was achieved and dyspnea was remarkably improved, she was discharged without oxygen therapy after 5 courses.

Topics: Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Lymphatic Metastasis; Middle Aged; Neoplasm Recurrence, Local; Organoplatinum Compounds; Rectal Neoplasms

We have treated 14 advanced and metastatic colorectal cancers with irinotecan (CPT-11) plus fluorouracil (5-FU) and l-leucovorin (l-LV) combination chemotherapy. The 14 patients consisted of 8 males and 6 females with a mean age of 65 years. We diagnosed adenocarcinoma of the colon in 10 patients and of the rectum in 4 patients. Four patients had liver metastases, five had lung metastases, and one had both, while one had lung and lymph node metastases, two had lymph node metastases and one had a local recurrence. The chemotherapy consisted of CPT-11 100 mg/m(2) div, as a 150-minute infusion, simultaneously l-LV 10 mg/m(2) div, as a 30-minute infusion, followed by 5-FU 500 mg/m(2) iv, as a bolus injection. This treatment was administered weekly for 2 weeks followed by a 2-week rest period and repeated every 4 weeks. All patients received this regimen as first-line chemotherapy. All patients were evaluated for efficacy 1 CR, 2 PR, 9 SD, and 2 PD. The overall response rate was 21.4% with a median time to progression of 8.1 months and a median survival time of 18.6 months. Grade 3 nausea, diarrhea and the suppression of white blood cells were seen in 3 patients, respectively. All other adverse reactions were mild (grade 1 or 2). Except for one patient,residual patients were able to receive the systemic chemotherapy on schedule. CPT-11/5-FU/l-LV combination chemotherapy appears to be effective first-line chemotherapy for advanced and metastatic colorectal cancer.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Rectal Neoplasms; Retrospective Studies

FOLFOX regimens were administered to 14 patients with unresectable advanced or recurrent colorectal cancer from 1 to 9 cycles (median 5 cycles). In our patient characteristics, 10 patients had previous chemotherapies, 3 patients showed performance status 3. The response rate was 21%, and median time to progression was 5.0 months. Frequency of grade 3/4 adverse effect was 57% in neutropenia, 36% in leucopenia, 36% in thrombocytopenia, and 7% in allergic reaction. Only 64% patients could complete the treatment, for these adverse events brought treatment failure at 3-6 cycles. Median relative dose-intensity was 80-90% during 1-4 cycles, but about 50% after 5 cycles for these adverse events. No patient had grade 3 neurologic toxicity,because no one was administered over 10 cycles. FOLFOX regimens showed good anti-tumor effects but poor tolerability after 5-6 cycles in our patients.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Liver Neoplasms; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neutropenia; Organoplatinum Compounds

Topics: Adenocarcinoma; Aged; Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Cetuximab; Colonic Neoplasms; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Receptors, Cell Surface; Treatment Outcome

In order to distinguish the differences in standard treatment for colorectal cancer between Japan and Western countries, we compared several issues in clinical practice guidelines (guidance) of Japan, the United States and the United Kingdom. Endoscopic resection is not common in Western countries, so its feasibility and efficacy should be determined in Japan. Laparoscopic resection, however, is applied to more advanced diseases. Expansion of the indication is now also under consideration in Japan a waiting the results from clinical trials. Although with chmeotherapy for advanced or metastatic diseases, the use of molecular targeting agents is recommended in the United States, it is not in the United Kingdom mainly because it is not cost-effective. The indication of adjuvant chemotherapy is similar in Japan and Western countries. Patients with Stage III disease and high-risk Stage II are good candidates for adjuvant chemotherapy. Enrollment in clinical trial should be considered for remaining Stage II patients. Surgery is considered to be the major treatment modality in Japan for the treatment of liver and lung metastases and advanced rectal cancer. However, neo-adjuvant chemo (-radio) therapy is considered to be the standard treatment in Western countries. Development of a new treatment modality for colorectal cancer has progressed very rapidly, and the standard treatment has changed dramatically. While guidelines should be revised frequently according to new evidence, the standard treatment must be cautiously determined based on cost-effectiveness.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Colorectal Neoplasms; Combined Modality Therapy; Fluorouracil; Gastrectomy; Humans; Japan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Organoplatinum Compounds; Practice Guidelines as Topic; Radiotherapy, Adjuvant; United Kingdom; United States

A case of colorectal cancer in a 60-year-old man became resectable after downstaging was achieved with mFOLFOX 6 for multiple liver metastases from colorectal cancer. The patient received 8 cycles of mFOLFOX 6 on the basis of a diagnosis of multiple liver metastases in the right and left lobes and a single metastasis in the right lung. After chemotherapy, the liver metastases showed partial response, and the lung metastasis stable disease. Because the lung metastasis was controlled and radical cure of the liver metastases was thought possible by resection, we performed right lobectomy of the liver. Postoperative progress was good, and we then planned a staged partial resection of the lung. However,on postoperative day 28, the patient was hospitalized again with liver dysfunction, which evolved into liver failure, in spite of conservative treatment. The patient died on postoperative day 95. The needle biopsy specimens of the liver taken on readmission showed bile duct occlusion, portal hypertension, and perisinusoidal fibrosis, and histopathology of the surgical non-tumoral liver specimen showed the same findings. We think that liver failure was triggered by resection of the liver which had been damaged by mFOLFOX 6. Recently, liver damage due to oxaliplatin was reported, and evaluation of liver injury is considered important before liver resection for colorectal liver metastases with neoadjuvant FOLFOX.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colorectal Neoplasms; Combined Modality Therapy; Fluorouracil; Hepatectomy; Humans; Leucovorin; Liver Failure; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Organoplatinum Compounds

There are a few clinical trials of combination chemotherapy of oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX-4) in Japan, and its efficacy and safety have not been confirmed yet, especially clinical experience in patients with prior chemotherapy.. To analyze the efficacy and safety of FOLFOX-4 in patients with colorectal cancer who received prior chemotherapy.. Twenty patients were treated with FOLFOX-4 beginning in April 2005. Three patients were entered into the safety study, and seventeen patients were treated on a reduced dose, because they had already received heavy doses of prior chemotherapy.. Number of prior chemotherapy was 1 regimen in 7 patients, more than two regimens in 13 patients. The median course of FOLFOX-4 was 10 (4-12), which gave an overall response rate of 20.0% and a median time to progression of 5.0 months. The median survival time was 15.6 months from initiation of the FOLFOX-4, and 28.5 months from the first-line treatment. Grade 3/4 neutropenia was seen in 12 patients (60%), and neuropathy was observed in 11 patients (55%). No response was seen in irinotecan based regimens after FOLFOX-4.. FOLFOX-4 in patients with pretreated colorectal cancer was effective, and contributed to prolonged life with the TTP of 5 months. However, hematological toxicity was high despite the reduced dose. Further extension of prolonged life is anticipated by administering incorporating molecular targeting agents.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Drug Administration Schedule; Fatigue; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Liver Neoplasms; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neutropenia; Organoplatinum Compounds; Rectal Neoplasms; Salvage Therapy; Survival Rate

The patient was a 63-year-old man,who first visited our hospital with the chief complaints of left lower quadrant pain and abdominal distension that had developed around November 13, 2004. On close examination, he was diagnosed with sigmoid colon cancer, multiple liver metastasis, and subileus due to a lung metastasis. His operation took place on December 12 of the same year. Intraoperatively, the sigmoid colon was firmly fixed to the retroperitonium, there was a hard node in the pouch of Douglas, and that part of the jejunum was involved. The lesion was judged to be unresectable,and thus loop colostomy, partial jejunectomy and gastrojejunostomy were performed. After the surgery,the patient was treated with 4 courses of therapy with oral Leucovorin (LV, 75 mg) +oral tegafur/uracil (UFT, 400 mg). As a result, the tumor marker levels decreased markedly, the lung metastasis was no longer observed and the liver metastases became smaller. Therefore, a second-look operation was performed on May 30, 2005. This time it was relatively easy to free the sigmoid colon. The node in the pouch of Douglas was no longer observed, and there were only 2 metastatic lesions in the liver (1 each in S 2 and S 6). Sigmoidectomy and partial hepatectomy were performed, and the stoma was closed. The patient made good progress after the operation and was discharged on the 11 th POD. At present he is receiving chemotherapy with UFT+oral LV as an outpatient. As this therapy is relatively easy to perform and imposes only a small burden on patients,we think that it may be effective not only as adjuvant chemotherapy but also as neoadjuvant chemotherapy in some patients.

Topics: Adenocarcinoma; Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Colon, Sigmoid; Combined Modality Therapy; Drug Administration Routes; Drug Combinations; Gastric Bypass; Hepatectomy; Humans; Jejunum; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoadjuvant Therapy; Palliative Care; Second-Look Surgery; Sigmoid Neoplasms; Tegafur; Uracil

Amyotrophic lateral sclerosis (ALS) is a degenerative disease involving both upper and lower motor neurons and the pathogenesis of this disorder is still unknown. To date, few reports have suggested that motor neuron diseases may have a paraneoplastic origin. However, it is still under discussion whether ALS occurring in cancer patients is paraneoplastic. A 60-year-old man with rectal cancer (Stage IV) having multiple lung, liver and para-aortic lymph node metastases underwent anterior resection of the rectum as palliative surgery. He was referred to our hospital for adjuvant chemotherapy. Lung and lymph node metastases decreased after 2 courses of chemotherapy using CPT-11 and 5-FU/LV but liver metastases were enlarged, following up increase in CEA. Thereafter, he suffered from muscle weakness in hands, arms, and legs and results of neurophysiologic studies were compatible with primary lateral sclerosis (ALS). For second line chemotherapy, he was treated with low-dose CDDP/5-FU over 6 courses. As a result, the size the of metastatic lesions markedly reduced and CEA was decreased to the normal level. Although significant tumor reduction was observed, his neurological symptoms rapidly progressed. He died of aspiration pneumonia 8 months after onset of the disease. Autopsy revealed that his neuropathological findings were compatible with ALS, and it was thought to be the primary cause of death in the because of absence of cancer progression. In this case the neurological syndrome was not affected by cancer therapy. Thus our case does not support the hypothesis that ALS in associated with cancer and the relationship between both disorders remains uncertain.

Topics: Adenocarcinoma; Amyotrophic Lateral Sclerosis; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Colonic Neoplasms; Drug Administration Schedule; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged

We performed FOLFOX 4 therapy in a patient with lung metastasis (a 62-year-old woman) after surgery for rectal cancer and observed both normalization of tumor markers and disappearance of the metastasis. Low anterior resection was performed for progressive rectal cancer, and treatment with UFT and folinate was started one month after surgery. However, tumor markers increased after 2 months of treatment and CT scans showed metastases to both lungs. FOLFOX 4 therapy was started, and tumor markers became normal after four courses, while the lung metastases disappeared after 10 courses. The dosage of FOLFOX 4 was reduced after three courses due to neutropenia and diarrhea. This treatment appeared to be effective for the inhibition of lung metastasis associated with colorectal cancer.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Combined Modality Therapy; Drug Administration Schedule; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Lung Neoplasms; Middle Aged; Organoplatinum Compounds; Rectal Neoplasms

Oxaliplatin (L-OHP) was administered to 10 patients previously treated for refractory advanced or recurrent colorectal cancer. The number of times each had received previous chemotherapy treatment ranged from 1 to 5 (median 3) for durations of 2.5 to 52.8 (median 11.7) months. At the time, L-OHP was not yet approved for sale in Japan, and could only be imported from overseas for personal use. As this made it very expensive,we used a low L-OHP dose of 100 mg/body. Combinations with 5-FU were administered differently from previous regimens; these included chronotherapy, weekly high-dose, FOLFOX 4, and FOLFOX 6. L-OHP was administered from 1 to 14 times (median 4.5), and the response to treatment was PR in 2 patients and NC in 5. The response rate was 22.2%. Although in NC there was a tendency toward tumor reduction in 2 of the 5 patients, the treatment had to be suspended because of their financial situations. Overall survival from commencement of the first treatment was 3.1 to 58.7 months (median 17.6+) and after starting L-OHP was 0.6 to 17.2 months (median 6.4+). Adverse events included bone marrow suppression in three patients, 3 cases of leukocytopenia (grade 3 in two patients and grade 4 in one), grade 4 thrombocytopenia in one patient,grade 3 sensory disturbance in one patient,and grade 3 anorexia in two patients. All reactions were able to be controlled except for one patient with Grade 4 thrombocytopenia. In summary,treatment with L-OHP as salvage chemotherapy can possibly contribute to prolongation of survival time in cases of refractory advanced colorectal cancer. It is useful to combine L-OHP with high-dose continuous administration of 5-FU,namely FOLFOX regimens.FOLFOX 6 is the most useful of the FOLFOX regimens because it is simple and can be administered on an outpatient basis.

Topics: Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Liver Neoplasms; Lung Neoplasms; Male; Maximum Tolerated Dose; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Salvage Therapy; Thrombocytopenia

We have experienced 56 cases of advanced and recurrent colorectal carcinoma treated with 5-Fluorouracil (5-FU)/l-Leucovorin (LV) therapy from January 2000 to March 2005. The RPMI regimen was employed, but 5-FU was administered at the dose of 500 mg/body for the first cycle and 750 mg/body for subsequent cycles, thanks to its safety, economy, and simplicity. l-LV was administered at 375 mg/body for all cycles. An average of 3.6 cycles were given, and the average 5-FU dose was 427.7 mg/m(2). The probability of the toxicities (Grade 3 or 4) tended to be less frequent compared with that observed in multi-center cooperative studies in Japan, although the frequency of nausea and vomiting was similar. Responses were CR 0/56, PR 16/56, NC 23/56, and PD 17/56, and the overall response rate was 28.6%. The median progression-free survival time was 6.0 months, and the median overall survival time was 14.0 months, which was longer than that achieved in multi-center studies in Japan. These data suggest that new regimens such as FOLFOX 4 and infusional 5-FU/l-LV therapy can be administered at lower doses of anti-cancer drugs with less toxicity and possible longer survival time.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Survival Rate

Pharmacokinetic modulating chemotherapy (PMC) is designed to boost high serum 5-fluorouracil (5-FU) concentrations via modulation by uracil. The aim of this study was to evaluate the efficacy of PMC as a second-line chemotherapy for postresectional recurrences of colorectal carcinoma.. Thirteen patients with unresectable recurrences of colorectal carcinoma were treated with PMC as the second-line chemotherapy, after 5-FU or its derivatives as the first-line chemotherapy. PMC was initiated with a 400 mg combination of uracil and tegafur daily and a 24-hour continuous intravenous infusion of 600 mg/m(2) 5-FU once weekly. The 5-FU dose was increased as the disease progressed.. Six (46%) of the 13 patients exhibited a partial response (PR) to PMC, based on the RECIST criteria. PR was achieved in 2 of 5, 2 of 5, and 2 of 3 patients undergoing oral administration of 5-FU derivatives, intravenous infusion of 5-FU/l-leucovorin and hepatic-artery infusion of 5-FU, respectively. The median survival time of the 13 patients was 17 months.Grade-2 toxicity was found only in 2 patients.. Because PMC is chronomodulating, it is an effective and safe treatment for recurrent colorectal carcinoma. PMC with a dose increase of 5-FU is recommended as a promising second-line regimen for unresectable colorectal carcinoma resistant to 5-FU.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chronotherapy; Colonic Neoplasms; Drug Administration Schedule; Drug Combinations; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Rectal Neoplasms; Survival Rate; Tegafur; Uracil

We report the complete response for one year of a patient with simultaneous multiple lung metastases from colon cancer who was treated using a combination of irinotecan (CPT-11) and uracil/tegafur (UFT)/Leucovorin (LV) using a schedule reported overseas. A 61-year-old woman was admitted to our hospital and diagnosed with ascending colon cancer and simultaneous multiple lung metastases. The patient underwent a right hemicolectomy and was treated with CPT-11 (150 mg/m(2)) on day 1 and oral UFT and oral LV on days 1-14. This treatment cycle was repeated every 3 weeks. A CT examination after 4 cycles of chemotherapy revealed a partial response of multiple lung metastases, and the next examination after 6 cycles revealed a complete response. The adverse effects observed during this chemotherapy regimen were leucopenia (grade 1), neutropenia (grade 2), vomiting (grade 2) and hair loss (grade 1). The patient is now receiving her 22nd cycle of chemotherapy, and her multiple metastases have shown a complete response for one year. The CPT-11 and UFT/LV combination therapy was well tolerated and was covered by the national health insurance system in Japan. This treatment may enable prolonged survival and improve quality of life in patients with metastatic colorectal cancer.

Topics: Adenocarcinoma; Alopecia; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Drug Administration Schedule; Drug Combinations; Female; Humans; Irinotecan; Leucovorin; Leukopenia; Lung Neoplasms; Middle Aged; Neoplasms, Multiple Primary; Neutropenia; Remission Induction; Tegafur; Uracil; Vomiting, Anticipatory

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Aorta, Thoracic; Bevacizumab; Camptothecin; Fluorouracil; Humans; Irinotecan; Leucovorin; Lung Neoplasms; Male; Middle Aged; Rectal Neoplasms; Thromboembolism; Tomography, X-Ray Computed

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

In Japan, cancer chemotherapy for advanced and recurrent colorectal cancer has not been adequately developed in comparison with the USA and Europe. However, the number of patients with advanced colorectal cancer has increased dramatically in this decade. Therefore, effective and feasible regimens against colorectal cancer are urgently needed. We designed a new regimen to evaluate the efficacy and feasibility of weekly low dose CPT-11 combined with 5-FU/l-LV therapy based on an RPMI regimen against advanced and recurrent colorectal cancer. Twenty patients were enrolled in this study. Weekly administration (CPT-11; 60 mg/m(2) div for 1st-line chemotherapy, 40 mg/m(2) div for 2nd-or 3rd-line chemotherapy, l-LV; 200 mg/m(2) div, 5-FU; 500 mg/m(2) iv, 3 consecutive weeks, 1-week break) was performed on an ambulatory basis. The treatment cycles were repeated every 4 weeks until disease progression and/or severe toxic events occurred. The overall response rate was 31.6% with 5.3% complete response and 26.3% partial response in addition to 42.1% with no changes beyond 3 months. These results suggested that the clinical benefit was shown in 73.7% of patients. Furthermore, median TTF (time to failure) of this regimen was 6.5 months and MST was 20.4 months, respectively. On the other hand, adverse events were restricted to grade 3 with 30.0% neutorocytopenia and 5.0% thrombocytopenia. Therefore, weekly low-dose CPT-11 combined with 5-FU/l-LV therapy seems to be extremely useful, with excellent anti-tumor effect and tolerable adverse reactions, for the treatment of advanced and recurrent colorectal cancer on an ambulatory basis.

Topics: Aged; Aged, 80 and over; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluorouracil; Hepatic Artery; Humans; Infusions, Intra-Arterial; Irinotecan; Leucovorin; Leukopenia; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Quality of Life; Rectal Neoplasms

Two metastatic colonic cancer patients were successfully treated by the combination therapy of UFT plus oral Leucovorin (UFT/LV). UFT was administered orally every eight hours at a dose of 300 mg/day in case of less than 1.20 m(2), 400 mg/day in case of between 1.20 and 1.70 m(2), 500 mg/day in case of over 1.70 m(2), and Leucovorin (75 mg/day) was simultaneously given for 28 consecutive days and stopped for seven days. This cycle was repeated until the patients requested the therapy be discontinued or a severe adverse reaction was observed. Case 1: A 79-year-old male had undergone sigmoidectomy for colonic cancer in 2001 and was diagnosed with pulmonary metastases in August, 2005. His performance status (PS) was grade 3. Case 2: A 61-year-old male with liver metastasis whose primary colonic lesion was surgically resected. After 2 cycles of UFT/LV therapy, a good partial response was achieved in both cases. Adverse effects were very mild, indicating that this therapy was very safe and recommendable for the treatment of metastatic colonic cancer patients with poor PS.

Topics: Adenocarcinoma; Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols; Colon, Sigmoid; Colonic Neoplasms; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Remission Induction; Tegafur; Uracil

A 53-year-old man, admitted for inguinal hernia, complained of body weight loss in a preoperative condition check. We examined the digestive tract and diagnosed stage IV advanced rectal carcinoma with multiple lung metastases. It caused ileus, so emergency colostomy was performed. After that his general condition recovered, and two cycles of neoadjuvant chemotherapy (NAC) by irinotecan combined with 5-fluorouracil and l-leucovorin (IFL) therapy were performed on an outpatient basis. Lung metastatic nodules disappeared. We established a diagnosis of down staging for stage IIIa, and performed a lower anterior resection with D 2 lymph node dissection to allow a curability-A resection. The pathological effect of NAC was Grade 2. Post-operatively, two cycles of IFL therapy were then performed. There has been no sign of recurrence, and no adverse effects by chemotherapy have been seen during this treatment. Thus, NAC by IFL therapy can be one of the useful treatment approaches for patients with advanced rectal cancer.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Colostomy; Drug Administration Schedule; Fluorouracil; Humans; Ileus; Irinotecan; Leucovorin; Lung Neoplasms; Lymph Node Excision; Male; Middle Aged; Neoplasm Staging; Rectal Neoplasms

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Medical Oncology; Neoplasm Staging; Organoplatinum Compounds; Radiotherapy, Adjuvant; Rectal Neoplasms

The aim of this study was to evaluate the efficacy and toxicity of 5-fluorouracil (5-FU) and l-leucovorin (I-LV) in 50 patients with advanced or recurrent colorectal cancer in our institute. The dose of 5-FU was 600 mg/m2 and the dose of l-LV was 250 mg/m2. Objective response were 36.8% of patients who had administration of full-dose and 14.8% of patients who had the administration of reduced dose or prolonged interval. No significant difference was observed in clinical benefit rates between patients administrated in full-dose and patients in reduced dose or prolonged interval. Median survival time (MST) of patients in reduced dose or prolonged interval is longer than patients in full-dose. These data suggest that 5-FU/l-LV can be given in the outpatient and yields improved prognosis and minimal adverse reactions even in patients in reduced dose or prolonged interval.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Diarrhea; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Rectal Neoplasms; Retrospective Studies; Survival Rate

In July 2003, a 59-year-old man underwent a right hemicolectomy for sigmoid colon cancer. Hepatic intraarterial injection therapy with 5-FU/CDDP was not only ineffective against a liver metastasis but a lung metastasis was also found, and therefore systemic chemotherapy with CPT-11/5-FU/l-LV (IFL) was administered. After onetime IFL therapy, the CPT-11 was withheld due to ileus. Although 5-FU/l-LV therapy was administered, it was ineffective. IFL therapy was again performed, with the dose decreased by 20%, as part of ambulatory treatment. Not only the liver metastasis but also the lung metastasis decreased significantly in size after one course. In addition, no severe adverse reactions were observed during the treatment, which enabled the therapy to be continued as part of an ambulatory regimen. The results suggest that IFL therapy is effective against colon cancer with lung/liver metastasis and can be administered as part of ambulatory treatment.

Topics: Ambulatory Care; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colectomy; Drug Administration Schedule; Fluorouracil; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymph Node Excision; Male; Middle Aged; Quality of Life; Sigmoid Neoplasms

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cholangitis, Sclerosing; Colonic Neoplasms; Combined Modality Therapy; Fatal Outcome; Fluorouracil; Humans; Leucovorin; Lung Diseases, Interstitial; Lung Neoplasms; Male; Prednisolone

Chemotherapy combining 5-fluorouracil (5-FU) with leucovorin is now used as a standard regimen for chemotherapy of inoperative, recurrent or distantly-metastasized colorectal carcinoma. We recently treated a patient with multiple metastases of sigmoid colon cancer by sigmoidectomy and oral drug therapy using a combination of Uzel (dl-leucovorin) and UFT (uracil and tegafur). Three courses of this therapy were administered, with each course consisting of treatment for 4 consecutive week (UFT 400 mg/day, Uzel 75 mg/day) and a one week interval between successive courses. The therapy resulted in marked reduction of tumor and this response was rated as PR (partial response). The lower lobe of the right lung, which showed the largest tumor (34.5 x 35.7 mm), was resected, and the upper lobe of the same lung, showing a small metastastic tumor (4.4 x 4.6 mm), was partially resected. Oral chemotherapy, which had begun before surgery, was continued after lobectomy and partial pneumonectomy. To date (January 15, 2005), the patient has received 5 courses of this therapy and has shown no signs of tumor exacerbation. Because this therapy has allowed satisfactory control of metastatic tumor for about one year since surgery without causing any adverse reaction or requiring re-hospitalization, it is fair to say that the therapy has successfully maintained the quality of life (QOL) of this patient.

Topics: Antineoplastic Combined Chemotherapy Protocols; Colon, Sigmoid; Drug Administration Schedule; Drug Combinations; Female; Humans; Leucovorin; Lung Neoplasms; Middle Aged; Pneumonectomy; Quality of Life; Sigmoid Neoplasms; Tegafur; Uracil

We encountered a patient with metastatic disease of the lung from oropharyngeal cancer who achieved a complete response to 3 cycles of chemotherapy with docetaxel, cisplatin, 5-FU and l-leucovorin (TPFL). A 72-year-old man was found to have metastatic disease of the lung 32 months after treatment of oropharyngeal squamous cell carcinoma. Chemotherapy was initiated with TPFL and the patient obtained a complete response after 3 cycles. Twelve months after chemotherapy he had no recurrence. We conclude that the use of docetaxel cisplatin, 5-FU and l-leucovorin for metastatic squamous cell carcinoma of the head and neck is a viable option.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Docetaxel; Drug Administration Schedule; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Oropharyngeal Neoplasms; Remission Induction; Taxoids

A 58-year-old man who had colon cancer with liver and multiple lung metastases underwent ileocecal resection on May 10, 2002. MTT assay of 5-FU and CPT-11 was performed with resected material, with both medicines accepted for sensitivity. On June 4, he received combination chemotherapy with CPT-11 + 5-FU/l-LV. The liver metastasis disappeared and was judged CR from a CT of the abdomen. Almost all the multiple lung metastases had disappeared or were decreased in size. They were therefore judged NC from a CT of the chest. Moreover, CEA and CA19-9 decreased to within normal limits. While he was receiving bimonthly chemotherapy with only CPT-11 as a maintenance therapy, liver and lung metastases did not change. Combination chemotherapy with CPT-11 + 5-FU/l-LV is effective. The anticancer drug sensitivity examination is only one index, however. Considering adverse effects and medical costs, individualized therapy based on the sensitivity test for anticancer drugs should be performed.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Drug Administration Schedule; Drug Screening Assays, Antitumor; Fluorouracil; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Tumor Cells, Cultured

Topics: Adenocarcinoma; Aged; Carcinoma, Small Cell; Female; Humans; Intestinal Neoplasms; Leucovorin; Lung Neoplasms

Ten cases of advanced and metastatic colorectal cancer treated with irinotecan plus fluorouracil and l-leucovorin systemic chemotherapy (CPT-11/5-FU/l-LV) were investigated. The 10 patients consisted of 7 males and 3 females with a mean age of 64.3 years. We diagnosed adenocarcinoma of the colon in 2 patients and of the rectum in 8 patients. Five patients had liver and lung metastases, 1 had lymph node metastases, 1 had bone marrow metastases and 3 had recurrence in a pelvic lesion. All patients underwent 3-week chemotherapy regimen (CPT-11 50 mg/m2/week + 5-FU 400 mg/m2/week + l-LV 20 mg/m2/week). Five patients received this regimen as a first-line chemotherapy and the other patients as a second-line chemotherapy after 5-FU/l-LV chemotherapy. The effect was CR or PR in all patients receiving the regimen as a first-line chemotherapy. The progression free survival time was 6.8 months and mean survival time was 10.0 months in the first-line patients. Otherwise, all second-line patients had PD. The suppression of white blood cells (grade 1 or 2) was seen in 4 patients. All patients were able to receive the systemic chemotherapy in the outpatient setting. CPT-11/5-FU/l-LV chemotherapy appears to be an effective first-line chemotherapy for advanced and metastatic colorectal cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Leukopenia; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Retrospective Studies; Treatment Outcome

The patient was a 70-year-old man who had sigmoid colon cancer with multiple lung and paraaortic lymph node metastases. Sigmoidectomy was performed on August 3, 2001. After the operation, combined l-Leucovorin (LV) + 5-fluorouracil (5-FU) was carried out. As a result, lung and lymph node metastases were reduced markedly and CEA level decreased. It is suggested that this combination therapy may be useful for advanced colon cancer patients.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Drug Administration Schedule; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Lymphatic Metastasis; Male; Tomography, X-Ray Computed

The aim of the present study was to establish the accurate cutoff points of post-treatment serum beta-hCG values in identifying chemotherapeutic refractory cases among patients with low-risk persistent trophoblastic disease (PTD) treated with 8-day methotrexate-folinic acid as the primary therapy.. The values of serum beta-hCG measured before initiating treatment and weekly thereafter in 26 patients with low-risk PTD undergoing 8-day methotrexate-folinic acid treatment were analyzed. Thereafter, we determined the weekly cutoff points to identify the patient refractory for treatment by means of receiver-operating characteristic (ROC) plots analysis.. The values of cutoff points in the pretreatment, the post-treatment 1st, 2nd, 3rd, and 4th week were 18.6, 15.0, 5.4, 3.4, and 2.0 ng/ml, respectively, and the value of accuracy during these weeks was appropriate (> 80%). When using the cutoff points of one and two weeks after initiating treatment, the accuracy in identifying chemotherapeutic refractory patients was 87.5% and 88.0%, respectively, with the highest values exceeding 85%. The sensitivity and specificity at one week were 92.9 and 80.0%, respectively. Similarly, the sensitivity and specificity at two weeks were 93.3 and 80.0%, respectively.. These results suggest that the cutoff points of one and two weeks after initiating treatment are useful in identifying chemotherapeutic refractory patients among low-risk PTD patients, receiving 8-day methotrexate-folinic acid treatment.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Chorionic Gonadotropin; Female; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Pregnancy; Reference Values; Sensitivity and Specificity; Treatment Outcome; Trophoblastic Neoplasms; Uterine Neoplasms

We report a case of irinotecan-resistant colon cancer responding to chronotherapy with oxaliplatin (L-OHP), 5-FU, l-LV (l-Leucovorin). A 72-year-old man was examined at a certain hospital because of constipation and appetite loss. Chest computed tomography (CT) revealed lung metastases, and abdominal CT revealed liver metastases. He was then referred to our hospital. A colonoscopy revealed type 2 tumor in the colon, at the hepatic flexure. We diagnosed adenocarcinoma of the colon with metastases to the liver and lung. Resection of the primary lesion was performed, and chemotherapy consisting of systemic administration of CPT-11, 5-FU and l-LV was performed. After 2 courses of combined treatment with CPT-11/5-FU/l-LV, CT revealed considerable reduction of the metastatic tumors. However, after 3 courses of combined treatment, progressive disease was observed and new brain and bone metastases were detected. We imported and used a non-approved/pending drug, oxaliplatin from the Remedy and Health Corporation, with informed consent from the patient and his family and our clinical ethics committee. Chronotherapeutic schedules have been performed, from which the safety and activity of oxaliplatin against advanced colorectal cancer was reported. Our patient received a 5-day course of chronomodulated 5-FU and l-LV (750 and 300 mg/body/day, respectively; peak delivery rate at AM 4:00 hours) with L-OHP on the first day of each course (100 mg/body, as a 6-hour infusion). Each course was again repeated every 21 days. A partial response was observed in the liver and lung metastases. These results indicate that chronomodulated 5-FU and LV with L-OHP therapy could be an effective regimen for cases of irinotecan-resistant colon cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Camptothecin; Chronotherapy; Colonic Neoplasms; Drug Evaluation; Drug Resistance, Neoplasm; Fluorouracil; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Organoplatinum Compounds; Oxaliplatin

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Chemotherapy, Adjuvant; Colectomy; Colonoscopy; Fluorouracil; Gastrointestinal Hemorrhage; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Palliative Care; Sigmoid Neoplasms; Tomography, X-Ray Computed

A 49-year-old man was hospitalized because of a 2-month history of purpura in his extremities and for back pain. Laboratory findings showed alkaline phosphatase to be greatly elevated, and platelet counts and coagulation factor showed that the patient had disseminated intravascular coagulation (DIC). Compression fractures of the thoracic vertebrae were found on radiological examination. The histological findings from bone marrow showed metastasis of adenocarcinoma with signet-ring cells, although the primary site was unknown. To reduce tumor cells in number and improve DIC, 11 cycles of 5-Fluorouracil and leucovorin therapy were done, and the patient survived for 12 months. Autopsy showed a 0.8 cm diameter, poorly differentiated adenocarcinoma with the signet-ring cell type in the lamina propria of the Vater's ampulla. Many metastatic foci and micro tumor emboli were found in the lung and in bone marrow. The sections of the stomach, the gallbladder, urinary bladder, prostate, and thyroid gland showed no malignant cells. These findings suggest that the origin of the cancer may have been located in the Vater's ampulla. This is a rare case of an ampullary tumor of poorly differentiated adenocarcinoma with the signet-ring cell type, without jaundice but with multiple metastasis. 5-Fluorouracil and leucovorin were effective for increasing survival time and improving quality of life.

Topics: Ampulla of Vater; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Neoplasms; Carcinoma, Signet Ring Cell; Common Bile Duct Neoplasms; Disseminated Intravascular Coagulation; Fatal Outcome; Fluorouracil; Humans; Jaundice; Leucovorin; Lung Neoplasms; Male; Middle Aged; Neoplastic Cells, Circulating; Quality of Life

5 patients with colorectal cancer with multiple liver metastases underwent resection of primary lesions. We then evaluated the effects of hepatic arterial infusion chemotherapy with low-dose leucovorin and 5-FU. Weekly, dl-leucovorin of 30 mg/body or l-leucovorin of 25 mg/body was administered as a bolus, then 5-FU of 500 mg/body was administered for 1 hour through the hepatic artery from the subcutaneous reservoir on an outpatient basis. 2 of 5 patients achieved a CR of liver metastases, but later 1 of these 2 cases had metastases of bone and lung. No adverse effects, such as nausea, vomiting, diarrhea or bone marrow suppression, were seen after this treatment in any of the patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Colorectal Neoplasms; Drug Administration Schedule; Drug Evaluation; Fluorouracil; Hepatic Artery; Humans; Infusion Pumps, Implantable; Infusions, Intra-Arterial; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged

One patient with pulmonary metastasis from colon cancer and one with para-aortic lymph node metastasis were treated with a combination of irinotecan and UFT. Irinotecan (100 mg/m2) was given by 24-hour intravenous infusion on day 1, and UFT (600 mg/day) was given orally on days 3 to 7 and days 10 to 14 of a 2-week course, which was then repeated. In the patient with pulmonary metastasis, the lesions in the lung resolved after 7 courses of chemotherapy. Surgery was performed after 10 courses. The patient with para-aortic lymph node metastasis had a partial response after 4 courses of chemotherapy, and underwent surgery after 6 courses. The only adverse effects were grade 2 myelosuppression and hair loss, none of which were severe enough to require treatment. With this chemotherapy regimen, patients are admitted for two days biweekly for 24-hour intravenous infusion of CPT-11. Thus, most of the treatment can be performed on an outpatient basis. The combination of irinotecan and UFT is expected to be useful for metastatic or recurrent colon cancer.

Topics: Adenocarcinoma; Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colectomy; Colonic Neoplasms; Combined Modality Therapy; Drug Administration Schedule; Fluorouracil; Humans; Irinotecan; Leucovorin; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Tegafur; Uracil

A 48-year-old male patient was admitted to our institution with left hypochondralgia. Preoperative serum CEA was 504 ng/ml. Under a radiological diagnosis of simultaneous double cancer of the pancreas and lung, resection was performed. Pathological study revealed primary pancreatic cancer with lung metastasis. After the operation, serum CEA fell to 55 ng/ml. Seventeen months later, bowel obstruction occurred and serum CEA was 140 ng/ml. One course of systemic chemotherapy, using the combination of CDDP, 5-FU and Leucovorin, was successful. After another three months, however, the same clinical symptoms occurred. With no response to the prior chemotherapy regimen, surgery was undertaken and a mass at the mesentery was removed. Fifty-nine months have passed since the initial operation and the patient is free of disease, though his serum CEA is around 50 ng/ml. In conclusion, there are cases of pancreatic cancer in which tumor dormancy can be achieved by postoperative 5-FU based chemotherapy.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carcinoembryonic Antigen; Cisplatin; Combined Modality Therapy; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Pancreatectomy; Pancreatic Neoplasms; Pneumonectomy

Thirty-two women with untreated metastatic breast cancer were treated with 100 mg/M2 i.v. methotrexate (MTX), 600 mg/M2 5-fluorouracil (5FU) and leucovorin 15 mg orally every 6 hr, 24 hr after MTX (MFL) on days 1 and 8 every 28 days. Stratification was according to sites of metastases (mets), adjuvant (adj), chemotherapy (CTX), and/or hormonal therapy or no adj therapy (Tx). Treatment continued until documented radiographic or clinical disease was in progression. Toxicity was mild, consisting of only minimal elevations of transaminases and mild cytopenias. There was no pulmonary toxicity. There were no hospitalizations, treatment delays or cessations for toxicity. One patient with skeletal mets had a complete response and 7 had partial responses. The overall median progression free survival (PFS) was 13.8 months (mos). Eighteen patients with skeletal mets had PFS from 7-70 mos (median 15.9). Five patients with lung mets only had PFS from 6-20 mos (median 9.8 mos). Patients with liver alone or with other visceral mets showed progression within 2-5 mos. However, patients with bone and visceral mets without liver involvement had PFS from 8-50 mos (median 20.5). Of 21 adj Tx failures the median PFS was 8.8 mos (2-94). Six who received adj CTX had a median PFS of 7.6 mos (3-12) and 4 tamoxifen (tam) failures a median PFS of 11 mos (8-15). Eleven patients who received adj CTX+tam had a median PFS of 8.5 mos (2-94). Six patients received tam at adj failure and MFL at progression. These six had a median PFS of 19.8 mos (8-50). The patients (six, who received no prior adj Tx) had a median PFS of 24.3 (8-70). MFL is as effective in achieving clinical remissions in metastatic breast cancer, is inexpensive and is far less toxic than other CTX regimes. MFL should strongly be considered as first line Tx.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Brain Neoplasms; Breast Neoplasms; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Middle Aged; Mitoxantrone; Prospective Studies

Recent investigations have focused on the prognostic value of thymidylate synthase (TS) assessment in metastases of colorectal carcinoma (CRC). In order to evaluate the prognostic impact of TS expression after resection of metastases of colorectal cancer followed by systemic adjuvant chemotherapy, we performed an immunohistochemical characterisation of TS in the primary tumours and in the corresponding radically resected hepatic and pulmonary metastases. An additional objective was to compare the levels of TS in primary and metastatic disease. TS expression was assessed by immunohistochemistry using the monoclonal antibody TS 106. The study population consisted of 60 patients: 48 underwent liver and 12 lung resection. All of them received adjuvant chemotherapy after metastasectomy according to the Mayo Clinic schedule. In the 49 evaluable primary tumours, TS score was high in 53% and low in 47% of patients, while in the 60 metastatic samples TS immunostaining was high in 33% and low in 67%. There was a significantly smaller number of high TS expressors in metastatic than in primary tumours (P<0.04). No correlation was observed between TS expression and the site of the metastasis. TS status did not significantly correlate with the median disease-free interval (DFI) after metastasectomy, although this parameter was longer for patients with low TS immunoreactivity in the resected metastases than for those with high TS lesions (19.6 versus 13.8 months). Patients with high TS levels, however, had a significantly shorter median overall survival (OS) (27.6 months) than those with low TS expression (36.3 months) (P<0.008). TS status in the resected metastases confirmed its independent prognostic value in the multivariate analysis and was the only prognostic marker of OS in the subgroup of patients with resected liver metastases. These results suggest that high TS levels in resected metastases of colorectal cancer are associated with a poor outcome after surgery and 5-FU adjuvant therapy; therefore, a prospective assessment of TS levels in resected colorectal metastases could be useful to define which patients will most likely benefit from 5-FU adjuvant therapy after metastasectomy. Chemotherapeutic agents that target TS may not be the appropriate adjuvant treatment after metastasectomy for patients with a high TS expression in the resected metastases of colorectal cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Chemotherapy, Adjuvant; Colorectal Neoplasms; Disease-Free Survival; Female; Fluorouracil; Follow-Up Studies; Humans; Immunohistochemistry; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Prognosis; Thymidylate Synthase

Folates, components of the B-complex vitamins, have numerous pharmacological effects. In oncology combining folates with 5-fluorouracil (5-FU) enhances the cytotoxic effects of chemotherapy in colon cancer patients. Folic acid has been rarely involved in adverse allergic reactions. To the best of our knowledge no anaphylactic reaction secondary to folinic acid (FA) administration has ever been reported before.. An 80-year-old patient had adjuvant chemotherapy for colon cancer including FA and 5-FU and irinotecan as a second line agent after multiple metastases.. Following FA administration anaphylactic shock occurred. Diagnosis was made according to the French method of adverse reactions monitoring.. Anaphylactic shock may be an adverse reaction of FA in patients receiving chemotherapy for colon cancer.

Topics: Aged; Aged, 80 and over; Anaphylaxis; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Fluorouracil; Humans; Injections, Intravenous; Irinotecan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Treatment Outcome

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Chills; Fever; Fluorouracil; Humans; Hypotension; Infusions, Intravenous; Leucovorin; Lung Neoplasms; Male; Middle Aged; Nausea; Organoplatinum Compounds; Oxaliplatin; Rectal Neoplasms; Vomiting

The response to chemotherapy of solid tumors is generally assessed by measuring tumors visualized by imaging. However, the response assessment based on imaging is not always feasible because patients often have disease not measurable by imaging, such as diffuse peritoneal dissemination. We evaluated the correlation between the change on imaging and change in CEA levels for assessing chemotherapeutic response of patients with metastatic colorectal cancer. Between July 1993 and August 1999 we retrospectively examined 136 patients with metastatic colorectal carcinoma, all of whom had measurable lesions. Forty patients received oral tegafur-uracil (300 mg/m2/day) plus folinic acid (60 mg/day) for 4 weeks, repeated every 5 weeks, as the firstline treatment. Another 96 patients received either a weekly intravenous bolus injection of 5-fluorouracil (400 mg/m2) plus folinic acid (20 mg/m2), or an intravenous bolus injection of 5-fluorouracil (425 mg/m2) plus folinic acid (20 mg/m2) for 5 consecutive days every month. Responders, based on CEA assessment, were defined as those with a greater than 50% drop in CEA level for more than 4 weeks. The pretreatment CEA levels were elevated beyond the normal cutoff value in 110 (81%) patients. A response rate of 18.4% (95% CI, 11.9-24.9%), including 8 complete remissions and 17 partial remissions, was achieved according to imaging studies. The response rate assessed by CEA was 25% (34/136). Sixteen responders (47%) based on CEA had no remission on imaging. The sensitivity of change in CEA levels in the prediction of true responders and progressive diseases on imaging were 72% and 81%, respectively. In terms of the positive predictive value, change in CEA levels in the prediction of true responders and progressive disease on imaging were 53% and 85%, respectively. Patients with remarkable falls on CEA levels survived significantly longer than nonresponders (P < 0.001, log-rank test). At follow-up of 48 months the median survival for responders and nonresponders assessed by CEA was 28 months and 13 months, respectively. These data suggest that measurement of CEA levels might be helpful in monitoring chemotherapeutic response when imaging study is unsuitable for assessing the response in clinical practice. Furthermore, measurement of CEA levels may be helpful in determining the prognosis of patients with metastatic colorectal cancer receiving chemotherapy.

Topics: Adult; Aged; Biomarkers, Tumor; Carcinoembryonic Antigen; Chemotherapy, Adjuvant; Colectomy; Colorectal Neoplasms; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Monitoring, Physiologic; Probability; Prognosis; Retrospective Studies; Sensitivity and Specificity; Survival Analysis; Treatment Outcome

We attempted a new regimen of intermittent administration of 5-FU and low-dose Isovorin (F.I) to four patients with advanced and recurrent colon cancer. A partial response (PR) was achieved in two of four patients who had evaluable lesions for this treatment. We observed few side effects among these patients. Only one patient among four showed grade 1 neuropathy after two administrations of this chemotherapy. However, after a two-week pause in administration, the neuropathy disappeared and we could continue the therapy. This patient with multiple liver metastases achieved a partial response. Other patients had no side effects such as bone marrow suppression or digestive symptoms. This intermittent F.I treatment might be an effective and promising therapy with few side effects even for patients with poorer conditions.

Topics: Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local

The aim of the study was to initiate a search for factors which might independently predict the need for salvage therapy in patients with low-risk gestational trophoblastic tumor.. The independent effect of six factors on the need for salvage chemotherapy was assessed in patients with low-risk gestational trophoblastic tumor who were treated with low-dose methotrexate and folinic acid. The accuracies of World Health Organization and Charing Cross Hospital scores were also compared.. Age, pretreatment beta hCG, antecedent pregnancy-treatment interval, and the presence of chest metastases detected on chest X ray were not significantly predictive. The size of tumor (P = 0.001) and the presence of chest metastases on chest computerized tomography (P = 0. 00028) had independent, statistically significant predictive power, and a simple prognostic index was derived from these variables. The World Health Organization score was found to be significantly better than the Charing Cross Hospital score. The accuracy of the simple prognostic index was slightly greater than that of the World Health Organization score, although this was not statistically significant.. These results confirm that patients entered into studies of different therapies for low-risk gestational trophoblastic tumor should be stratified and that a simple score, derived from the results of tumor size and chest computerized tomography, is potentially as good as the World Health Organization score for predicting the need for salvage therapy.

Topics: Adolescent; Adult; Age Factors; Antineoplastic Combined Chemotherapy Protocols; Chorionic Gonadotropin, beta Subunit, Human; Clinical Trials as Topic; Female; Humans; Leucovorin; Logistic Models; Lung Neoplasms; Methotrexate; Middle Aged; Practice Guidelines as Topic; Predictive Value of Tests; Pregnancy; Prognosis; Risk Factors; ROC Curve; Salvage Therapy; Severity of Illness Index; Time Factors; Tomography, X-Ray Computed; Trophoblastic Neoplasms

Cancer cell lines in standard cell culture medium or in animal models are surrounded by an environment with relatively high folate (HF) levels, compared with folate levels in human plasma. In the present study we adapted 4 colon cancer (C26-A, C26-10, C26-G and WiDr) and 3 squamous cell carcinoma of the head and neck (HNSCC) cell lines (11B, 14C and 22B) to culture medium with low folate (LF) levels (2.5, 1.0 and 0.5 nM, respectively) and investigated whether folate depletion had an effect on sensitivity to antifolates and which mechanisms were involved. All LF cell lines showed a higher sensitivity to 5-fluorouracil (5-FU) alone or in combination with leucovorin (LV) (2-5-fold), to the thymidylate synthase (TS) inhibitors, AG337 (2-7-fold), ZD1694 (3-49-fold), ZD9331 (3-40-fold), LY231514 (2-21-fold) or GW1843U89 (4-29-fold) or to the dihydrofolate reductase (DHFR) inhibitor PT523 (2-50-fold) compared with their HF variants cultured in standard medium containing up to 8 microM folic acid. LV could only increase sensitivity to 5-FU in HNSCC cell lines 14C and 14C/F. The differences in sensitivity could partially be explained by a 2-7-fold increased transport activity of the reduced folate carrier (RFC) in LF cell lines, whereas no significant change in folylpolyglutamate synthetase (FPGS) activity was observed. Furthermore, the protein expression and catalytic activity of the target enzyme TS were up to 7-fold higher in HF colon cancer cells compared with the LF variants (p < 0.05). Although the TS protein expression in LF HNSCC cells was also lower than in HF variants, the TS catalytic activity and FdUMP binding sites were up to 3-fold higher (p < 0.05). Thus, changes in TS levels were associated with differences in sensitivity. These results indicate that folate depletion was associated with changes in TS and RFC levels which resulted in an increase in sensitivity to 5-FU and antifolates. The folate levels in LF medium used in this study are more representative for folate levels in human plasma and therefore these data could be more predictive for the activity of 5-FU and antifolates in a clinical setting than results obtained from cell lines cultured in HF medium or in animal models.

Topics: Animals; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Carrier Proteins; Colonic Neoplasms; Fluorouracil; Folic Acid; Folic Acid Antagonists; Head and Neck Neoplasms; Humans; Leucovorin; Lung Neoplasms; Membrane Proteins; Membrane Transport Proteins; Mice; Multienzyme Complexes; Neoplasms; Peptide Synthases; Reduced Folate Carrier Protein; Tetrahydrofolate Dehydrogenase; Thymidylate Synthase; Tumor Cells, Cultured

The addition of oxaliplatin (L-OHP) to a 5-fluorouracil (5-FU)/ leucovorin (FA) regimen was retrospectively evaluated in 35 consecutive advanced colorectal cancer patients after progression of disease. L-OHP, 25 mg/m2/day, was infused from 10.00-22.00 with a peak flow at 16.00 while 5-FU, 700 mg/m2/day and FA, 150 mg/m2/day of the I-form or 300 mg/m2/day of the racemic form, from 22.00 to 10.00 with a nocturnal peak at 4.00, for 5 days every 3 weeks in 24 patients and for 4 days every 2 weeks in the other 11. Diarrhea and sensitive neuropathy were the most relevant types of toxicity (17% of patients). An objective response was achieved in 8/35 patients (23%) [95% CL 9-37], stabilization in 15 patients (43%) which included five minor responses, and progression in 12. There was no relevant difference in quality of life assessed with the EORTC QLQ C30+3 questionnaire before and after treatment. Median duration of response and median progression-free survival were 6 months; median overall survival was 11 months. This retrospective study showed that it is possible to reverse resistance to chronomodulated 5-FU by adding chronomodulated L-OHP to the previous regimen; comparison with different schedules of this combination should be performed in order to identify the best tolerated and active regimen as second-line treatment of advanced colorectal cancer.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Chronotherapy; Colorectal Neoplasms; Drug Resistance; Drug Resistance, Neoplasm; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Quality of Life; Retrospective Studies; Surveys and Questionnaires

Lymphoepithelioma-like carcinoma (LELC) of the lung, an Epstein-Barr virus-associated undifferentiated carcinoma, is a rare entity of pulmonary malignancy. It tends to affect young non-smoking Asians and is often resectable. However, little is known of the treatment of the even rarer locally advanced or metastatic cases. We report our experience of three Chinese patients with advanced LELC of the lung who were treated with combination-chemotherapy (5-fluorouracil, leucovorin, and cisplatin) and radiotherapy. The encouraging response of these patients supports the use of this regime in other patients.

Topics: Adult; Antimetabolites, Antineoplastic; Antineoplastic Agents; Carcinoma; Cisplatin; Female; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Prospective Studies; Tomography, X-Ray Computed; Treatment Outcome

There is currently no method to cure patients with disseminated colorectal cancer, which is the third leading cancer killer in the Western World. This report shows that the GW-39 intrapulmonary micrometastatic human colonic cancer model in nude mice can be cured with radiolabeled antibodies against carcinoembryonic antigen, and that this approach of radioimmunotherapy is superior to conventional chemotherapy with 5-fluorouracil and leucovorin (5-FU/LV). Monovalent Fab fragments labeled with 131I are superior to intact IgG when survival was evaluated 3, 7, and 14 days after implantation, leading to cures in up to 90% of the mice. Histological results provide support for the differences in therapeutic efficacy observed. Microautoradiography was used to evaluate the intratumoral distribution of each form of antibody. The enhanced tumor control by Fab compared with IgG could be explained in part by the homogeneity of radioantibody distribution of Fab. Biodistribution analysis and initial dose rate calculations for all three forms of antibody also help explain the ability of 131I-labeled Fab to provide better tumor growth control than seen with 131I-labeled IgG. Thus, radioimmunotherapy may be a new modality to treat metastatic disease, particularly when using small antibody fragments.

Topics: Animals; Antibodies, Monoclonal; Antimetabolites, Antineoplastic; Bone Marrow Transplantation; Carcinoembryonic Antigen; Colonic Neoplasms; Fluorouracil; Humans; Immunoglobulin Fragments; Immunoglobulin G; Iodine Radioisotopes; Leucovorin; Lung Neoplasms; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Metastasis; Neoplasm Transplantation; Radioimmunotherapy; Radiometry; Time Factors; Tumor Cells, Cultured

Many studies connected with different aspects of the quality of life (QL) have been increasingly reported. In this study we have been used FACT questionnaire to estimate QL in three groups of cancer patients receiving chemotherapy. Questionnaires were completed by 177 patients. Adverse effects of treatment severely influence the cancer patients QL. The most significant worsening of QL was noticed in the group of lung cancer patients receiving the most emetogenic chemotherapy(i.e. cis-platinum, vepesid). In other two groups (gastric and colorectal cancer patients) side effects of chemotherapy caused relatively less QL deterioration. This finding implicates possibility of intensifying the course of treatment (dosage and duration) assuming there is no hematopoetic insufficiency.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Cisplatin; Colorectal Neoplasms; Epirubicin; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Neoplasms; Quality of Life; Stomach Neoplasms; Surveys and Questionnaires

In the UK there are standardized surveillance procedures for gestational trophoblastic disease. However, there are differences in practice between the two treatment centres in terms of definition of persistent gestational trophoblastic disease, prognostic risk assessment and chemotherapeutic regimens. The role of prophylactic chemotherapy for cerebral micrometastatic disease in persistent gestational trophoblastic disease is unclear. We have analysed the outcome of 69 patients with lung metastases who elsewhere might have received prophylactic intrathecal chemotherapy. Of the 69 patients, 67 received intravenous chemotherapy only. The other two patients had cerebral metastases at presentation. One patient who received only intravenous chemotherapy subsequently developed a cerebral metastasis, but this patient's initial treatment was compromised by non-compliance. This experience supports our current policy of not treating patients with pulmonary metastases, without clinical evidence of central nervous system (CNS) involvement, with prophylactic intrathecal therapy.

Topics: Adolescent; Adult; Antidotes; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Dactinomycin; Etoposide; Female; Follow-Up Studies; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Middle Aged; Patient Compliance; Pregnancy; Prognosis; Retrospective Studies; Risk Assessment; Trophoblastic Neoplasms; Uterine Neoplasms

We report a rare complication of a secondary malignant solid tumor in two patients with non-Hodgkin's malignant lymphoma who developed lung adenocarcinoma after treatments with combination chemotherapies. The first was a case of primary malignant lymphoma of the cervical spinal cord which had been previously treated with radiation to the spinal lesion and combination chemotherapies and entered complete remission. The patient was further treated for relapse with autologous bone marrow transplantation preconditioned with high-dose chemotherapy. Lung adenocarcinoma developed 5.5 years after the initial diagnosis. The second case of malignant lymphoma of lymph nodes did not respond to conventional combination chemotherapies and did not enter remission. Lung adenocarcinoma developed 1 year after the initial diagnosis. The two patients died of lung carcinoma. The clinical profiles of these cases are presented and the causal relationship of primary malignant neoplasms to the second malignant neoplasms is discussed.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Cyclophosphamide; Cytarabine; Dexamethasone; Doxorubicin; Drug Administration Schedule; Female; Humans; Leucovorin; Lung Neoplasms; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Neoplasms, Second Primary; Prednisone; Spinal Cord Neoplasms; Vincristine

Many different cisplatin-based regimens have been used on advanced non-small cell lung cancer (NSCLC) in previous studies but there have been few such references in Taiwan. In this study, we evaluated the efficacy and toxicity of two different regimens including 5-Fluorouracil, Leucovorin, Etoposide and cisPlatin (FLEP) and cisPlatin, Etoposide and Mitomycin (PEM) in the treatment of patients with advanced NSCLC.. We retrospectively analyzed the records of 44 patients with NSCLC who met the selection criteria from February 1995 through April 1998. All of them were confirmed, using histologic tests, that they were in advanced stages, i.e. stage IIIB or IV. Twenty-two patients received FLEP and 22 patients received PEM.. Three patients with FLEP therapy and 3 patients with PEM therapy had partial response. No patient had complete response. The response rate was 13.6% in both groups, respectively. The median survival was 160 +/- 30 (median + SD) days for patients with FLEP therapy and 263 +/- 104 days for patients with PEM therapy. The factors that were associated with longer survival in all patients included response (Stable Disease vs Disease Progression p = 0.004, Partial Response vs Disease Progression p = 0.047) and regimen of chemotherapy (PEM vs FLEP p = 0.008). The major clinically significant toxicity was myelosupression.. The responses to regimens, FLEP and PEM, were low in our study groups that might be due to the low dose of cisplatin and etoposide in our regimens. The patients with response to chemotherapy and PEM therapy had longer median survival than those who underwent FLEP therapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Epirubicin; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Mitomycin; Retrospective Studies; Survival Rate

Facial metastasis from colorectal carcinoma is extremely rare. Only two cases have been reported in the literature. This is the first reported case of malar metastasis from colon carcinoma. The patient was a 64-year-old, white woman who underwent a low anterior resection for a nearly obstructive carcinoma at 20 cm. Her chest X-ray revealed lung metastases. Postoperatively she was treated with fluorouracil and leucovorin. Twenty months later, she presented with left facial edema, which progressively increased in size. CT scan and magnetic resonance imaging with gadolinium showed a large soft tissue mass centered about the left anterior zygomatic arch. The platysma muscle was displaced laterally, and the masseter muscle was involved. There was extension into the masticator space and bony involvement of the zygomatic arch. True-cut biopsy of the left cheek revealed metastatic adenocarcinoma. Histology was similar to that of the primary rectal adenocarcinoma. Metastasis to the malar region is extremely rare. It is a grave prognostic sign, as it is associated with advanced terminal disease. Because of the widespread metastases, only palliative treatment can be provided.

Topics: Adenocarcinoma; Antidotes; Antimetabolites, Antineoplastic; Colonic Neoplasms; Fatal Outcome; Female; Fluorouracil; Follow-Up Studies; Humans; Intestinal Obstruction; Leucovorin; Lung Neoplasms; Middle Aged; Palliative Care; Rectal Neoplasms; Skull Neoplasms; Zygoma

Between January 1994 and November 1995, 41 patients with metastatic colorectal carcinoma were enrolled in this study. All these patients had recurrent disease after a prior 5-fluorouracil based adjuvant chemotherapy or failed to achieve response by prior chemotherapy that included 5-fluorouracil. 5-Fluorouracil, 2600 mg/m2, was administered concurrently with 100 mg/m2 leucovorin over 24 hours of continuous intravenous infusion. The treatment was repeated every week until progressive disease was documented. Forty-one patients received a total of 810 courses of treatment. The overall response rate was 17.1% (95% confidence interval 5.6-28.6%). In two patients who achieved complete response, the liver was the metastatic site. The median survival was 18.4 months for responders and 12.6 months for non-responders. Gastrointestinal toxicities including diarrhea, stomatitis, nausea and vomiting were the major side-effects. Sixteen incidences (39.0%) of grade 2-3 gastrointestinal toxicities were observed. One patient (2.4%) developed a grade 3 cardiac toxicity, and another one (2.4%) had a grade 2 neurotoxicity. Hematological toxicities were minimal with no evidence of severe (grade 2 or more) leukopenia or thrombocytopenia. We conclude that in patients with pretreated metastatic colorectal cancer, weekly 24-hour infusion of high-dose 5-fluorouracil and leucovorin is associated with higher efficacy and tolerable toxicity. This regimen is a good option as a second-line treatment for those whose diseases are recurrent from or refractory to prior 5-fluorouracil, and deserves a longer period of follow-up.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Rectal Neoplasms; Survival Analysis

Either folic or folinic acid enhanced the antimetastatic activity of recombinant murine interferon beta (rMulFN beta) toward highly metastatic colon carcinoma 26 (Co 26Lu). Folinic acid administered with rMuIFN beta markedly increased asialoGM1+CD4+ and asialoGM1+CD8+ T cell production in the peritoneal cavity but not in the thymus and spleen. Peritoneal cells expressed killing activity toward Co 26Lu cells in vitro. In athymic nude mice, the above combination produced many asialoGM1+CD4+ and few asialoGM1+CD8+ T cells in the peritoneal cavity, but did not decrease lung metastatic colonies. AsialoGM1+CD4+ T cells would thus appear to have no or only very weak killing activity toward these tumor cells. The antimetastatic activity of folinic acid with rMuIFN beta was significantly decreased with anti-asialoGM1 and anti-CD8 antibodies. Inactivated CD8+ and asialoGM1+ cells cease to have killing activity toward Co 26Lu cells as shown by Winn's assay. AsialoGM1+CD8+ cell production was markedly induced in the peritoneal cavity by treatment with rMuIFN beta and folinic acid. AsialoGM1+CD8+ T cells may be inhibiting lung metastasis of Co 26Lu. Folinic acid and interferon are used in combination therapy with 5-fluorouracil for biochemical modulation. Folinic acid with interferon, as adjuvant therapy, may promote the induction of CD8+ T cell production with consequent prevention of metastasis.

Topics: Animals; Antineoplastic Agents; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Colonic Neoplasms; Drug Combinations; Folic Acid; G(M1) Ganglioside; Interferon-beta; Leucovorin; Lung Neoplasms; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Peritoneal Cavity

For previously treated advanced breast cancer, there is no standard second-line therapy. Combination chemotherapy with mitoxantrone, high-dose 5-fluorouracil (5-FU) and leucovorin (MFL regimen) had been reported as an effective and well tolerated regimen. From October 1993 to November 1995, we treated 13 patients with previously chemotherapy-treated metastatic breast cancer by mitoxantrone, 12 mg/m2, on day 1 and continuous infusion of 5-FU, 3000 mg/m2, together with leucovorin, 300 mg/m2, for 48 h from day 1 to 2. Each course of chemotherapy was given every 4 weeks. Most of these patients had more than two metastatic sites, with lung metastasis predominant. Seven patients had been treated with anthracycline. Seven patients had previously received radiotherapy and seven had received hormone therapy. Median number of courses of MFL regimen given was six and the median cumulative dose of mitoxantrone was 68.35 mg/m2. One patient had complete response, seven had stable disease, none had partial response and five had progressive disease. The overall objective response rate was 7.6%. The median follow-up period was 14 months. Median survival was 16 months. Median progression-free survival was 5 months. A complete responder had relapse-free survival up to 17 months. Major toxicities were cardiotoxicity and leukopenia. Eight patients were dead in the last follow-up; two of them died of treatment-related toxicity. The MFL regimen achieves little palliative benefit and induces severe toxicity at a fairly high rate. Administration of this regimen to breast cancer patients who have been treated by chemotherapy and those with impaired heart function requires careful attention.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Breast Neoplasms; Disease-Free Survival; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Leukopenia; Lung Neoplasms; Middle Aged; Mitoxantrone; Palliative Care; Prognosis; Survival Analysis

Nasopharyngeal carcinoma is a common cancer in South East Asia. In the early stages, radiotherapy alone may achieve sustained control, but once metastasis occurs, it becomes an incurable disease with limited survival time. We report a case of nasopharyngeal carcinoma, initial stage T4N0M0, diagnosed in 1985 in a patient aged 36 years who received 70 Gy radiotherapy to the head and neck region. In 1988, relapse occurred with multiple lung metastases. The patient received many chemotherapy regimens with a very good response, including near complete remission with the first treatment regimen of cisplatin, 5-fluorouracil and leucovorin for lung metastases, and with the fifth chemotherapy regimen of ifosfamide as a single agent. After ifosfamide treatment, there was residual fibrotic change in the lung and complete disappearance, lasting for almost a year, of the liver and bone lesions. The patient eventually died in July 1995 due to progressive disease. Prolonged survival after mainly thoracic metastasis is possible in patients with nasopharyngeal carcinoma, especially if the tumor is chemo-responsive.

Topics: Adult; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Fluorouracil; Humans; Ifosfamide; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Nasopharyngeal Neoplasms; Survivors

The prognosis of Stage III unresectable non-small cell lung cancer may be improved by concurrent chemoradiotherapy. In this study, we attempted to evaluate the feasibility, tolerance, efficacy and toxicities of the combination of thoracic radiation and chemotherapy with a novel regimen that included 5-fluorouracil, leucovorin, etoposide and cisplatin (the FLEP regimen) in the treatment of this group of patients.. From July 1995 to September 1996, 20 untreated patients with locally advanced non-small cell lung cancer were enrolled in the study. Radiation at a dose of 44 Gy was initially delivered in daily fractions of 2 Gy 5 days a week to the tumor and mediastinum, followed by a boost to the tumor (20 to 26 Gy according to patients tolerance). Concurrently with thoracic irradiation, patients were treated with chemotherapy consisting of cisplatin at the dose of 60 mg/m2/d for 1 day, etoposide at the dose of 60 mg/m2/d for 2 days, and 5-FU 500 mg/m2/d plus leucovorin 50 mg/d infusion for 48 hours. Cycles of chemotherapy were repeated every 3 weeks for a maximum of 3 cycles.. Seventeen of 20 patients were assessable. The overall response rate was 70.6% (95% confidence interval = 49-92%). No complete response was achieved. The median response duration for all responding patients is not yet estimable, with a range of 3.5 to 15.5+ months. Eleven patients remain progression-free for 4 to 15 months. The median survival for the entire group is not estimable. The major toxicity was esophagitis. Other grade 3 or 4 toxicities were not frequently observed.. Combined-modality therapy with FLEP regimen and radiation is a promising treatment with a high response rate and acceptable toxicity for locally advanced non-small cell lung cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Combined Modality Therapy; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Patient Compliance; Radiotherapy

Gestational trophoblastic disease (GTD) forms a heterogeneous pool of clinically and histopathologically defined entities with different malignant potential. The clinicopathologic characteristics of 158 cases, including 110 complete hydatidiform moles (CHM), 13 invasive moles, 32 choriocarcinomas, two placental site nodules and one placental site trophoblastic tumor are reported. Of all cases, 63.9% showed spontaneous regression after D&C. 36.1% resulted in a persistent or metastatic (11.4%) disease, including 12 CHM. Lung is found to be the most common site of metastasis (61%). The median time between antecedent pregnancy and GTD was 4.4 months. 44% had an antecedent CHM, 16% a term pregnancy. The median complete remission rate was 91.2% with 5.3% recurrent disease. Three women died. Eight patients received adjuvant surgical therapy for chemoresistant foci. In general, management of GTD is interdisciplinary with an emphasis placed on individualized treatment. In most cases, exact histopathologic diagnosis of the trophoblastic lesion remains the gold standard for guiding clinical therapy. Currently, there are no reliable genetic or molecular biologic markers predicting an aggressive behavior of CHM. Thus, all lesions should be followed by serial measurements of serum-HCG. All cases of persistent GTD should be treated in specialized centers.

Topics: Adolescent; Adult; Age Factors; Brain Neoplasms; Choriocarcinoma; Drug Therapy, Combination; Female; Humans; Hydatidiform Mole; Leucovorin; Lung Neoplasms; Methotrexate; Middle Aged; Pregnancy; Risk Factors; Tomography, X-Ray Computed; Treatment Outcome; Trophoblastic Neoplasms; Trophoblastic Tumor, Placental Site; Uterine Neoplasms

Three patients with lung metastases of renal cell carcinoma (RCC) were treated with a combination of interferon-alpha, leucovorin and 5-fluorouracil. All patients were male between 60 and 66 years and had been treated by nephrectomy prior to the combination therapy. Interferon-alpha was administered at the dose of 9 x 10(6) IU intramuscularly 3 times/week, leucovorin at 30 mg/m2 per day intravenously (day 1 to 5) and 5-fluorouracil at 500 mg/m2 daily by continuous infusion intravenously (day 1 to 5) followed by weekly bolus therapy. One patient achieved complete response for 17 months and the other two achieved stable disease for 6 and 16 months. Side effects related to this therapy were diarrhea, stomatitis, alopecia, leucocytopenia and thrombocytopenia. Grade 3 stomatitis occurred after the continuous administration of 5-fluorouracil in one patient; he recovered by discontinuation of 5-fluorouracil. Combination therapy with interferon-alpha, leucovolin and 5-fluorouracil might be effective for the treatment of lung metastases of RCC.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Renal Cell; Fluorouracil; Humans; Infusions, Intravenous; Interferon-alpha; Kidney Neoplasms; Leucovorin; Lung Neoplasms; Male; Middle Aged

A 33-year-old woman had undergone left mastectomy after diagnosis of breast cancer. One year after operation, multiple lung metastasis was confirmed by chest X-ray and CT scan. The patient received 6 courses of cyclophosphamide, epirubicin, and 5-FU (CAF) combined chemotherapy. However, the lesions were increased and the result of this chemotherapy was judged to be "progressive disease" (PD). A catheter was placed in the thoracic aorta, and FLEP combined intraaortic infusion chemotherapy was performed. The patient received 4 courses of 5-FU (325/mg/m2/day, civ, on day 1-5), leucovorin (30 mg/body/day, iv, on day 1-5), etoposide (60/mg/m2/day, ia, on day 7 and day 21), cisplatin (60/mg/m2/day, ia on day 7 and 21) every 4 weeks. The multiple lung metastasis almost disappeared on chest examination, and found to be less than 1 cm in diameter on CT scan. This result suggests FLEP combined chemotherapy is effective as a second-line treatment of recurrent breast cancer.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cisplatin; Drug Administration Schedule; Etoposide; Female; Fluorouracil; Humans; Infusion Pumps, Implantable; Leucovorin; Lung Neoplasms

The authors evaluated a high-intensity inpatient regimen using augmented but subtransplantation doses of multiple agents in patients with metastatic breast cancer. Two high-dose courses were given in an attempt to improve the efficacy of high-dose regimens using a single course.. Forty women received treatment between October 1988 and October 1991. The median age was 38 years (range, 24-56 years). Twenty-five patients were receiving their first chemotherapy for metastatic disease; 15 patients had received one or more prior regimens. The patients received two courses of chemotherapy, which consisted of the following: cyclophosphamide 1500 mg/m2 intravenously (i.v.) on days 1 and 2; doxorubicin 45 mg/m2 i.v. on days 1 and 2; cisplatin 20 mg/m2 i.v. on days 1, 2, 3, 8, 9, and 10; 5-fluorouracil 1000 mg/m2 on days 8, 9, and 10 (continuous infusion); methotrexate 100 mg/m2 i.v. on days 15 and 22; leucovorin 15 mg/m2 i.v. or by mouth for four doses beginning 24 hours after methotrexate. Etoposide 400 mg/m2 i.v. on days 1, 2, and 3 was substituted for doxorubicin in 14 patients who had received prior doxorubicin.. Twenty-nine of 40 patients (73%) had objective response to therapy, with 10 (25%) complete responses. Four patients who obtained a complete response remain disease-free at 14, 21, 28, and 32 months, respectively; all of these patients received this regimen as first-line therapy for metastatic disease. Myelosuppression was severe, with median durations of leukocytes less than 1000/microliters and platelets less than 50,000/microliters of 15 days (range, 7-48 days) and 13 days (range, 3-49 days), respectively. Moderate or severe mucositis occurred in 56 of 68 courses. Four patients (10%) had treatment-related deaths.. This regimen produced high overall response and complete response rates compared with standard regimens. However, only 15% of patients who received this therapy as first-line treatment for metastatic breast cancer remain disease-free, and median response duration was shorter than that reported using high-dose therapy with bone marrow support. Toxicity with this regimen was greater than anticipated, although myelosuppression and stomatitis would be reduced by the use of cytokines. This regimen does not improve results achieved with standard therapy sufficiently to justify its toxicity and expense.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Bone Neoplasms; Brain Neoplasms; Breast Neoplasms; Cisplatin; Cyclophosphamide; Doxorubicin; Etoposide; Female; Fluorouracil; Follow-Up Studies; Hemorrhage; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Methotrexate; Middle Aged; Neutropenia; Remission Induction; Survival Rate; Thrombocytopenia

From September 1989 to September 1992, 17 patients (pts) with non-curative or recurrent colorectal cancer were treated with 5-fluorouracil (FU) plus leucovorin (LV) systemic therapy. The sites of evaluable metastases were liver (10), peritoneum (4), lung (3) and others (6). The LV dosage was 30 mg/body (low-dose method) and the FU dosage was 500-750 mg/body. Both drugs were administered either 5 days/every 4 weeks or one day/every 1 to 2 weeks via protracted or bolus infusion. The regimen was generally well tolerated, although 9 pts (53%) experienced toxicity which required dose reductions. Overall response rate was 29% (5 PR). No CR was observed. Improvement in tumor-related symptoms was noted temporarily in 7 out of 10 pts. Serum CEA level decreased in 13 out of 14 pts. All the response sites were liver (5), with simultaneous lung (1) or peritoneum (1) metastasis. The response duration was 3 to 10 months (mean 6.2 months). Second-line therapy after progression of diseases, such as combination with CDDP, was attempted in some of the PR pts, but no re-response was observed. We conclude that FU plus low-dose LV regimen is an effective therapy for advanced colorectal cancer, but further attempts should be made to increase response rate, prolongation of response duration and effective second-line therapy after progression.

Topics: Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged

A 58-year-old woman with colon cancer, who had received oral 5-FU over 17 months after right hemicolectomy, was diagnosed as having a recurrence of the disease with multiple pulmonary metastasis. She was treated for 5 days with a combination of continuous infusion of 5-FU 600 mg/m2/day, bolus injection of leucovorin (LV) 20 mg/m2/day, and intramuscular injection of interferon (IFN)-alpha-2a (6.0 x 10(6) U/day, repeated every 3 weeks. The chest X-ray after three cycles showed a decrease in size of metastatic lesions by 51%, indicating a partial response. Correspondingly, the serum levels of CEA and CA 19-9 significantly decreased. There were modest but tolerable side effects such as fever, nausea, diarrhea, stomatitis, and alopecia. The patient has been given oral UFT and LV after discharge, and is still alive with continued improvement of pulmonary lesions even 9 months after initial chemotherapy. Although the detailed synergistic mechanism of 5-FU and IFN has yet to be determined, the addition of IFN, as a biochemical modulator distinct from LV, to the combination of 5-FU and LV, appears to further potentiate the therapeutic efficacy and may be useful for advanced colorectal cancer.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Female; Fluorouracil; Humans; Interferon alpha-2; Interferon-alpha; Leucovorin; Lung Neoplasms; Middle Aged; Recombinant Proteins

A 66-year-old man, who had received sigmoidectomy for sigmoid cancer in 1985, was diagnosed as having multiple lung and liver tumors in September 1988. When celiac-angiography was performed, recurrent liver metastases from sigmoid cancer were suspected and he received a transarterial embolism with ADM 30 mg and MMC 20 mg. In addition, he was treated with a sequential chemotherapy with methotrexate (MTX), 1,200 mg intravenously (6 h-infusion) followed by 5-fluorouracil (5-FU), 600 mg/m2/day and leucovorin, 300 mg/body/day in continuous infusion for 5 days from day 2 with concomitant oral administration of dipyridamole (300 mg/day) over 14 days. Treatment was repeated every 28 days for two courses. For the third course, administration of only 5-FU, leucovorin and dipyridamole was performed. As a result, the size of pulmonary lesions was prominently reduced on computed tomography. Although mucositis, anal erosion, diarrhea and thrombocytopenia were noted, no severe side effects were observed. This sequential chemotherapy appears useful for metastatic lesions from colon cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Lung Neoplasms; Male; Methotrexate; Neoplasm Recurrence, Local; Remission Induction; Sigmoid Neoplasms

A 72-year-old man underwent a radical operation for sigmoid colon cancer (well-differentiated adenocarcinoma, stage III) in 1989. Chest X-ray examination performed in September 1992 showed multiple nodular shadows in the lungs. A diagnosis of pulmonary metastasis was made from abnormally increased CEA and CA 19-9 and findings by chest tomography and CT scanning. There was no evidence of metastasis or recurrence in the liver, bone, brain or large intestine. He received three courses of bolus injections of leucovorin (30 mg/body) and 5-FU (500 mg/body), each over five consecutive days with a two-week rest period, and subsequently weekly at the same doses. CEA and CA 19-9 levels started to decrease after completion of the second course of consecutive treatment. In week 18 of chemotherapy, CEA and CA 19-9 levels dropped to 5.6 ng/ml and 32 U/ml from 66 ng/ml and 130 U/ml, respectively. Chest tomography and chest CT showed the disappearance or reduction in size of the nodules, with a reduction rate of 87.1%. Twenty-two weeks later, at this writing, there was no evidence of disease progression, and the patient was thus judged to be PR. He continues to receive chemotherapy at our outpatient clinic.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Fluorouracil; Humans; Injections; Leucovorin; Lung Neoplasms; Male; Postoperative Period; Sigmoid Neoplasms

Both cisplatin (CDDP) and leucovorin (LV) have been shown to enhance cytotoxicity of 5-fluorouracil (FUra) against murine and human neoplasms by increasing intracellular reduced folate concentrations. We were interested in their use in a combination to inhibit non-small cell lung cancer (NSCLC) cell growth and therefore conducted an in vitro study to investigate the cytotoxic activities of combinations of CDDP plus FUra, with and without LV (20 microM), against seven NSCLC cell lines. A tetrazolium assay with application of the classical isobole method was used to test drug combinations. We found that LV enhanced FUra but not CDDP cytotoxicity and that the degree of enhancement was negatively correlated with the effect of FUra. There was an overall additive combination effect of CDDP plus FUra, although there may be synergy at higher effect levels. There was synergy to a combination of CDDP, FUra, and LV, presumably primarily related to the synergistic effects of adding LV to FUra. In summary, LV and CDDP enhanced FUra cytotoxicity in a complementary fashion and there was clear synergy of a combination of CDDP, FUra, and LV against a panel of NSCLC cell lines. Our in vitro results provide a rationale for controlled clinical studies of this three-drug regimen in patients with NSCLC.

Topics: Carcinoma, Non-Small-Cell Lung; Cell Survival; Cisplatin; Drug Synergism; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Tumor Cells, Cultured

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Choriocarcinoma; Cyclophosphamide; Doxorubicin; Female; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Neoplasm Regression, Spontaneous; Vaginal Neoplasms

10-Ethyl-10-deazaaminopterin (EDX, edatrexate) exhibits therapeutic activity against methotrexate (MTX)-resistant tumors in animals and patients. In an effort to improve its efficacy among more chemoresistant tumors, studies were initiated in murine models of advanced metastatic disease comparing EDX and MTX at their maximum tolerated dose alone and in a high-dose regimen incorporating low-dose, delayed Ca leucovorin (LCV) rescue. Both twice-weekly x 3 and weekly x 3 schedules of administration were used with LCV given 16, 20, and 24 h after EDX. The LCV dose required to protect mice was 1/40 and 1/20 of the EDX or MTX dose, respectively, on either schedule. Therapy was initiated 5 or 6 days following i.v. implant of 5 x 10(5) cells of the E0771 mammary adenocarcinoma, T241 fibrosarcoma, Lewis lung carcinoma, B16 melanoma, or C38 colon carcinoma. MTX was essentially ineffective (increase in life span = < 30%) when given alone and either ineffective or only modestly effective (increase in life span = 20-80%) in increasing survival when given in the high-dose regimen to tumor-bearing mice. EDX alone was more effective than MTX when it was given in either regimen of therapy. Also, EDX given in the high-dose regimen (either twice-weekly or weekly x 3) was markedly more effective than EDX alone. Increased survival with this regimen was 2-3-fold greater than EDX alone against all 5 tumors, and long-term survivors were obtained with E0771 (20%), T241 (30-40%), Lewis lung (10-15%), B16 (20%), and C38 (40%) tumors. The administration of 6 doses rather than 3 doses on the twice-weekly schedule against T241 and Lewis lung tumors required a modest increase in the LCV dose but substantially improved efficacy, with as much as 70% long-term survivors (T241 tumor). We conclude that the use of a high-dose regimen with delayed LCV rescue markedly improved the therapeutic effectiveness of EDX against advanced metastatic disease in tumor-bearing mice. These studies should provide a framework for further clinical work with EDX, using this modality of therapy.

Topics: Adenocarcinoma; Aminopterin; Animals; Colonic Neoplasms; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fibrosarcoma; Leucovorin; Lung Neoplasms; Mammary Neoplasms, Experimental; Melanoma, Experimental; Methotrexate; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Neoplasm Metastasis; Neoplasm Transplantation; Neoplasms, Experimental; Salvage Therapy

A 62-year-old man diagnosed as Stage IIIB advanced non-resectable squamous cell carcinoma of the lung was treated with a sequential combination of 5-fluorouracil (5-FU) and cisplatin (CDDP), with concurrent administration of leucovorin and dipyridamole as a biochemical modulator for 5-FU. After 3 cycles, the mass reduced in size more than 70% in CT scan and the patient underwent a thoracotomy. Histologically, the primary lesion was completely necrotized and of the 10 metastatic regional lymph nodes, only one lymph node contained a small amount of viable cells and 3 additional cycles were conducted. The patient is still alive 30 months after initial chemotherapy. This regimen appears to be potentially useful for non-small-cell lung cancer and warrants further clinical study.

Topics: Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Dipyridamole; Drug Administration Schedule; Fluorouracil; Humans; Infusions, Intravenous; Injections, Intravenous; Leucovorin; Lung Neoplasms; Male; Middle Aged; Remission Induction

An intensive weekly chemotherapeutic treatment for extensive disease small-cell lung cancer was piloted in 14 patients. The regimen consisted of 6 drugs. Two drugs were given each week for a total of 12 weeks of treatment. Modifications were required in the protocol to attempt to overcome excessive toxicity. Unexpected toxicity included anemia requiring transfusions in 8 of 10 patients completing treatment, sepsis in 8 of 14 with 3 related deaths, and prolonged grade III motor neurotoxicity in 2 patients. All 3 patients who died of sepsis had shown evidence of response, and 8 of the remaining 11 had 90% or greater tumor shrinkage. Two others had a partial response. Median survival time for all patients was 9.3 months.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Cisplatin; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Etoposide; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Neoplasm Metastasis; Pilot Projects; Recurrence; Treatment Outcome; Vincristine

Leucovorin (LV) increases the cytotoxic effect of fluorouracil (FUra) and 5-fluoro-2'-deoxyuridine (FdUrd) by enhancing the formation of the fluorodeoxyuridine monophosphate (FdUMP) thymidylate synthase (TS) 5,10-methylenetetrahydrofolate (mTHF) ternary complex. To study the difference in the efficacy of this combination against different tumors, we compared the effect of LV (20 microM) on the cytotoxicity of FUra, FdUrd, and 5-fluorouridine (FUrd) in vitro against cell lines of five colorectal carcinomas (CC), five gastric carcinomas (GC), and four non-small-cell lung carcinomas (NSCLC) using the colony-forming assay. At the concentration used in the experiments, LV alone failed to inhibit colony formation in any of the cell lines tested. The NSCLC cell lines were more resistant to FdUrd than were the CC and GC lines. LV modulated the cytotoxicity of FdUrd in all five CC lines and in three of the five GC lines but failed to do so in any of the NSCLC lines. In addition, following 20 h treatment with 1 microM [3H]-FdUrd, formation of the FdUMP/TS/mTHF ternary complex was enhanced by LV in the LV-sensitized CC and GC cell lines but not in the LV-refractory NSCLC lines. These in vitro data corresponded well to the results of clinical trials. Therefore, the colony-forming assay may be useful for the identification of the sensitivity of tumors according to phenotype.

Topics: Adenocarcinoma; Carcinoma, Non-Small-Cell Lung; Cell Survival; Colony-Forming Units Assay; Colorectal Neoplasms; Drug Synergism; Floxuridine; Fluorodeoxyuridylate; Fluorouracil; Leucovorin; Lung Neoplasms; Stomach Neoplasms; Tetrahydrofolates; Thymidylate Synthase; Tumor Cells, Cultured

Topics: Adenocarcinoma; Diagnosis, Differential; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Porphyria Cutanea Tarda

Forty-one patients with metastatic colorectal cancer were treated every four weeks with methotrexate 25 mg/m2 i.v. days 1, 8, 15; vincristine 1 mg/m2 i.v. day 1; lomustine 100 mg/m2 p.o. day 1. Inclusion criteria were: failure of previous 5-fluorouracil/leucovorin treatment; performance status (ECOG) 0-2; age less than 60 years; presence of symptoms; absence of concomitant diseases. Metastatic sites were: liver 30, lung 4, abdominal/pelvic mass 7. Three patients achieved partial responses (2 liver, 1 lung metastases); 4 showed stable disease and 34 progressed on therapy. The median survival of patients with partial response, stable disease and progression was comparable (24, 21, 22 weeks respectively). The most common toxicity was hematologic (thrombocytopenia and leukopenia). Other side effects included nausea and vomiting, stomatitis and diarrhea. Symptoms were not affected by treatment. We conclude that salvage chemotherapy is not recommended in colorectal cancer after 5-fluorouracil/leucovorin treatment even in patients with generally considered favorable characteristics for response to chemotherapy.

Topics: Adenocarcinoma; Adult; Age Factors; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Lomustine; Lung Neoplasms; Male; Methotrexate; Middle Aged; Salvage Therapy; Survival Rate; Vincristine

The present study was designed to analyse the cytotoxic effects of the combination of fotemustine plus 5-fluorouracil (5-FU) and folinic acid (FA). Two human tumor cell lines were used; one line was derived from colon cancer (WIDR) and the other from a non-small cell lung cancer (CAL 12). Cytotoxic effects were assessed by the MTT semi-automated test in 96-well incubation plates. The effects of various drug combinations were evaluated by the isobologram method. The drug combinations tested included fotemustine concentrations of 20, 30, 40, 50 and 70 micrograms/ml, 5-FU concentrations of 5, 15 and 30 micrograms/ml, and a constant FA concentration of 10(-5) M. A total of 180 different experimental conditions were tested. When cells were exposed to fotemustine before 5-FU the final cytotoxic effects for both cell lines were additive or synergistic in the majority of cases (P less than 0.001). The 5-FU concentration was a determinant factor affecting modification of the effects of the drug combination from antagonism (with low 5-FU concentrations) to synergism (high 5-FU concentrations) (P less than 0.001). Addition of FA (10(-5) M) resulted in a significant shift towards synergistic associations for both cell lines. Administration of 5-FU before fotemustine caused a marked antagonism which 10(-5) M FA was unable to significantly shift towards simple additivity.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cell Survival; Colorectal Neoplasms; Dose-Response Relationship, Drug; Drug Antagonism; Drug Synergism; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Nitrosourea Compounds; Organophosphorus Compounds; Tumor Cells, Cultured

The case of an extensive pulmonary artery sarcoma managed by radical excision and homograft reconstruction followed by aggressive chemotherapy and irradiation with prolonged survival is presented. Pulmonary artery sarcomas are reviewed with emphasis on the diagnosis and management of these usually fatal tumors.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cardiopulmonary Bypass; Doxorubicin; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Middle Aged; Pulmonary Artery; Sarcoma; Vascular Diseases

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Dipyridamole; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Lung Neoplasms; Male; Middle Aged; Pilot Projects

Edatrexate (10-ethyl-10-deaza-aminopterin; CGP 30 694) is a methotrexate (MTX) analogue that shows promise against non-small-cell lung cancer (NSCLC) and other tumors. Since edatrexate's mechanism of action is the same as that of MTX, we used leucovorin in an attempt to alleviate its dose-limiting toxicity, stomatitis. In four patients with NSCLC who had experienced significant stomatitis after treatment with edatrexate, cyclophosphamide, and cisplatin, we observed a remarkable reduction in stomatitis following the administration of low-dose leucovorin. On the basis of the results obtained in these individuals, we treated 15 additional patients with this three-drug regimen plus leucovorin rescue. These subjects could tolerate the treatment with lesser degrees of stomatitis and received higher edatrexate doses in subsequent courses as compared with the patients who previously received this regimen without leucovorin rescue. This approach is expected to improve the therapeutic indices of edatrexate and edatrexate-containing chemotherapy regimens by modifying the dose-limiting toxicity of this antineoplastic agent.

Topics: Aminopterin; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Cyclophosphamide; Dose-Response Relationship, Drug; Drug Evaluation; Drug Tolerance; Female; Folic Acid Antagonists; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Stomatitis

The present study was designed to analyse the cytotoxic effects of the combination of fotemustine with 5-fluorouracil (5-FU) plus folinic acid (FA). Two human tumor cell lines were used; one line was derived from colon cancer (WIDR) and the other, from a non-small-cell lung cancer (CAL 12). Cytotoxic effects were assessed using the MTT (tetrazolium bromide) semi-automated test in 96-well incubation plates. The effects of various drug combinations were evaluated by the isobologram method. The drug combinations tested included fotemustine concentrations of 20, 30, 40, 50 and 70 micrograms/ml, 5-FU concentrations of 5, 15 and 30 micrograms/ml, and a constant FA concentration of 10(-5) M. A total of 180 different experimental conditions were tested. When cells were exposed to fotemustine prior to treatment with 5-FU, the final cytotoxic effects on both cell lines were additive or synergistic in the majority of cases (P less than 0.001). The 5-FU concentration was a determinant factor that modified the effects of the drug combination from antagonism (at low 5-FU concentrations) to synergism (high 5-FU concentrations; P less than 0.001). The addition of FA (10(-5) M) resulted in a significant shift towards synergistic associations in both cell lines. Administration of 5-FU prior to treatment with fotemustine caused marked antagonism, which 10(-5) M FA could not significantly shift towards simple additivity.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cell Line; Cell Survival; Colonic Neoplasms; Dose-Response Relationship, Drug; Drug Interactions; Drug Screening Assays, Antitumor; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Nitrosourea Compounds; Organophosphorus Compounds; Tumor Cells, Cultured

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Mouth Mucosa; Stomatitis; Vinblastine; Vinorelbine

Twenty-three patients with regionally advanced non-small cell lung cancer (NSCLC) (Stage III) were treated with continuous infusion 5-fluorouracil (5-FU) augmented by high-dose oral leucovorin and hydroxyurea and concomitant radiotherapy. This chemoradiotherapy regimen was administered during 5 days of every other week for six cycles (total radiation dose, 6000 cGy). Three patients (13%) had stable disease, 13 patients (57%) had a partial response (PR), and 1 patient (4%) had a complete response (CR). The overall response rate was 61% (95% confidence interval, 41% to 81%). At a median follow-up time of 19 months, the median survival time for all 23 patients was 12 months. The median time to disease progression was 6 months. Twelve patients have had disease progression outside of the chest, and only 3 patients have had intrathoracic disease progression as the site of first failure. The toxicities of this regimen consisted of mild to moderate myelosuppression and moderate degree dermatitis and mucositis. It was concluded that concomitant chemoradiotherapy with this regimen results in high local activity at acceptable toxicity. However, the systemic activity of this regimen was low, resulting in a high distant recurrence rate and a median survival time that was not different from that achieved with standard therapy. Therefore, its use, as defined in this study, cannot be recommended.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Combined Modality Therapy; Drug Administration Schedule; Drug Evaluation; Female; Fluorouracil; Follow-Up Studies; Humans; Hydroxyurea; Leucovorin; Lung Neoplasms; Male; Middle Aged; Pilot Projects; Radiotherapy Dosage

Reduced folates have been shown to increase the cytotoxicity of 5-fluorouracil (FUra) by stabilizing the fluorodeoxyuridine monophosphate:thymidylate synthase complex, thus increasing the block in the DNA synthetic pathway. Using an in vitro tetrazolium colorimetric (MTT) cytotoxic assay, we tested the effects of FUra and 5-fluorodeoxyuridine (FUdR) with and without leucovorin (LV) on a panel of 7 human lung cancer cell lines. LV at a concentration of 20 microM enhanced the cytotoxicity of FUra and of FUdR in all of the cell lines. Quantitatively, LV had a higher degree of enhancement on FUdR than on FUra cytotoxicity in 6 cell lines. There was equivalent enhancement in the only remaining line. The differential effects of LV on the cytotoxicity of FUra vs. FUdR in these lung carcinoma lines contrasts with a quantitatively similar enhancement of cytotoxicity between FUra and FUdR in colon cancer lines previously reported from our laboratory. This suggests that the metabolism of FUra may be different in these lung cancer cell lines.

Topics: Adenocarcinoma; Adenocarcinoma, Bronchiolo-Alveolar; Carcinoma, Squamous Cell; Cell Line; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Drug Synergism; Floxuridine; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Tumor Cells, Cultured

Fourteen patients with inoperable or recurrent non-small cell lung cancer (NSCLC) were treated with 5-fluorouracil (5-FU) plus high-dose leucovorin (LV). The administration schedule was 2 h infusion of LV at a dose of 500 mg/m2 and 30 min infusion of 5-FU at a dose of 600 mg/m2 given 1 h after the start of the LV infusion. This regimen was followed weekly, six times. No objective (complete or partial) response was seen in any of the patients. Ten patients showed no change and there were four with progressive disease. One patient experienced grade 3 leukopenia after two courses of treatment. Another experienced grade 2 leukopenia. One patient experienced grade 2 vomiting and six, skin pigmentation. Other myelosuppressive effects and non-hematologic toxicities, including diarrhea and mucositis, were mild. It was concluded that the schedule of 5-FU with high-dose LV therapy employed could not be expected to produce a response rate greater than or equal to 20% against NSCLC. 5-FU plus high-dose LV therapy was, therefore, considered to be ineffective against NSCLC with the schedule of administration followed.

Topics: Adult; Aged; Carcinoma, Non-Small-Cell Lung; Drug Evaluation; Female; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged

A 60-year-old female presented with a one-year history of multiple enlarging tender subcutaneous nodules. Initial biopsy demonstrated a poorly differentiated adenocarcinoma. Mammography showed multiple nodular breast lesions. After the patient failed to respond to tamoxifen, a second biopsy demonstrated a metastatic carcinoid tumor. Further search revealed a single small pulmonary nodule, which on aspiration biopsy proved to be a carcinoid tumor. The patient failed to respond to treatment with streptozotocin and 5'-fluorouracil. Therapy with leucovorin calcium and 5'-fluorouracil then produced a partial response.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoid Tumor; Female; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Middle Aged; Skin Neoplasms

The interim results of the use of high-dose methotrexate with leucovorin rescue for the treatment of 26 patients with osteogenic sarcoma are discussed. Preoperative chemotherapy was followed by marked regression of primary tumor in one out of seven patients with localized disease. In that group, metastasis-free period lasted 2, 3, 10+, 12, 17+ and 24+ months. Response was observed in two out of 19 (10.6%) cases of metastases. Toxic side-effects were moderate and were mainly nausea (38.5% of patients), vomiting (26.9%), elevation of serum transaminase levels (38.5%) and fever (30.7% of cases).

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Child; Drug Evaluation; Female; Femoral Neoplasms; Humans; Humerus; Leucovorin; Lung Neoplasms; Male; Methotrexate; Osteosarcoma; Preoperative Care; Tibia

Lymphomatoid granulomatosis is an uncommon disorder with features of vasculitis and lymphoma. Treatment has usually consisted of steroids and, occasionally, single cytotoxic drugs, but prognosis remains poor. The authors report a patient with life-threatening disease treated successfully with combination chemotherapy consisting of methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) who achieved complete remission and remains disease-free over 3 years from diagnosis. Justification for an aggressive therapeutic approach to this disease is presented.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Female; Humans; Leucovorin; Lung Neoplasms; Lymphomatoid Granulomatosis; Methotrexate; Middle Aged; Neoplasms, Multiple Primary; Prednisone; Remission Induction; Skin Neoplasms; Vincristine

We have carried out a phase II study evaluating the activity of a 5-fluorouracil drug combination in patients with advanced non-small-cell lung cancer. Patients were given 60 mg/m2 of methotrexate i.v. on day 1. On day 2, 750 mg/m2 of 5-fluorouracil was administered as a 24-h infusion daily for 3 days. Also on day 3, 10 mg/m2 of mitomycin was given i.v. along with folinic acid. Folinic acid was started on day 3 initially at a dose of 25 mg/m2 intravenously every 6 h for three doses, followed by a 2-h infusion of 200 mg/m2 daily on days 3 and 4. Therapy was repeated every 28 days. Fourteen of 35 patients (40%) experienced a partial response to chemotherapy. The median survival of the entire group was 19 weeks. Mucositis was a common side effect but severe leukopenia, anemia, renal insufficiency, and skin ulceration were rare. This study demonstrated that 5-fluorouracil infusion therapy has activity in advanced non-small-cell lung cancer but the responses are not durable. Further studies evaluating differing dose schedules and alternate 5-fluorouracil infusion-based drug combinations seems warranted.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Drug Evaluation; Female; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Methotrexate; Middle Aged; Mitomycins; Neoplasm Staging

Eighty-two patients with small cell lung cancer (SCLC), 32 with limited disease, were treated with alternating chemotherapy. Eight courses were administered at weekly intervals, and responding patients received radiotherapy to sites of bulk disease. Overall response rate was 76.8%. Overall median survival was 265 days, 408 days in patients with limited disease. The median symptom free period after chemotherapy was completed was 123 days. These results are comparable with those in reports of chemotherapy of longer duration and warrant the further investigation of short duration treatment in this disease.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Etoposide; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Middle Aged; Time Factors; Vincristine

A report is presented on 5 cases of pneumothorax which occurred during chemotherapy in patients suffering from osteogenic sarcoma of the extremities. None of them presented radiographically detectable substitutive pulmonary lesions. It was hypothesised that the origin of pneumothorax was the necrosis produced by agents of a pulmonary micrometastasis.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Doxorubicin; Extremities; Female; Humans; Leucovorin; Lung Neoplasms; Male; Methotrexate; Osteosarcoma; Pneumothorax; Time Factors; Vincristine

27 patients with advanced colorectal cancer were treated in a phase-II trial with high dose sequential methotrexate (MTX), 5-fluorouracil (5-FU), and folinic acid (FA). Following a 4 h infusion of 800 mg/m2 MTX and a 4 h interval, 1,500 mg/m2 5-FU and 200 mg/m2 FA were given as a 24 h infusion. Out of 23 evaluable patients we observed one partial remission and 9 disease stabilizations. Median survival time of all patients was 10.4 months. Overall toxicity was low. In comparison to a previous trial we did not observe better treatment results by adding high dose FA to a sequential MTX/5-FU schedule.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Methotrexate; Middle Aged; Remission Induction

A case of pulmonary T-cell lymphoma in an Acquired Immune Deficiency Syndrome (AIDS) patient is presented. Morphologically, it belonged to the large cell, immunoblastic category of the Working Formulation and demonstrated a helper/inducer phenotype. Clinically there was no association with manifestations of human T-lymphotropic virus (HTLV)-I related lymphoma and the patient was seronegative for HTLV-I and HTLV-II antibodies. High-grade B-cell lymphomas occur with an increased frequency in patients with AIDS but the occurrence of a peripheral T-cell lymphoma in AIDS has not been documented before. The case is discussed in the context of current concepts of AIDS-related lymphomagenesis.

Topics: Acquired Immunodeficiency Syndrome; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dexamethasone; Doxorubicin; HIV; Humans; Immunohistochemistry; Leucovorin; Lung Neoplasms; Lymphoma; Male; Methotrexate; T-Lymphocytes; Vincristine

From 1977 to 1982, 62 patients with various advanced malignant solid tumors were treated by HD-MTX-CFR therapy and totally 129 courses were given. Majority of the patients suffered from malignant lymphoma (10), osteogenic sarcoma (11), lung cancer (16), esophageal cancer (3), breast cancer (3) and malignant melanoma (4). All were confirmed by cytology or pathology except one primary liver cancer. There were clinically measurable lesions in 59 patients for evaluation of the treatment, and 3 osteogenic sarcoma patients without metastasis were given a postoperative adjuvant chemotherapy. 33 out of 62 had received chemotherapy and/or radiotherapy before. Dose of MTX ranged from 2 to 3 gm per course in most patients and dose of CF, from 9 to 12 mg every 6 hours for 3 days. 2 (3.4%) patients achieved complete remission (1 osteogenic sarcoma and 1 malignant lymphoma) and 8 (13.6%), partial remission (1 osteogenic sarcoma, 5 malignant lymphoma, 1 esophageal cancer and 1 breast cancer) with a total response rate of 15.9%. No response was observed in all 16 lung cancers. The main side effects of HD-MTX-CFR therapy were leukopenia, thrombocytopenia, elevation of SGPT, nausea, vomiting, mucositis, skin rash, fever and fatigue. All patients were followed more than 3 years. 4 patients are still alive (9, 9, 4 and 7 years, respectively), including 3 osteogenic sarcoma patients who received postoperative adjuvant chemotherapy and 1 mycosis fungoides.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Follow-Up Studies; Humans; Leucovorin; Lung Neoplasms; Lymphoma; Male; Methotrexate; Middle Aged; Neoplasms; Osteosarcoma

Topics: Administration, Oral; Animals; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Drug Administration Schedule; Fluorouracil; Half-Life; Humans; Infusions, Intravenous; Leucovorin; Leukemia, Experimental; Lung Neoplasms; Mice; Mice, Inbred DBA; Neoplasms, Experimental

Twenty patients with osteosarcoma and pathologic fractures were treated with a chemotherapeutic regimen consisting of cis-diamminedichloroplatinum-II (CDP), Adriamycin (ADR) (doxorubicin) and high-dose methotrexate with citrovorum factor "rescue" (MTX-CF). Before the introduction of the regimen, the primary tumor in two patients was treated by immediate amputation and in 13 with preoperative intra-arterial CDP. Among these 13 patients, responses (healing) were observed in 11 (one required the addition of radiation therapy). In three patients, the responses were so dramatic that, at their request, surgery was deferred and treatment exclusively with chemotherapy was instituted. Based on this experience, treatment exclusively with chemotherapy was also administered to an additional five patients who were admitted without pathologic fractures. In the course of such treatment, pathologic fractures also developed; notwithstanding, chemotherapy was maintained and healing also occurred. One of the 20 patients had pulmonary metastases at diagnosis; these were resected after treatment and pathologic examination revealed no evidence of viable tumor. The remaining 19 patients were free of pulmonary metastases but these later developed in seven patients. These data were compared to a historical control series in which 16 of 21 patients with pathologic fractures developed pulmonary metastases. Three of the chemotherapy treated patients died of nonosteosarcoma related causes (leukemia, generalized varicella, and a metabolic complication). Overall, survival was improved in the chemotherapy treated patients as compared to the historical control series: 10 of 20 versus 6 of 21, respectively. Pathologic fractures in osteosarcoma may heal under treatment with chemotherapy, which also has a favorable impact on the eradication of pulmonary metastases and survival.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cisplatin; Doxorubicin; Fractures, Spontaneous; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Osteosarcoma

The primary site of the metastasis of osteosarcoma is the lung. More than 90% of patients have died of pulmonary metastasis in one to two years. Control of osteosarcoma depend upon the prevention of its pulmonary metastasis. The introduction of chemotherapy consisting mainly of Adriamycin, high-dose methotrexate with Leucovorin rescue and Cisplatinum, dramatically improved the prognosis of osteosarcoma. In the past, when systemic chemotherapy was not available, the five-year survival rate was around 19%. In patients who receive chemotherapy with the current combination of chemotherapeutic agents (ADM, HD-MTX, VCR, CPM, CDDP), the incidence of pulmonary metastasis was low, and the five-year survival rate increased to 65%. In patients who receive chemotherapy, pulmonary metastasis may be either delayed, with a single metastasis appearing after termination of treatment (late isolated type), or early and multiple, emerging in reaction to treatment (early multiple type). It is generally accepted that post-operative chemotherapy can inhibit pulmonary micro metastasis and prove to be of great significance in improving the survival rate of patients with osteosarcoma of extremities and achieve limb salvage operation. On the other hand, effective control of the side effects of drug administration such as nausea, vomiting, alopecia, cardio (ADM) and renal (CDDP) toxicity and bone marrow suppression, is a problem that must be solved as soon as possible.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cisplatin; Doxorubicin; Humans; Leucovorin; Lung Neoplasms; Male; Methotrexate; Osteosarcoma; Postoperative Care

Thirty-nine women with nonmetastatic gestational trophoblastic disease as determined by conventional staging studies were prospectively evaluated with computed axial tomography (CAT) of the lungs. Sixteen patients (41%) had pulmonary micrometastases detected by CAT, which were not detected by routine chest x-ray. Eight patients (20.5%) had indeterminate scans, and only 15 patients (38%) had negative scans. Eight of 16 patients (50%) with pulmonary micrometastases failed initial therapy with methotrexate-folinic acid rescue while one of eight (12.5%) patients in the indeterminate group and one of 15 (6.7%) patients in the true nonmetastatic group failed initial therapy (P less than .006). All patients who failed methotrexate-folinic acid rescue ultimately achieved prolonged remission with actinomycin D. Time to remission was significantly decreased in patients without evidence of pulmonary micrometastases (P = .03), but the total number of courses of chemotherapy was not significantly different (P = .06). No life-threatening toxicity occurred. Pulmonary micrometastases detected by CAT but not chest x-ray are predictive of an increased risk of methotrexate-folinic acid therapy failure. Computed axial tomography of the lungs identifies a group of patients at high risk for failure of methotrexate-folinic acid rescue, and, therefore, may be indicated for routine staging of patients with otherwise nonmetastatic gestational trophoblastic disease.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Chorionic Gonadotropin; Female; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Middle Aged; Neoplasm Staging; Pregnancy; Tomography, X-Ray Computed; Trophoblastic Neoplasms; Uterine Neoplasms

The case of an 11-year-old girl suffering from chondroblastic osteosarcoma of the left tibia head is reported. Within 19 months following the amputation of the thigh and during intensive chemotherapy a total of 7 pulmonary metastases were diagnosed and resected in 3 sessions. The patient has been free of any metastases for 5 years.

Topics: Amputation, Surgical; Bleomycin; Child; Chondroblastoma; Cyclophosphamide; Dactinomycin; Female; Humans; Ifosfamide; Leucovorin; Lung Neoplasms; Methotrexate; Osteosarcoma; Tibia

The study of stem cell defects in man after cytoreductive therapy appears to be of particular importance since hematotoxicity represents the major limiting side effect in many instances. On the other hand, such studies are met by difficult methodological problems. In particular, bone marrow sampling in man cannot be done on a quantitative basis. Furthermore, ethical considerations restrict the sampling of serial bone marrow specimens. We have studied the reaction of hematopoiesis including stem cells in man with the available methods, in particular CFU-GM (CFU-C), CFU-E, and BFU-E in bone marrow (BM) and peripheral blood (PB) during the course of various cytostatic regimens given for adjuvant and palliative chemotherapy of human cancer. Major findings of these studies were The acute reaction of BM stem cells and differentiated BM precursor pools corresponds to the mechanisms known to be effective in animal experiments. The PB CFU-GM may be of particular importance in man in demonstrating long-term derangements. In an attempt at quantification of human BM data, an index was developed from BM spicule morphometry and from standardized BM aspirate cellularity. Stem cell defects in BM and PB were observed that did not show up in the PB counts, in particular after nitrosoureas. Indication of prolonged derangements in stem cells up to five years after chemotherapy were observed after adjuvant therapy for breast cancer. From these data, it appears advisable to study stem cell data in man for newly developed chemotherapeutic regimens in order to minimize early and late side effects on hematopoiesis.

Topics: Animals; Antineoplastic Agents; Blood Cells; Bone Marrow; Breast Neoplasms; Carcinoma, Small Cell; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Fluorouracil; Gastrointestinal Neoplasms; Hematopoietic Stem Cells; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Nitrosourea Compounds; Regeneration; Reticulocytes; Vincristine

Most cancerocidal agents have myelosuppression as their major toxicity. In some clinical studies it has been possible to show a relationship between the amount of administered drug and the therapeutic efficacy. Within any defined protocol, however, there may be much variability in the severity of myelosuppression. We attempted to determine whether the tumor response might be related to this toxicity. We evaluated a total of 177 patients with small cell bronchogenic carcinoma, treated by five successive regimens of combination chemotherapy, consisting of either cyclophosphamide and vincristine alone or with doxorubicin or doxorubicin plus bacillus Calmette-Guerin (BCG) or doxorubicin plus methotrexate, for a number of prognostic factors (age, sex, extent of disease, performance status, sites and number of metastases, serum LDH and alkaline phosphatase, weight loss, leukopenia, and thrombopenia). Leukopenia (mean 415 +/- 478/mm3, range 0-2000/mm3) had a weak influence on the incidence of complete remission, which was highest with the least severe nadir (P = 0.027). Thrombopenia was a nonsignificant factor (P = 0.738). Both leukopenia and thrombocytopenia had no influence on the overall survival. Because these drug combinations were based on cyclophosphamide, which requires metabolic activation, we evaluated the relationship of myelosuppression and the incidence of response in a second group of patients with small cell bronchogenic carcinoma treated with a VP16, cyclophosphamide, doxorubicin, vincristine sulfate protocol. In this analysis, no relationship could be detected between remission and myelosuppression. Granulocytopenia or thrombocytopenia also-showed no significant influence on the achievement of long-term survival beyond 36 months.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Bronchogenic; Carcinoma, Small Cell; Cyclophosphamide; Dactinomycin; Doxorubicin; Etoposide; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Vincristine

Between January 1975 and December 1981, 160 patients with metastatic non-oat cell bronchogenic carcinoma (MNOBC) were treated with cyclophosphamide, doxorubicin, methotrexate, and procarbazine (CAMP), or with a CAMP-like regimen. Forty-two (26%) of these patients demonstrated an objective response to the chemotherapy with a median survival of 61 weeks. Thirty-nine (24%) patients had stable disease (SD) with a median survival of 45 weeks. Seventy-nine patients (49.4%) were nonresponders with a median survival of 15 weeks. There was a significant difference in survival times between the responders and the SD patients, and between the responders and SD patients and the nonresponders. Responses were seen in 11% of the patients with squamous cell carcinoma and in 37% of the patients with adenocarcinoma. There was a significant difference in the response and SD categories in favor of adenocarcinoma over squamous cell carcinoma. Once a response was achieved, the median survival of the patients with adenocarcinoma was not significantly longer than that of the patients with squamous cell carcinoma.

Topics: Actuarial Analysis; Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Bronchogenic; Carcinoma, Squamous Cell; Cyclophosphamide; Doxorubicin; Female; Humans; Leucovorin; Lung Neoplasms; Male; Methotrexate; Middle Aged; Neoplasm Metastasis; Procarbazine

A new concept of chemotherapy scheduling was evaluated in 20 patients with inoperable squamous cell lung cancer. The complete plus partial response rate was 85%, with 15% complete responses. The drugs utilized included vinblastine, bleomycin, methotrexate, 5-FU, cisplatin, and leucovorin. The hypothesis leading to the chosen drug schedule was that impaired rbc deformability (RBCD) found in cancer patients may produce stasis of flow in tumor capillary beds and decrease drug delivery to cancer cells. Drug schedules were designed to take advantage of chemotherapy-induced improvement in RBCD. After an initial drug treatment, a second treatment was given when RBCD increased at least 25% over pretreatment values (usually 4-6 days after the first chemotherapy dose). Drug doses were weighted so that more drug was given when RBCD was greatest. Treatment toxicity was predominantly hematopoietic and renal. This type of chemotherapy approach opens up new avenues of investigation in squamous cell cancer and other common neoplasms.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Erythrocytes; Fluorouracil; Hematopoiesis; Humans; Kidney; Leucovorin; Lung Neoplasms; Male; Methotrexate; Middle Aged; Vinblastine

Five murine tumor cells (sarcoma 1509a, Gc-4, YAC-1, Dunn osteosarcoma, Lewis lung carcinoma) were exposed to methotrexate (MTX) at concentrations of 10(-1)-10(-9) mg/ml for 4-72 hours in vitro and then assayed for their viability. The effect of cell killing by MTX was dependent on both exposure time and concentration of the agent. MTX at a concentration of 10(-5) mg/ml killed the entire cell population in 72 hours, whereas the agent was not particularly effective even at a concentration of 10(-1) mg/ml on exposure for 4 hours. There was a close relation between doubling time of tumor cells and exposure time to MTX for killing entire populations of the tumor cells. The longer doubling time of the tumor cells was, the longer exposure time to MTX was needed to kill them. Lewis lung carcinoma was less sensitive to MTX than other sarcomas. The effect of citovorum factor (CF) on tumor cell killing by MTX was studied on sarcoma 1509a. After exposure to MTX sarcoma 1509a populations could not be rescued by the treatment of CF.

Topics: Animals; Cell Division; Cells, Cultured; Drug Evaluation, Preclinical; Leucovorin; Lung Neoplasms; Methotrexate; Mice; Neoplasms, Experimental; Osteosarcoma; Sarcoma, Experimental; Time Factors

Twenty-six evaluable patients with advanced soft tissue and bony sarcomas refractory to chemotherapy were treated with vincristine plus high-dose methotrexate and leucovorin rescue. A 14% response rate was observed among 14 patients presenting with refractory soft tissue sarcomas. No responses were observed among 12 patients with bony sarcoma. Toxic reaction with nausea, vomiting, nephrotoxicity, and myelosuppression was manageable. While this study did demonstrate activity of this regimen in doxorubicin-refractory patients, the duration of the responses was relatively brief. Thus, the clinical utility of such a regimen is questionable.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Dose-Response Relationship, Drug; Drug Evaluation; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Sarcoma; Vincristine

Few studies have incorporated high-dose methotrexate (MTX) with leucovorin rescue in the treatment of small cell lung cancer (SCLC). Potentially therapeutic levels of MTX can be achieved in the central nervous system (CNS) by systemic administration of high doses of this drug. Utilizing a combination chemotherapy program of Adriamycin, vincristine, cyclophosphamide, and methotrexate, 31 patients were sequentially assigned to receive either low-dose MTX (40 mg/m2), or high-dose MTX (500 mg/m2) with leucovorin rescue. Radiation therapy to the primary site was also administered. At these dosage levels there were no statistically significant differences in response rate or survival between the two groups. High-dose MTX did not prevent the appearance of CNS disease; there being 2/15 and 3/15 CNS relapses in the HD MTX and LD MTX treated groups, respectively. The occurrence of CNS disease did not significantly affect overall survival as compared to patients not similarly affected.

Topics: Aged; Carcinoma, Small Cell; Drug Therapy, Combination; Female; Humans; Leucovorin; Leukopenia; Lung Neoplasms; Male; Methotrexate; Middle Aged; Neoplasm Recurrence, Local; Nervous System Neoplasms; Paraneoplastic Syndromes; Smoking; Thrombocytopenia

Since October 1973, 185 patients 21 years of age or younger with primary osteogenic sarcoma of an extremity were treated with adjuvant chemotherapy. Twenty-five of the first fifty-two patients (48%) have remained free of disease for a median of 7 years. In the next chemotherapy protocol most patients had chemotherapy prior to amputation or resection, during which time the dose of high-dose methotrexate was escalated in many patients to that needed to shrink the primary tumor. For a median of 4 years 43 of 54 patients (80%) have remained free of disease. In the current protocol, the response of the primary tumor to chemotherapy with high-dose methotrexate was used to select postoperative adjuvant chemotherapy for the patient. With the latter approach 73 of 79 patients (92%) have remained continuously free of disease for a median of 2 years. This experience demonstrates the value of chemotherapy in increasing the cure rate in osteogenic sarcoma and that the response to preoperative chemotherapy can help select postoperative chemotherapy to produce an even higher potential cure rate for osteogenic sarcoma.

Topics: Adolescent; Adult; Antineoplastic Agents; Bone Neoplasms; Drug Therapy, Combination; Female; Humans; Leucovorin; Lung Neoplasms; Male; Methotrexate; Osteosarcoma; Preoperative Care; Radiography; Time Factors

Thirty-one patients with unresectable non-small cell carcinoma of the lung (19 adenocarcinoma, 7 large cell carcinoma, 4 squamous cell carcinoma, 1 mixed histology) were treated with one of two intravenous infusion schedules of high dose methotrexate with leucovorin rescue. First, 14 patients received methotrexate in escalating doses from 1.5 to 12 g/m2 over 6 hours followed immediately with leucovorin 15 mg/m2 for 12 doses every 6 hours; there were no complete or partial responses among these 14 patients. Then, 17 patients were treated with a loading bolus of 50 mg/m2 intravenous methotrexate followed by a 30-hour continuous infusion of 1.5 g/m2. Leucovorin 15 mg/m2 every 6 hours for 12 doses was begun at the end of the infusion. There were 3 partial responses among the 17 patients in this group. The results demonstrate that both 6- and 30-hour infusions of high-dose methotrexate regimens can be given safely to middle aged adult patients, but the overall 10% response rate does not appear to be significantly different than the results with standard-dose methotrexate.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Aspartate Aminotransferases; Creatinine; Drug Administration Schedule; Female; Hematologic Diseases; Humans; Leucovorin; Lung Neoplasms; Male; Methotrexate; Middle Aged

Twenty-five patients with non-small cell lung cancer (NSCLC) were treated with high-dose methotrexate with citrovorum factor resuce (HDMTX-CFR), mechlorethamine (HN2) and procarbazine (PCZ). Nineteen patients are evaluable for response. One patient had partial remission which lasted for 11 weeks. Nine patients had stable disease lasting for 6-22 weeks. HDMTX-CFR was well tolerated by these patients but this combination regimen produced very low tumor response rate (5.2%). Addition of HN2 and PCZ, chemotherapeutic agents active against NSCLC, failed to improve the tumor response rate but added to gastrointestinal and hematologic toxicity.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Leucovorin; Lung Neoplasms; Male; Mechlorethamine; Methotrexate; Middle Aged; Procarbazine

Ninety-eight patients with small cell carcinoma of the bronchus (SCCB) were treated with a combination of cyclophosphamide, methotrexate with calcium leucovorin rescue, and lomustine (CCNU). VP-16-213 was given on relapse. Response rate and survival were analyzed according to extent of tumor, presence of the syndrome of inappropriate antidiuretic hormone production (SIADH), and, in 38 patients, size of intrathoracic tumor as measured by computerized tomographic (CT) scanning. The median survival of the entire group was 34.6 weeks. In patients with limited disease the median survival was 46 weeks compared to 29 weeks for those with extensive disease. This difference in survival between patients with limited and extensive disease was most marked in those showing a partial response (median survival, 45.9 and 28 weeks, respectively). Patients with ectopic antidiuretic hormone production had a poor prognosis even if they had achieved a complete response. Only one partial response to VP-16-213 occurred. There was a strong correlation between initial intrathoracic tumor size as assessed by total cross-sectional area on CT scan and response and survival. When the total area exceeded 30 cm2 there were no complete responders, but there were complete responses in eight of 21 patients when the area was less than 30 cm2. The relationship between intrathoracic tumor size and response rate was present when analyzed according to disease extent, age, sex, and performance status. A clear relationship between total tumor area and survival was also found. When SCCB is treated with chemotherapy alone, the prognosis is better for those patients who present with limited disease, without SIADH, and with small intrathoracic tumor. In this group it is possible that further intensification of therapy may result in prolonged survival.

Topics: Adult; Aged; Antineoplastic Agents; Carcinoma, Small Cell; Cyclophosphamide; Drug Therapy, Combination; Etoposide; Female; Humans; Inappropriate ADH Syndrome; Leucovorin; Lomustine; Lung Neoplasms; Male; Methotrexate; Middle Aged

5 patients with small-cell lung cancer were treated with high-dose methotrexate (1.75-16 g). No significant tumor reduction could be demonstrated. High-dose methotrexate therapy cannot be recommended for the treatment of small-cell lung cancer. Other established and successful regimens are available.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Humans; Leucovorin; Lung Neoplasms; Male; Methotrexate; Middle Aged; Vincristine

Topics: Carcinoma, Bronchogenic; Cisplatin; Cyclophosphamide; Drug Therapy, Combination; Humans; Leucovorin; Lomustine; Lung Neoplasms; Methotrexate

A 13-year-old girl was treated surgically for a giant-cell tumor of bone originating in the talus and for a recurrence in the distal tibia. She later developed liver and lung metastases and was treated for two years, five months with a combination of vincristine, doxorubicin, cyclophosphamide and actinomycin-D, and thereafter with high-dose methotrexate/vincristine with citrovorum factor rescue. A good response was obtained and the patient is without evidence of disease 12 months after a salvage thoracotomy for residual disease in the left lung. Aspects of this singular case are discussed.

Topics: Adolescent; Antineoplastic Agents; Bone Neoplasms; Drug Therapy, Combination; Female; Giant Cell Tumors; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Methotrexate; Talus; Tibia; Vincristine

Of 12 adult patients with high-grade soft tissue sarcoma receiving adjuvant chemotherapy and at risk for 36-84 months, 9 (75%) remain metastasis free and 10 (83%) have adequate local disease control with limb preservation. This is significantly better (P greater than 0.015) than a comparable "historic" control of 48 previously treated patients. The results correlate well with the few similar studies reported.

Topics: Adult; Aged; Antineoplastic Agents; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Leucovorin; Lung Neoplasms; Male; Methotrexate; Middle Aged; Neoplasm Recurrence, Local; Pilot Projects; Radiography; Sarcoma; Vincristine

A phase II study of metoprine in low dose and in high dose with citrovorum rescue was conducted in patients with non-small-cell lung carcinoma. There were no responses observed in the 36 patients studied, yielding a predicted true response rate of less than 9%. Thrombocytopenia was the dose-limiting toxicity of the low-dose regimen; there was also one episode of leukopenia and sepsis in this group. Although citrovorum rescue obviated hematologic toxicity in the high-dose regimen, mild to moderate neurological toxicity occurred at this dose. Metoprine does not appear to be a useful agent in non-small-cell lung carcinoma when used in the dose schedule employed in this study.

Topics: Adult; Aged; Antineoplastic Agents; Drug Evaluation; Female; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Pyrimethamine

From 1972 to 1979, high-dose methotrexate (HDMTX) and 3 adjuvant regimens were used at the Sidney Farber Cancer Institute and Children's Hospital Medical Center. In the first regiment, HDMTX was used alone; the second, HDMTX and adriamycin, and the third, weekly courses of HDMTX and combination. Actuarial disease-free survival achieved with these regimens in patient with local control of the primary lesion varied from 42 to 75% at 3 years. This compared favorably with historical control patients, of whom 50% were free of disease at 6 months and only 20% at 12 months. Among 41 patients with established pulmonary metastases, 14 were alive and free of disease from more than 4 to over 60 months. The most efficacious method of administering HDMTX was a weekly schedule which produced an overall response rate of 48% in the treatment of pulmonary metastases and primary tumor in patients previously not exposed to HDMTX. Urinary alkalinization was not a standard procedure, and investigations failed to demonstrate any significant effect of alkalinization on HDMTX pharmacokinetics.

Topics: Antineoplastic Agents; Bone Neoplasms; Child; Doxorubicin; Humans; Kinetics; Leucovorin; Lung Neoplasms; Methotrexate; Osteosarcoma; Vincristine

Topics: Amputation, Surgical; Antineoplastic Agents; Bone Neoplasms; Doxorubicin; Drug Therapy, Combination; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Osteosarcoma; Probability; Time Factors; Vincristine

Topics: Amputation, Surgical; Antineoplastic Agents; Bone Neoplasms; Doxorubicin; Drug Evaluation; Drug Therapy, Combination; Humans; Immunization; Leucovorin; Lung Neoplasms; Methotrexate; Osteosarcoma

Review of the reported use of high-dose methotrexate (HDMTX) with citrovorum factor rescue (CF) for treatment of primary and metastatic osteosarcoma indicates the rarity of responses in clinical situations other than treatment of the primary tumor or isolated pulmonary metastases with doses of 7.5 g/m2 or greater delivered on a weekly basis for 4 to 6 weeks. Adjuvant chemotherapy using HDMTX-CF at triweekly intervals has led to 2-year disease-free survival rates that are inferior to those obtained with combinations of agents including HDMTX-CF Adriamycin (Adria), with or without vincristine, cyclophosphamide, phenylalanine mustard, bleomycin, and dactinomycin. We concluded that although HDMTX-CF has a role in the treatment of primary and metastatic osteosarcoma, its use in combination with other active agents offers greater potential advantage to affected patients.

Topics: Antineoplastic Agents; Bone Neoplasms; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Osteosarcoma; Prognosis; Vincristine

Under the aegis of the Queensland Trophoblastic Tumour Registry, a screening and monitoring programme with the beta-subunit of chorionic gonadotrophin as a marker was adopted in the management of patients with gestational trophoblastic disease. Twenty-six patients had been treated with pulses of methotrexate, followed by folinic acid rescue, up to a total dose of 200 mg of methotrexate in each course; the side effects were minor and infrequent. This regimen was effective in producing biochemical and clinical remission in 18 of 19 patients both with non-metastatic and with metastatic persistent disease; the mean duration of treatment was nine weeks and 19.2 weeks respectively. However, it was effective in only three of seven patients with histologically confirmed choriocarcinoma, which suggests that a more aggressive multidrug regimen should be considered from the outset in this high risk group of patients. Our preliminary data have revealed no permanent effects on subsequent fertility or observable effects on the babies so far studied.

Topics: Choriocarcinoma; Chorionic Gonadotropin; Drug Therapy, Combination; Female; Humans; Injections, Intramuscular; Leucovorin; Lung Neoplasms; Methotrexate; Peptide Fragments; Pregnancy; Trophoblastic Neoplasms; Uterine Neoplasms

High-dose methotrexate and Leucovorin (calcium folinate) rescue was evaluated as induction chemotherapy in combination with cyclophosphamide, doxorubicin, and vincristine in 21 patients with extensive-stage small cell lung cancer. Nine (42%) of 21 had a complete remission. The median duration of remission has been short (5 months), and attempts are now under way to improve consolidation chemotherapy. In general, the degree of myelotoxicity was not increased by the high-dose methotrexate, although the antitumor activity of the combination appears enhanced. Attempts at further increasing the intensity of this regimen or comparative trials with other therapy appears warranted.

Topics: Adult; Aged; Carcinoma, Small Cell; Drug Therapy, Combination; Female; Humans; In Vitro Techniques; Leucovorin; Lung Neoplasms; Male; Methotrexate; Middle Aged

Methotrexate (MTX) in high doses (3 to 7.5 g/m2) with leucovorin rescue (HDMTX-LCV) can be delivered on a weekly basis in a setting of proper pharmacologic monitoring. Myelosuppression occurs in 28 per cent of the patients and in 8 per cent of the courses and usually results from delayed MTX excretion secondary to mild reversible nephrotoxicity. The incidence of tumor regression was 50 per cent in head and neck cancer; 59 per cent in non-Hodgkin's lymphoma; 40 per cent in small cell lung cancer; 24 to 50 per cent in breast cancer and 50 per cent in osteogenic carcinoma, for an over-all response rate of 39 per cent (70 of 178) in patients with disseminated cancer. HDMTX-LCV is not recommended for the conventional treatment of metastatic cancer because of the potential for toxicity and the fact that the response rates cited are probably not superior to those which can be achieved by conventional doses of MTX. However, the relative lack of myelosuppression and mucositis, when compared to conventional unrescued MTS, and the achievement of therapeutic concentrations of MTX in the central nervous system with the HDMTX-LCV program have led to its incorporation into clinical trials of combination chemotherapy.

Topics: Adult; Bone Marrow; Bone Neoplasms; Breast Neoplasms; Drug Administration Schedule; Female; Gastrointestinal Neoplasms; Head and Neck Neoplasms; Humans; Kidney; Leucovorin; Lung Neoplasms; Lymphoma; Methotrexate; Neoplasms; Urogenital Neoplasms

The case of a six year old girl with metastatic (or primarily multifocal) osteogenic sarcoma is reported, which was treated with chemotherapy only. Within 15 months--the primary tumor regressed and at least a transient inactivation has resulted until now;--the pulmonary metastases showed no progression;--an osteoplastic destruction of the sacrum has completely regressed. At the time of report (15 months after initiation of treatment) neither on X-ray controls nor on bone scan signs of tumor regrowth are evident. The child is without any complaints and the leg has no loss of function.

Topics: Antineoplastic Agents; Child; Doxorubicin; Drug Therapy, Combination; Female; Femoral Neoplasms; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Neoplasm Metastasis; Osteosarcoma; Radiography; Remission, Spontaneous; Sacrum; Vincristine

Topics: Antineoplastic Agents; Cell Count; Cell Survival; Child; Drug Resistance; Drug Therapy, Combination; Female; Humans; Kinetics; Leucovorin; Lung Neoplasms; Male; Methotrexate; Neoplasm Metastasis; Osteosarcoma

Biopsy specimens from a 21-year-old man showed mycosis fungoides involving the skin and lungs. Usually such a case represents a fulminant and fatal course of the disease. This patient had a complete remission of his pulmonary disease following sequential therapy with cyclophosphamide, vincristine sulfate, methotrexate, leucovorin calcium, and cytarabine (COMLA).

Topics: Adult; Cyclophosphamide; Cytarabine; Drug Therapy, Combination; Humans; Leucovorin; Lung Neoplasms; Male; Methotrexate; Mycosis Fungoides; Remission, Spontaneous; Skin Neoplasms; Vincristine

Thirteen patients with metastatic squamous cell cancer of the lung were treated, in a nonrandomized study, with an oral high-dose methotrexate and citrovorum factor rescue regimen. There was some response and/or stabilization of disease for at least three months in six (46%) of 13 cases. The median survival time of the study group was double (365 vs. 180 days) that of a retrospectively matched control group. This suggests a possible therapeutic effect of this treatment program in metastatic squamous cell cancer of the lung.

Topics: Administration, Oral; Adult; Aged; Carcinoma, Squamous Cell; Drug Therapy, Combination; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Middle Aged; Neoplasm Metastasis; Remission, Spontaneous; Time Factors

Topics: Child; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Drug Therapy, Combination; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Neoplasm Metastasis; Osteosarcoma

The occurrence of pulmonary metastases in patients suffering from primary classic osteogenic sarcoma is compared among two groups of patients treated according to different protocols at Groote Schuur Hospital. A group of 28 patients treated by radiation and delayed amputation (before the end of 1974) is compared with 12 patients managed by immediate ablation and adjuvant chemotherapy with vincristine, high-dose methotrexate and leucovorin rescue, and adriamycin (after 1974). The incidence of pulmonary metastases at 12 months was significantly lower in the latter group.

Topics: Adolescent; Adult; Bone Neoplasms; Child; Child, Preschool; Doxorubicin; Extremities; Female; Humans; Leucovorin; Lung Neoplasms; Male; Methotrexate; Neoplasm Metastasis; Osteosarcoma; Vincristine

Topics: Adenocarcinoma; Administration, Oral; Antineoplastic Agents; Bone Marrow; Depression, Chemical; Humans; Kidney Neoplasms; Leucovorin; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Pyrimethamine

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Antineoplastic Agents; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cell Cycle; Cell Survival; Drug Therapy, Combination; Humans; Kinetics; Leucovorin; Lung Neoplasms; Methotrexate

Vincristine-high-dose methotrexate-citrovorum factor (VCR-MTX-CF) was administered preoperatively at weekly intervals to eight patients, four with primary tumors and four with pulmonary metastases. These patients had not received prior VCR-MTX-CF treatment. A similar treatment program was administered to five patients with pulmonary metastases who had received prior VCR-MTX-CF. Among the eight patients who had not received prior VCR-MTX-CF, complete responses were obtained in three with primary tumors (this was followed by surgical excision) and two with pulmonary metastases. Partial responses occurred in two additional patients. Partial responses were also obtained in two patients who had received VCR-MTX-CF. Chemotherapy and surgery in one patient with an extremity lesion resulted in preservation of the limb and useful function. The major toxicity was anorexia and weight loss. Other side effects included stomatitis, myelosuppression, hepatitis and transient renal impairment. The weekly program was highly effective when compared to responses obtained with the tri-weekly schedule utilized in previous studies.

Topics: Bone Neoplasms; Drug Administration Schedule; Humans; Leucovorin; Lung Neoplasms; Male; Methotrexate; Neoplasm Metastasis; Osteosarcoma; Remission, Spontaneous; Vincristine

Results of treatment for osteosarcoma of the extremity have been poor with metastases usually causing death within 2 years following diagnosis. Because of the great risk of development of metastases, 20 patients have received adjuvant chemotherapy with Adriamycin, cyclophosphamide and high-dose methotrexate-leucovorin rescue for up to 12 months following amputation for osteosarcoma. Sixteen of these patients are surviving; 11 are free of evident tumor from 6 to 34 months following amputation. Five patients were found to have pulmonary metastases while receiving chemotherapy and three patients developed metastases following completion of chemotherapy. One patient died following her third treatment with high-dose methotrexate-leucorovin rescue. Other toxicity included nausea, vomiting, mucosal ulcerations, infections, hematologic abnormalities, changes in kidney and liver functions tests, and minor coagulation abnormalities. The natural history of osteosarcoma may have been modified by the use of these agents for periods exceeding the median time to predicted detection of pulmonary metastases. Microscopic metastases of some patients were eradicated by this adjuvant chemotherapy. For patients who developed metastases, these metastases were delayed in their time of detection and in their number at the time of detection.

Topics: Adolescent; Adult; Amputation, Surgical; Antineoplastic Agents; Bone Neoplasms; Child; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Drug Therapy, Combination; Extremities; Female; Humans; Leucovorin; Lung Neoplasms; Male; Methotrexate; Neoplasm Metastasis; Osteosarcoma

Topics: Adolescent; Adult; Aged; Child; Chondrosarcoma; Cyclophosphamide; Doxorubicin; Female; Femoral Neoplasms; Femur; Humans; Leucovorin; Lung Neoplasms; Male; Methotrexate; Middle Aged; Neoplasm Metastasis; Osteosarcoma; Postoperative Complications; Prostheses and Implants; Vincristine

Topics: Animals; Asparaginase; Breast Neoplasms; Carboxypeptidases; Child; Drug Administration Schedule; Drug Therapy, Combination; Female; Gastrointestinal Neoplasms; Genital Neoplasms, Female; Head and Neck Neoplasms; Humans; Leucovorin; Leukemia; Lung Neoplasms; Lymphoma; Melanoma; Methotrexate; Neoplasms; Osteosarcoma; Tetrahydrofolates; Thymidine

Vincristine (VCR), high-dose methotrexate (MTX), and citrovorum factor (CF) were administered to 12 patients with classic osteogenic sarcoma with local control. Seven patients (58%) are free of pulmonary metastases for 2+-31/2+ years. With a second adjuvant program incorporating adriamycin (VCR, MTX, CF, and adriamycin), 16 of 20 patients are free of pulmonary metastases for 6+-18+ months. Five patients who developed pulmonary metastases were rendered free of disease by surgical resection. The VCR, MTX, and CF program was also administered at weekly intervals to eight patients with pulmonary metastases or unresected primary lesions. Two complete and one partial response were obtained in four patients with pulmonary metastases and three complete and one partial response were obtained in patients with primary lesions. This program was also administered in combination with radiation therapy to four patients who relapsed on conventional VCR, MTX, CF, and adriamycin therapy following surgical resection of pulmonary metastases. They remain free of recurrent disease for 2+-14+ months. There was no alteration in the incidence of toxicity when compared to earlier investigations. The results indicate that the VCR, MTX, and CF program has had a major impact on the management of osteogenic sarcoma.

Topics: Doxorubicin; Drug Administration Schedule; Drug Therapy, Combination; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Neoplasm Metastasis; Osteosarcoma; Vincristine

The combination of adriamycin, 5-fluorouracil and methotrexate with folinic acid reversal was used to treat patients with advanced bronchogenic carcinoma. Twenty-one of 30 patients showed an objective response. This combination appears to produce useful remissions in patients with non-squamous lung cancer.

Topics: Carcinoma, Bronchogenic; Doxorubicin; Drug Therapy, Combination; Female; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Methotrexate; Middle Aged; Remission, Spontaneous; Time Factors

Topics: Adult; Choriocarcinoma; Female; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Neoplasm Metastasis; Pregnancy; Uterine Neoplasms

Two patients with osteogenic sarcoma of the proximal tibia were treated pre-operatively with intensive chemotherapy with high dose methotrexate (HDMTX) with citrovorum factor rescue (CFR) and adriamycin (ADR). One patient died before surgery. The other underwent en bloc resection of the primary tumor with prosthetic replacement of the involved tibia, following by adjuvant chemotherapy consisting of HDMTX with CFR and ADR, but died of metastases. Complete control of the primary or metastatic tumor was not achieved. It is emphasised that intensive multiple drug chemotherapy should be administered with extreme caution. The histologic findings are carefully analysed in relation to objective tumor response and toxic chemotherapy effects.

Topics: Adolescent; Antineoplastic Agents; Bone Neoplasms; Doxorubicin; Drug Therapy, Combination; Female; Humans; Leucovorin; Lung Neoplasms; Male; Methotrexate; Neoplasm Metastasis; Osteosarcoma; Tibia

We have reviewed the literature and described experience in treating Ewing's sarcoma and osteosarcoma before and during the era of intensive systemic chemotherapy. Local control of Ewing's sarcoma may relate to increasing doses of radiation, especially when intensive chemotherapy is administered also. Problems of radiation enhancement by chemotherapy have caused us to reconsider time-dose and volume parameters in treating these patients. The role of radiation in osteogenic sarcoma is limited to patients with inoperable lesions and metastases.

Topics: Bone Neoplasms; Child; Cyclophosphamide; Dactinomycin; Doxorubicin; Drug Therapy, Combination; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Neoplasm Metastasis; Osteosarcoma; Radiation Tolerance; Radiotherapy Dosage; Radiotherapy, High-Energy; Sarcoma, Ewing; Vincristine

Ten patients with metastatic osteosarcoma were treated at the Joint Center for Radiation Therapy, the Sidney Farber Cancer Institute, and the Children's Hospital Medical Center from 1973 to 1976. Patients were treated with an aggressive multimodality approach with included surgery, chemotherapy, and radiation therapy. Three of 10 patients are alive with no evidence of disease, five are alive, with disease, and two are dead of disease. The median survival is 12+ months. Local control data for radiation combined with high dose methotrexate in metastatic osteosarcoma is shown.

Topics: Adolescent; Adult; Female; Humans; Leucovorin; Lung Neoplasms; Male; Methotrexate; Neoplasm Metastasis; Osteosarcoma; Prognosis; Radiotherapy, High-Energy

A 21-year-old patient with metastatic osteosarcoma was receiving methotrexate with leucovorin rescue every 2 weeks. After the second (of four) infusions of methotrexate, a prior solar burn on an area of skin was reactivated in spite of leucovorin rescue. An area of skin treated 5 months previously by radiation was spared the effects of the reactivation phenomenon. No other toxicities appeared. The reactivation of the solar burn is an example of "false photosensitization" and this cutaneous toxicity is not ameliorated by leucovorin. Methotrexate therapy should be delayed until the effects of generalized solar burns have resolved (approximately 1 week).

Topics: Adult; Humans; Leucovorin; Lung Neoplasms; Male; Methotrexate; Osteosarcoma; Skin; Sunburn

Using a co-ordinated multidisciplinary approach with surgery, radiation therapy, and chemotherapy, 14 out of 21 patients with metastases from osteogenic sarcoma were rendered free of disease for over two to over 18 months. Most patients had pulmonary metastases, two had bony metastases, and one had metastases in the iliac nodes. As part of this multidisciplinary approach weekly high-dose methotrexate was given and caused tumour regression in seven out of 15 patients. After all clinical evidence of disease had been removed high-dose methotrexate was administered every two to three weeks as maintenance treatment. To assess the efficacy of treatment the results were compared with those in a historical control group of 82 consecutive patients who developed pulmonary or other metastases. The results in the study group were significantly better. This experience may be similar to that in Wilms's tumour, where actinomycin D has increased the cure rate when administered as adjuvant therapy after treatment of localised or overt metastatic disease.

Topics: Adolescent; Adult; Bone Neoplasms; Child; Doxorubicin; Female; Humans; Leucovorin; Lung Neoplasms; Lymph Node Excision; Lymphatic Metastasis; Male; Methotrexate; Neoplasm Metastasis; Osteosarcoma; Radiotherapy Dosage; Vincristine

Methodichlorophen was given to 26 patients with terminal malignant disease. Eight patients received adequate doses, and five of them showed objective evidence of tumour regression while three failed to respond. Those who responded included four out of five patients with lung cancer (three with squamous-cell carcinoma and one with oat-cell carcinoma) and a patient with hypernephroma. Two patients with testicular teratomas and one with acute myeloid leukemia failed to respond. The drug may be given safely by mouth to outpatients if certain precautions are taken.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents; Bone Marrow Diseases; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Chlorobenzenes; Drug Therapy, Combination; Erythema; Headache; Humans; Kidney Neoplasms; Leucovorin; Leukemia, Myeloid, Acute; Lung Neoplasms; Male; Middle Aged; Neoplasms; Pyrimethamine; Pyrimidines; Teratoma; Testicular Neoplasms

This report concerns a consecutive group of 10 children with metastatic osteogenic sarcoma treated with combined surgery and chemotherapy. Eight of 10 patients had thoracotomy prior to chemotherapy, and 2 after an initial trial of chemotherapy. Sequential chemotherapy was given to all patients and consisted of vincristine, high-dose methotrexate with citrovorum factor rescue, cyclophosphamide, and Adriamycin. Chemotherapy was continuously recycled for 1 year. The encouraging results obtained with these 10 patients are demonstrated with emphasis on the value of aggressive multidisciplinary therapy in salvaging patients with advanced metastatic osteogenic sarcoma.

Topics: Adolescent; Antineoplastic Agents; Child; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Neoplasm Metastasis; Osteosarcoma; Vincristine

Fourteen patients with 16 metastatic ostogenic sarcoma lesions were treated with high-dose methotrexate (HDMTX) with citrovorum factor rescue (CFR), adriamycin, and pulse high-dose cyclophosphamide combined with radiation therapy. Thirteen of 16 lesions responded. Responses consisted of relief of pain (6/6 patients) in bone lesions, roentgenographic and clinical evidence of decrease in the size of the bone lesions (6/7 patients), and a decrease in the size of pulmonary metastases (2/4 patients). The 2 patients whose pulmonary metastases responded to combined therapy developed pulmonary fibrosis and pneumonitis in the treated areas 3 months after radiation therapy (RT) (1400 and 1600 rads respectively). Of two bulky primary tumors that appeared to respond, both were ultimately found to contain viable tumor; a third less bulky primary tumor appeared to respond more completely. Three smaller metastatic bone lesions that were ultimately biopsied showed no evidence of active tumor. It is concluded that: 1) combination therapy (particularly HDMTX and RT) has an additive effect in controlling osteogenic sarcoma bone lesions, but bulky primary tumors cannot be completely eradicated; 2) although synergistic in treating osteogenic sarcoma, combination therapy can produce enhanced toxicity in surrounding normal lung tissue; and 3) combination therapy is of value in the palliative treatment of metastatic lesions other than that of lung, and in the treatment of small primary bone lesions. However, experience to date does not justify the delay in surgical ablation of a primary lesion in a child who presents without metastatic disease.

Topics: Adolescent; Antineoplastic Agents; Child; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Neoplasm Metastasis; Osteosarcoma; Pneumonia; Pulmonary Fibrosis; Spinal Cord Compression

Topics: Adult; Animals; Biological Transport; Bone Marrow; Creatinine; DNA, Neoplasm; Doxorubicin; Drug Therapy, Combination; Humans; Kidney; Leucovorin; Leukemia L1210; Lung Neoplasms; Methotrexate; Mice; Neoplasm Metastasis; Neoplasms; Osteosarcoma; Purines; Thymidine; Thymine Nucleotides

The survival times in a control series of 145 cases of osteogenic sarcoma without pulmonary resections including records of pulmonary nodules and surgical wedge excisions, suggest that pulmonary resection is a noteworthy adjunct treatment. The 5-year survival of patients subjected to repeated pulmonary surgery is known for 22 patients who were under the age of 21. Where aggressive pulmonary resections were performed, i.e., repeated thoracotomies, and multiple wedge resections of nodules, a 5-year survival rate of 31 per cent (after date of primary amputation) is noted and compared to a previous study of 145 cases, 121 of which had untreated pulmonary metastases, and at 5 years, only 2 per cent of these patients with metastases were still alive. Lung wedge resection survivals are highly significant statistically although survival with residual disease must be considered in part at least, due to aggressive chemotherapy (i.e., high dose methotrexate with citrovorum rescue in combination with other drugs).

Topics: Bone Neoplasms; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Neoplasm Metastasis; Osteosarcoma

Topics: Amputation, Surgical; Doxorubicin; Drug Therapy, Combination; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Neoplasm Metastasis; Osteosarcoma

Topics: Adolescent; Adult; Bone Marrow; Bone Neoplasms; Child; Dose-Response Relationship, Drug; Humans; Kidney; Leucovorin; Lung Neoplasms; Methotrexate; Neoplasm Metastasis; Osteosarcoma; Radiotherapy Dosage; Skin; Stomatitis

Topics: Adenocarcinoma; Adult; Bone Marrow Diseases; Carcinoma, Squamous Cell; Humans; Leucovorin; Lung Neoplasms; Male; Methotrexate; Radiography

Topics: Adolescent; Adult; Aged; Carcinoma, Squamous Cell; Child, Preschool; Choriocarcinoma; Chorionic Gonadotropin; Female; Humans; Infusions, Parenteral; Injections, Intravenous; Leucovorin; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Lung Neoplasms; Male; Methotrexate; Middle Aged; Pregnancy; Teratoma; Testicular Neoplasms

Topics: Agranulocytosis; Antineoplastic Agents; Breast Neoplasms; Female; Hemangiosarcoma; Hodgkin Disease; Humans; Kidney Neoplasms; Leucovorin; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Lung Neoplasms; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Melanoma; Methotrexate; Osteosarcoma; Pancreatic Neoplasms; Radiography; Rectal Neoplasms; Rhabdomyosarcoma; Testicular Neoplasms; Thrombocytopenia

Topics: Antimetabolites; Antineoplastic Agents; Bone Marrow; Carcinoma, Bronchogenic; Humans; Infusions, Intra-Arterial; Injections, Intra-Arterial; Leucovorin; Lung Neoplasms; Lymphatic Metastasis; Mouth Neoplasms; Neoplasms; Pelvic Neoplasms; Radiography; Tongue Neoplasms; Tonsillar Neoplasms

Topics: Brain Neoplasms; Chemotherapy, Cancer, Regional Perfusion; Head and Neck Neoplasms; Humans; Leucovorin; Lung Neoplasms; Melanoma; Methotrexate; Neoplasms; Palliative Care; Pelvic Neoplasms