levoleucovorin and Leukopenia

To conduct a systematic literature review and meta-analysis to estimate the incidence of anaemia, leucopoenia, neutropenia and thrombocytopenia associated with MTX plus folic acid among patients with rheumatic diseases.. We searched MEDLINE, PubMed and EMBASE through August 2016 for all randomized controlled clinical trials with a MTX monotherapy arm. We excluded randomized controlled clinical trials for cancer and included only double-blind studies that reported on haematologic adverse events. Studies were excluded if patients did not receive folic acid or leucovorin supplementation. Full text articles were assessed by two independent reviewers. Incidence estimates were calculated using random-effects models.. Of 1601 studies identified, 30 (1.87%) were included, representing 3858 patients; all had RA. Seventeen trials reported on anaemia (n = 2032), 17 reported on leucopoenia (n = 2220), 16 reported on neutropenia (n = 2202) and 12 reported on thrombocytopenia (n = 1507). The incidence for any anaemia was 2.55% (95% CI 0.60-5.47%), any leucopoenia 1.17% (95% CI 0.16-2.80%), any neutropenia 1.77% (95% CI 0.33-4.00%), and any thrombocytopenia 0.19% (95% CI 0.00-0.86%). Four cases of severe anaemia were reported, as defined by authors, along with three cases of severe neutropenia. No cases of severe leucopoenia, severe thrombocytopenia or pancytopenia were reported.. Cytopenias are an uncommon side effect of low-dose MTX with folic acid supplementation among RA patients. Further research is needed to reach a more precise estimate.

Topics: Anemia; Antirheumatic Agents; Arthritis, Rheumatoid; Folic Acid; Humans; Leucovorin; Leukopenia; Methotrexate; Neutropenia; Pancytopenia; Randomized Controlled Trials as Topic; Rheumatic Diseases; Severity of Illness Index; Thrombocytopenia; Vitamin B Complex

The aim of this study was to evaluate systematically the efficacy and safety of oral uracil-tegafur (UFT) plus leucovorin (LV) compared with infusional fluorouracil (5-FU) plus LV for advanced colorectal cancer.. Eligible studies were identified from Medline, Embase and the Cochrane Library. The end-points included overall survival and overall tumour response rate, and toxicity including leucopenia, febrile neutropenia, stomatitis/mucositis and diarrhoea.. Five randomized controlled trials were identified. Pooled data demonstrated no difference in overall survival between the oral UFT plus LV regimen and the 5-FU bolus plus LV regimen [hazard ratio 1.013; 95% confidence interval (CI) 0.911-1.127].The fixed-effect pooled estimate for overall tumour response rate showed no significant difference between the two regimens (relative risk 0.893; 0.672-1.187). Grade 3-4 leucopenia [odds ratio (OR) 0.126; 955 CI 0.048-0.326], grade 1-4 leucopenia (OR 0.089; 95% CI 0.067-0.119) and grade1-4 febrile neutropenia (OR 0.020; 95% CI 0.004-0.102) were significantly less prominent in the oral UFT regimens. For nonhaematological toxicities, grade 3-4 stomatitis/mucositis (OR 0.075; 95% CI 0.039-0.146), grade 3-4 infection (OR 0.484; 95% CI 0.310-0.758), grade 1-4 infection (OR 0.672; 95% CI 0.547-0.826, P < 0.001), grade 1-4 diarrhoea (OR 0.743; 95% CI 0.626-0.881) were also less likely to happen in patients in the oral UFT plus LV regimen, while there was no significant difference between the two treatment regimens with respect to grade 1-4 stomatitis/mucositis (OR 0.278; 95% CI 0.053-1.456) and grade 3-4 (OR 1.174; 95% CI 0.983-1.403) diarrhoea.. Oral UFT or 5-FU bolus combined with LV results in similar overall survival and tumour response rates for advanced colorectal cancer. The former treatment regimen is greatly superior in terms of toxicity, especially haematological toxicity.

Topics: Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Diarrhea; Fluorouracil; Humans; Infections; Leucovorin; Leukopenia; Mucositis; Neutropenia; Odds Ratio; Randomized Controlled Trials as Topic; Stomatitis; Survival Analysis; Tegafur; Uracil

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Camptothecin; Clinical Trials as Topic; Colorectal Neoplasms; Diarrhea; Fluorouracil; Humans; Irinotecan; Leucovorin; Leukopenia; Nausea; Stomatitis; Thrombocytopenia; Vomiting

A 13-year-old girl with osteosarcoma and pulmonary metastases developed life-threatening renal toxicity, encephalopathy, and bone marrow failure following high dose methotrexate therapy. After successful treatment, high dose methotrexate therapy was continued without further problems. Recommendations for the prevention and the current management of methotrexate toxicity are discussed.

Topics: Adolescent; Blood Transfusion; Brain; Dose-Response Relationship, Drug; Female; Fluid Therapy; Furosemide; Humans; Kidney; Leucovorin; Leukopenia; Methotrexate; Osteosarcoma

Cancer progression is associated with significant systemic clinical manifestations including cachexia induced weight loss and anorexia. Pentoxifylline (PTX) is a drug that has been shown to have multiple beneficial effects in cancer patients through its anti-inflammatory properties.. To evaluate PTX effects on colon cancer patients treated with chemotherapy.. Forty metastatic colon cancer patients receiving chemotherapy were enrolled in this randomized study. 17 patients were treated with a full dose of PTX (400 mg TID), 9 patients with a reduced dose PTX (200 mg TID) and 23 served as controls (no PTX).. Follow-up evaluations of patients included the following: physical examination; leukopenia determination; weight determination; stomatitis determination; and survival rate. Patients treated with PTX (both full and reduced doses), experienced a significant increase in weight and a reduction in stomatitis relative to the control group. Treatment with PTX also significantly increased patient survival rate. All patients treated with PTX, had a median overall survival (OS) rate of 20.4 months as compared to 13.2 months in the control group.. PTX treatment of colon cancer patients, in addition to chemotherapy, significantly improved survival rates, induced weight gain and reduced stomatitis occurrence -all important parameters of cachexia.

Topics: Aged; Antineoplastic Agents; Cachexia; Colonic Neoplasms; Disease Progression; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Pentoxifylline; Stomatitis; Weight Gain

The purpose of this phase II study was to explore the efficacy and safety of an alternating regimen consisting of folinic acid, 5-fluorouracil (5-FU) and oxaliplatin (mFOLFOX6) plus bevacizumab, and folinic acid, 5-FU and irinotecan (FOLFIRI) plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer.. Fifty-two patients with metastatic colorectal cancer received an alternating regimen consisting of four cycles of mFOLFOX6 plus bevacizumab followed by four cycles of FOLFIRI plus bevacizumab until disease progression. The primary endpoint was progression-free survival.. The median age was 60 years (range 37-75 years). Median progression-free survival was 14.2 months (95 % confidence interval [CI] 10.6-16.3) and median overall survival was 28.4 months (95 % CI 22.6-39.1). The overall response rate was 60.0 % (95 % CI 45.2-73.6). Regarding toxicity, the commonest grade 3-4 hematological adverse events were neutropenia (34.6 %) and leukopenia (7.7 %), and the commonest grade 3-4 non-hematological adverse events were anorexia (13.5 %), fatigue (9.6 %), nausea (9.6 %), and vomiting (9.6 %). Bevacizumab-related grade 3-4 adverse events included hypertension (1.9 %) and thrombosis (1.9 %).. An alternating regimen consisting of mFOLFOX6 plus bevacizumab and FOLFIRI plus bevacizumab is an effective and well-tolerated first-line chemotherapy combination for patients with metastatic colorectal cancer.

Topics: Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colorectal Neoplasms; Disease-Free Survival; Fatigue; Female; Fluorouracil; Humans; Hypertension; Leucovorin; Leukopenia; Male; Middle Aged; Nausea; Neutropenia; Organoplatinum Compounds; Survival Rate; Thrombosis; Vomiting

The oral PI3K inhibitor BKM120 has been reported as safe and well tolerated in early phase clinical trials of advanced cancer patients. We performed a phase I trial of BKM120 plus mFOLFOX6 (5-FU/LV + oxaliplatin), a common chemotherapeutic backbone in GI malignancies, to establish the maximum tolerated dose (MTD) and characterize the safety and tolerability of the combination.. Patients with advanced solid tumors received oral BKM120 daily combined with standard doses of mFOLFOX6 every 2 weeks of a 28 day cycle. The study utilized a standard 3 + 3 dose escalation schema.. A total of 17 patients received treatment with BKM120, 13 of which were evaluate for dose limited toxicity (DLT). The most common tumor types were colorectal cancer, cholangiocarcinoma, pancreatic cancer and hepatocellular carcinoma. DLT included grade 3 hyperglycemia, grade 3 AST/ALT elevation, grade 4 neutropenia and grade 4 thrombocytopenia. A total of 76 % of patients experienced treatment related grade 3/4 adverse events (AEs), the most common of which were neutropenia, fatigue, leukopenia, hyperglycemia and thrombocytopenia. One patient demonstrated an unconfirmed partial response and three patients had stable disease.. The MTD of BKM120 in combination with standard doses of mFOLFOX6 was 40 mg daily, which is well below the 100 mg daily dose proven effective and tolerable both as a single agent and in combination with other chemotherapeutics. In addition, the regimen of BKM120 with mFOLFOX6 in patients with refractory solid tumors resulted in increased toxicity than would be expected from either the PI3K inhibitor or the chemotherapy backbone alone.

Topics: Administration, Oral; Adult; Aged; Aminopyridines; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Morpholines; Nausea; Neoplasms; Organoplatinum Compounds; Phosphoinositide-3 Kinase Inhibitors

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

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

To investigate whether infusional high-dose 5-flurouracil (HD-FU) provides a significant improvement in recurrence-free survival (RFS) and overall survival (OS) compared with a standard bolus 5-FU regimen (Mayo Clinic) in patients with curatively resectable stage III colon cancer.. Patients (n=1601) were randomised to receive either the Mayo Clinic regimen or one of the three HD-FU regimens; LV5FU2, the Arbeitsgemeinschaft Internistische Onkologie (AIO) or the Grupo Espaňol para el Tratamiento Digestivos (TTD), the data from which were combined to provide the HD-FU arm for final analysis.. Patients were evenly balanced for age, TMN, tumor grade and vascular and lymphatic invasion. Median follow-up was approximately 42months, RFS (hazard ratio [HR]=0.997) and OS (HR=0.96) (primary end-point) were not statistically different between the two treatment arms. Infusional HD-FU was generally better tolerated than bolus 5-FU regimen.. Infusional HD-FU does not improve RFS and OS in curatively resected stage III colon cancer patients compared to the Mayo Clinic regimen, but is less toxic.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colonic Neoplasms; Diarrhea; Dose-Response Relationship, Drug; Drug Administration Schedule; Europe; Female; Fluorouracil; Humans; Infusions, Intravenous; Kaplan-Meier Estimate; Leucovorin; Leukopenia; Male; Middle Aged; Neoplasm Staging; Treatment Outcome; Young Adult

This study aimed to compare the efficacy and toxicity of weekly paclitaxel plus S-1 with weekly paclitaxel plus 5-fluorouracil in treating advanced gastric cancer as first line regimen. The primary end-point was disease control rate (DCR).. Patients with advanced or recurrent gastric cancer were randomly assigned to an experimental arm or a control arm. The experimental arm's dosage schedule was paclitaxel 60 mg/m2 (intravenous infusion) on days 1, 8 and 15 and S-1 80-120 mg/d (oral administration) on days 1-14. Control arm patients were given the same paclitaxel, combined with 5-fluorouracil 500 mg/m2 (continuous intravenous infusion) on days 1-5; and leucovorin 20 mg/m2 (intravenous infusion) on days 1-5. All schedules were repeated every 28 d.. A total of 240 patients were enrolled and equally randomised into two arms. The overall response rate and DCR of the experimental arm was non-inferior to that of the control arm both in the per-protocol set and the full analysis set. The secondary end-point median progression-free survival (PFS) of the experimental and control arms was 153 and 129 d, with the hazard ratio of 0.641 (95% CI: 0.473-0.868, P = 0.004). The hazard ratio of the time to treatment failure of the two arms was 1.449 (95% CI: 0.705-2.980, P = 0.229). The six-month PFS rates of both arms were similar (31.3% versus 31.8%, P = 0.94). Cox regression analysis indicated that only treatment regimen and age were independent predictive factors for PFS. The most common adverse events were haematological and gastrointestinal. The rates of grade 3-4 adverse events were not significantly different between the two study arms and were mostly lower than 5%.. Weekly paclitaxel combined with S-1 is an active and well-tolerated regimen, supporting the view that S-1 can be an alternative for infusional 5-fluorouracil for advanced gastric cancer.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Drug Combinations; Female; Fluorouracil; Humans; Infusions, Intravenous; Kaplan-Meier Estimate; Leucovorin; Leukopenia; Male; Middle Aged; Multivariate Analysis; Nausea; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur; Treatment Outcome; Young Adult

The purpose of this multicenter phase II study was to evaluate the efficacy and safety of a combination of irinotecan, 5-fluorouracil (5-FU), and leucovorin (FOLFIRI) plus bevacizumab as first-line chemotherapy in Japanese patients with metastatic colorectal cancer.. Patients with metastatic colorectal cancer were eligible for enrollment. On day 1 of a 14-day cycle, patients received bevacizumab 5 mg/kg, irinotecan 150 mg/m², and L-leucovorin 200 mg/m² as an intravenous infusion, followed by 5-FU 400 mg/m² as an intravenous bolus and then 5-FU 2,400 mg/m² as an 46-h intravenous infusion. This treatment cycle was repeated. The primary endpoint was progression-free survival (PFS).. We enrolled 40 patients, but one withdrew consent before starting treatment. The remaining 39 patients received a total of 509 cycles of FOLFIRI plus bevacizumab (median 11 per patient; range 1-30). The median PFS was 11.5 months, the median overall survival (OS) was 22.0 months, and the 1-year OS rate was 81.8 %. All 39 patients had adverse events. Grade 3 or 4 neutropenia and stomatitis occurred in 21 (53.9 %) and 4 (10.3 %) patients, respectively.. Our results suggest that FOLFIRI plus bevacizumab is a clinically effective regimen with a manageable toxicity profile as first-line chemotherapy in patients with metastatic colorectal cancer.

Topics: Adenocarcinoma; Adult; Aged; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colorectal Neoplasms; Female; Fluorouracil; Follow-Up Studies; Humans; Incidence; Japan; Leucovorin; Leukopenia; Liver Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Stomatitis; Survival Analysis

This study was designed to investigate the efficacy and safety of the epidermal growth factor receptor (EGFR) inhibitor cetuximab combined with irinotecan, folinic acid (FA) and two different doses of infusional 5-fluorouracil (5-FU) in the first-line treatment of EGFR-detectable metastatic colorectal cancer.. The 5-FU dose was selected on the basis of dose-limiting toxicities (DLTs) during part I of the study. Patients received cetuximab (400 mg/m2 initial dose and 250 mg/m2/week thereafter) and every 2 weeks irinotecan (180 mg/m2), FA (400 mg/m2) and 5-FU (either low dose [LD], 300 mg/m2 bolus plus 2,000 mg/m2 46-hour infusion, n = 7; or, high-dose [HD], 400 mg/m2 bolus plus 2,400 mg/m2; n = 45).. Only two DLTs occurred in the HD group, and HD 5-FU was selected for use in part II. Apart from rash, commonly observed grade 3/4 adverse events such as leucopenia, diarrhoea, vomiting and asthenia occurred within the expected range for FOLFIRI. Among 52 patients, the overall response rate was 48%. Median progression-free survival (PFS) was 8.6 months (counting all reported progressions) and the median overall survival was 22.4 months. Treatment facilitated the resection of initially unresectable metastases in fourteen patients (27%): of these, 10 patients (71%) had no residual tumour after surgery, and these resections hindered the estimation of PFS.. The combination of cetuximab and FOLFIRI was active and well tolerated in this setting. Initially unresectable metastases became resectable in one-quarter of patients, with a high number of complete resections, and these promising results formed the basis for the investigation of FOLFIRI with and without cetuximab in the phase III CRYSTAL trial.

Topics: Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cetuximab; Colorectal Neoplasms; Diarrhea; Disease Progression; Dose-Response Relationship, Drug; Drug Administration Schedule; Exanthema; Female; Fluorouracil; Follow-Up Studies; Humans; Infusions, Intravenous; Irinotecan; Leucovorin; Leukopenia; Male; Middle Aged; Neoplasm Metastasis; Survival Analysis; Treatment Outcome; Vomiting

The purpose of this study was to evaluate the effect of bevacizumab on the pharmacokinetics (PK) of irinotecan and its active metabolite. Exploratory analyses of the impact of variability in uridine diphosphate glucuronosyltransferase 1A (UGT1A) genes on irinotecan metabolism and toxicity were conducted.. This was an open-labeled, fixed-sequence study of bevacizumab with FOLFIRI (irinotecan, leucovorin, and infusional 5-fluorouracil). Pharmacokinetic assessments were conducted in cycles 1 and 3.. Forty-five subjects were enrolled. No difference in dose-normalized AUC(0-last) for irinotecan and SN-38 between irinotecan administered alone or in combination with bevacizumab was identified. Leukopenia was associated with higher exposure to both irinotecan and SN-38. UGT1A1 polymorphisms were associated with variability in irinotecan PK. Gastrointestinal toxicity was associated with UGT1A6 genotype. No other associations between UGT1A genotypes and toxicity were detected.. Bevacizumab does not affect irinotecan PK when administered concurrently. A variety of pharmacogenetic relationships may influence the pharmacokinetics of irinotecan and its toxicity.

Topics: Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Bevacizumab; Camptothecin; Drug Interactions; Female; Fluorouracil; Gastrointestinal Tract; Genotype; Glucuronosyltransferase; Humans; Irinotecan; Leucovorin; Leukopenia; Male; Middle Aged; Neoplasms; Pharmacogenetics; Polymorphism, Genetic; Prodrugs

To evaluate the efficacy and safety of the combination of oxaliplatin and ELF (VP16/CF/5-Fu) regimen in the treatment of patients with advanced gastric cancer.. Oxaliplatin was given at a dose of 100 mg/m(2) i.v. 2 hours D1, calcium folinate (CF) 200 mg/m(2) i.v. 1/2 hour D1 approximately D3, 5-fluorouracil (5-Fu) 500 mg/m(2) i.v. 2 hours D1 approximately D3 and etoposide 100 mg/m(2) i.v. 3 hours D1 approximately D3. Cycles were repeated every 21 days. Efficacy and safety were evaluated every 2 cycles.. Sixty-nine patients were enrolled into the study. All cases were pathologically confirmed as gastric cancer (adenocarcinoma in 57 cases and signet ring cell carcinoma in 12 cases). 42 patients had newly diagnosed disease, and 27 patients had received previous chemotherapy. 62 patients were analyzed for response (7 complete responses and 25 partial responses) with total response rate 51.61%. The median time to progression was 5.7 months and the median overall survival was 9.2 months. The most common hematologic toxicities were anemia (29.0%), leucopenia (51.2%) and thrombocytopenia (21.2%). No grade 4 and grade 5 hematologic toxicities were observed. The most common non-hematologic toxicities were nausea (46.5%), vomiting (41.1%), peripheral sensory neuropathy (47.1%), and grade 2 alopecia (27.3%).. This oxaliplatin combined with ELF regimen shows good efficacy and acceptable safety in advanced gastric cancer patients. It is worthy to be proved as a suitable alternative regimen in this indication.

Topics: Adenocarcinoma; Adult; Aged; Anemia; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Signet Ring Cell; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Levoleucovorin; Male; Middle Aged; Nausea; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Remission Induction; Stomach Neoplasms; Survival Rate; Thrombocytopenia; Vomiting

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

To assess the predictive value of polymorphisms in dihydropyrimidine dehydrogenase (DPYD ), thymidylate synthase (TYMS ), and methylene tetrahydrofolate reductase (MTHFR ) and of nongenetic factors for severe leukopenia, diarrhea, and mucositis related to fluorouracil (FU) treatment.. A multicenter prospective clinical trial included 683 patients with cancer treated with FU monotherapy. Toxicity was documented according to World Health Organization grades. DPYD, TYMS, and MTHFR genotypes were determined, and DPYD was resequenced in patients with severe toxicity.. Grade 3 to 4 toxicity occurred in 16.1% of patients. The sensitivity of DPYD*2A genotyping for overall toxicity was 5.5% (95%CI, 0.02 to 0.11), with a positive predictive value of 0.46 (95% CI, 0.19 to 0.75; P = .01). Inclusion of additional DPYD variants improved prediction only marginally. Analysis according to toxicity type revealed significant association of DPYD with mucositis and leukopenia, whereas TYMS was associated with diarrhea. Genotype, female sex, mode of FU administration, and modulation by folinic acid were identified as independent risk factors by multivariable analysis. A previously unrecognized significant interaction was found between sex and DPYD, which resulted in an odds ratio for toxicity of 41.8 for male patients (95% CI, 9.2 to 190; P < .0001) but only 1.33 (95% CI, 0.34 to 5.2) in female patients. Homozygosity for the TYMS enhancer region double repeat allele increased risk for toxicity 1.6-fold (95% CI, 1.08 to 2.22; P = .02).. DPYD, TYMS, and MTHFR play a limited role for FU related toxicity but a pronounced DPYD gene/sex-interaction increases prediction rate for male patients. Toxicity risk assessment should include sex, mode of administration, and folinic acid as additional predictive factors.

Topics: Antimetabolites, Antineoplastic; Diarrhea; Dihydrouracil Dehydrogenase (NADP); DNA Methylation; Female; Fluorouracil; Gene Frequency; Genetic Predisposition to Disease; Genetic Testing; Germany; Homozygote; Humans; Leucovorin; Leukopenia; Logistic Models; Male; Methylenetetrahydrofolate Reductase (NADPH2); Mucositis; Odds Ratio; Patient Selection; Polymorphism, Genetic; Predictive Value of Tests; Promoter Regions, Genetic; Prospective Studies; Risk Assessment; Risk Factors; Severity of Illness Index; Thymidylate Synthase; Vitamin B Complex

The aim of this study was to evaluate the efficacy and toxicity of concurrent chemoradiotherapy using cisplatin (CDDP), 5-fluorouracil (5-FU), methotrexate (MTX) and leucovorin (LV) (PFML) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN).. Seventy-seven patients with previously untreated stages III-IV SCCHN were included in this trial. Patients received two cycles of chemotherapy repeated every 4 weeks. The chemotherapy regimen consisted CDDP (60 mg/m2, day 4), 5-FU (600 mg/m2 given over 24 h for 5 days, days 1-5), MTX (30 mg/m2, day 1) and LV (20 mg/m2, days 1-5). Radiation was targeted to begin on the starting day of chemotherapy, day 1. The total radiation dose to the primary site and neck lymph nodes was 70.0 Gy. When grade>or=3 toxicities were observed frequently, radiotherapy and/or chemotherapy were delayed or reduced.. The main toxicities were mucositis (grade>or=3, 39%), leukocytopenia (grade>or=3, 34%) and neutropenia (grade>or=3, 30%). The overall clinical response rate and the pathological complete response (CR) were 94% (72/77) and 71% (55/77). The primary site CR and neck lymph node CR were 79% (61/77) and 85% (44/52), and 3-year survival rate was 73%.. This concurrent chemoradiotherapy with PFML was safe and well tolerated. The high CR rate justifies further evaluation of this chemoradiotherapy modality in locally advanced SCCHN patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Female; Fluorouracil; Head and Neck Neoplasms; Humans; Leucovorin; Leukopenia; Male; Methotrexate; Middle Aged; Mucositis; Neutropenia; Radiotherapy Dosage

Combination chemotherapy with 5-fluorouracil (5-FU) and cisplatin is regarded as the standard regimen for advanced esophageal carcinoma. This study was to evaluate the efficacy and safety of DLF, CLF and DFM regimens, based on platinum compound plus 5-fluorouracil in the treatment of advanced esophageal carcinoma, and to further explore prognostic factors of advanced esophageal carcinoma.. From October 1999 to December 2004, 98 patients with advanced esophageal carcinoma were enrolled in the study. They were non-randomly assigned to receive a 2-hour infusion of folinic acid 200 mg/m(2), followed by a 5-FU bolus 400 mg/m(2) and 48-hour infusion of 5-FU 3,000 mg/m(2) every 3 weeks, combined with cisplatin 80 mg/m(2) (DLF, n=48) or with carboplatin AUC=5 on day 1 (CLF, n=32), or with cisplatin 80 mg/m(2), 5-fluorouracil bolus 400 mg/m(2) on day 1-5 plus pingyangmycin 5 mg/m(2) on day 1, 3, 5 (DFM, n=18). Survival analysis and prognostic factors were evaluated by Kaplan-Meier method and Cox regression analysis.. All 98 patients were assessable for response and toxicity. There were 13 complete response, 36 partial response, 45 no changes and 4 progressive disease with a total response rate of 46.86%. The response rates of DLF, CLF and DFM regimens were 60.42%,46.86% and 27.78%, respectively (DLF vs DFM, P=0.027). The major side effects were nausea-vomiting, alopecia, bone marrow suppression and mucositis, and the others were uncommon. All side effects were tolerable and mild except for nausea-vomiting. Nausea-vomiting was mildest in CLF among the three regimens. After a median follow-up of 9 months, the overall median survival was 9 months (95% CI, 6.67 to 11.33 months), the median survival of the patients treated with DLF, CLF or DFM regimen was 10, 9 and 7 months, respectively (P=0.7402). Better prognosis was correlated with good conditions of patients before chemotherapy (KPS> or =80, P=0.000) and metastasis to lymph node, parenchyma or bone in stead of visceral organs (P=0.026). There was no correlation between the prognosis and age, sex, types of pathology and the regimen of therapy.. The DLF regimen is tolerable and more effective, thus could be recommended as a front-line standard treatment for advanced esophageal carcinoma. The CLF regimen is more suitable for feeble and older patients since it has the mildest side effects. The prognostic factors of advanced esophageal carcinoma include conditions before chemotherapy and the location of metastasis.

Topics: Adenocarcinoma; Adult; Aged; Alopecia; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carboplatin; Carcinoma, Squamous Cell; Cisplatin; Esophageal Neoplasms; Female; Fluorouracil; Follow-Up Studies; Humans; Infusions, Intravenous; Leucovorin; Leukopenia; Lymphatic Metastasis; Male; Middle Aged; Nausea; Neoplasm Staging; Proportional Hazards Models; Remission Induction; Survival Rate

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

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

The present study was conducted to evaluate the efficacy and safety of the combination of Oxaliplatin, Leucovorin and 5-FU as second line therapy, following relapse to Gemcitabine, in patients with advanced adenocarcinoma of the pancreas.. Patients with advanced pancreatic cancer previously treated with Gemcitabine were included in the study. All patients had histologically or cytologically confirmed adenocarcinoma of the pancreas that was unresectable, locally advanced or metastatic. Treatment consisted of Oxaliplatin 50 mg/m(2) (2-hour iv infusion), followed by Leucovorin 50 mg/m(2) (i.v. bolus) and 500 mg/m(2) 5-FU (1-hour iv infusion), administered weekly, until unacceptable toxicity or disease progression. Objective tumour response and toxicity were evaluated according to World Health Organisation (WHO) criteria.. A total of 30 patients, 20 men and 10 women, median age 63 years (range 52-71 years) and Karnofsky Performance Status (PS) of > or =50 entered the study. The majority of patients (96%) had locally advanced disease. A total of 380 doses of chemotherapy were delivered, a median of 12 doses per patient. Partial responses were observed in 7 patients (PR 23.3%), stable disease in 9 (SD 30.0%), while 14 patients progressed (PD 46.7%). Improved PS was observed in 18 (42.8%) patients. Patients that had responded to first-line Gemcitabine treatment were found more likely to respond or stabilize their disease with second-line treatment. The median duration of response was 22 weeks, and median overall survival was 25 weeks, Grade 3/4 toxicity expressed per chemotherapy dose included leukopenia 16%, anemia 3.2%, thrombocytopenia 3.2%, diarrhea 14.2%, fatigue 16.1% and neurotoxicity 4.2%. Eight patients (27%) suffered a febrile neutropenic event managed successfully with oral antibiotic home therapy, while 17 patients required G-CSF support. There were no treatment related deaths.. The combination of Oxaliplatin, Leucovorin and 5-FU was tolerated with manageable toxicity, offering encouraging activity as second-line treatment of patients with advanced or metastatic pancreatic adenocarcinoma, previously treated with Gemcitabine. Additional studies are warranted with this regimen in Gemcitabine relapsed pancreatic cancer patients.

Topics: Adenocarcinoma; Aged; Anemia; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Female; Fluorouracil; Gemcitabine; Humans; Infusions, Intravenous; Injections, Intravenous; Leucovorin; Leukopenia; Lymphatic Metastasis; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Pancreatic Neoplasms; Prognosis; Salvage Therapy; Survival Analysis; Thrombocytopenia

Standard chemotherapy for advanced gastric cancer remains undefined. Phase II trials show that taxol is effective in treating advanced gastric cancer. This multi-center prospective open randomized controlled study was to compare the efficacy of Taxol plus calcium folinate (CF)/5-fluorouracil (5-FU), Taxol plus oxaliplatin (OXA), and CF/5-FU plus cisplatin (DDP) on advanced gastric cancer, and analyze their toxicities.. Patients with measurable unresectable and/or metastatic gastric carcinoma were randomized into CF/5-FU+DDP (control), CF/5-FU + Taxol, and Taxol + OXA groups, and received up to 8 cycles of chemotherapy. Treatment efficacy and adverse events were evaluated according to WHO criteria.. A total of 180 patients were enrolled from May 2002 to May 2004, and randomized into the 3 groups; each group contained 60 patients. Of the 180 patients, 14 received 2 cycles of chemotherapy, 49 received 4 cycles, and 103 received 8 cycles. Treatment outcomes of 166 cases were evaluable. The response rate (RR) of naive patients or the patients with retroperitoneal lymph node metastasis was significantly higher in CF/5-FU+Taxol and Taxol+OXA groups than in control group (50.00% and 80.00% vs. 20.75%, P<0.05; 65.96% and 85.71% vs. 36.36%, P<0.05). But the RR of the patients with liver metastasis was similar among the 3 groups (28.57% and 39.13% vs. 34.62%, P>0.05). The occurrence rates of nausea/vomiting, anepithymia, stomatitis, and kidney damage were lower in study groups than in control group, but the occurrence rates of myelosuppression and peripheral nerve damage were higher in study groups than in control group. Allergic response occurred in 7 (5.88%) patients in study group, and 3 (2.52%) of them were serious. There was no treatment-related death.. Despite its hematotoxicity, the treatment efficacy of Taxol-based combination regimens on advanced gastric cancer is better than that of CF/5-FU + DDP regimen with tolerable toxicities. We recommend Taxol-based combination regimens as first-line regimens for advanced gastric cancer.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Paclitaxel; Prospective Studies; Remission Induction; Stomach Neoplasms; Thrombocytopenia

To evaluate the toxicity and efficacy of concurrent chemoirradiation with cisplatin followed by adjuvant ifosfamide, 5-fluorouracil and leucovorin in patients with stage IVb nasopharyngeal carcinoma (NPC) PATIENTS AND METHODS: Between October 1998 and August 2001, 35 Chinese patients with stage IVb NPC (N3a:12, N3b:23) were treated with by concurrent chemoirradiation using cisplatin 100 mg/m2 on days 1, 22, and 43 of radiotherapy, followed by adjuvant chemotherapy with 1.4 g/m2, ifosfamide, 450 mg/m2 5-fluorouracil, and 20 mg/m2 leucovorin daily for 5 days and repeated every 3 weeks for three cycles. Radiotherapy was given using standard fractionation at 2 Gy/day to a total of 68 Gy to the nasopharynx and 66 Gy to the neck.. All patients completed the prescribed radiotherapy. Twenty-three patients (66%) completed all scheduled cycles of chemotherapy. The compliance rate for concurrent and adjuvant chemotherapy was 71% and 80%, respectively. Grade 3 mucositis occurred in 37%, and grade 3 dermatitis occurred in 11.5% during radiotherapy. Grade 3 neutropenia occurred in 17% during concurrent chemotherapy, and grade 3-4 neutropenia occurred in 48.5% during adjuvant chemotherapy. There were no treatment-related deaths. With a median follow-up of 31 months, the 3-year relapse-free rate was 60%, and the 3-year overall survival rate was 74%. Locoregional control was excellent, with a 3-year local and nodal relapse-free rate of 91% and 83%, respectively. Eleven patients (31%) had developed distant metastases, and the 3-year distant metastasis-free rate was 66%.. The chemotherapy regimen tested is practical with an acceptable compliance rate. Despite having a more advanced stage disease, the observed outcome of our patients seems to be comparable with other series using platinum-based adjuvant chemotherapy. Further investigation to confirm the benefit of using the study regimen in advanced stage NPC is warranted.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Dermatitis; Female; Fluorouracil; Humans; Ifosfamide; Leucovorin; Leukopenia; Male; Middle Aged; Nasopharyngeal Neoplasms; Survival Rate; Vomiting

The aim of the present study was to evaluate the role of a weekly preoperative chemotherapy in locally advanced, unresectable gastric cancer. In all, 82 patients with an Eastern Oncology Cooperative Group PS

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease-Free Survival; Drug Administration Schedule; Epirubicin; Female; Filgrastim; Fluorouracil; Glutathione; Granulocyte Colony-Stimulating Factor; Humans; Leucovorin; Leukopenia; Levoleucovorin; Male; Middle Aged; Neoadjuvant Therapy; Recombinant Proteins; Stomach Neoplasms; Thrombocytopenia; Treatment Outcome

To evaluate the efficacy and safety profile of oral tegafur-uracil (tegafur combined with uracil in a molar of 1:4 ratio) plus leucovorin (LV) in patients with advanced biliary tract carcinoma (BTC).. Sixteen chemotherapy-naïve patients (nine males and seven females with a median age of 58.0 years) with BTC were prospectively enrolled in this study. The dose of tegafur-uracil (UFUR; TTY Biopharm Co. Ltd, Taipei, Taiwan) was 300 mg/m(2)/d (according to the dose of tegafur) and LV was 60 mg/day on day 1-28, followed by a 1-week break. The site of primary tumor included 10 intrahepatic cholangiocarcinomas (CC), one perihilar CC, four gallbladder cancers and one periampullar cancer. Fourteen patients were evaluated for tumor response.. No objective complete or partial responses were observed. Two patients had stable disease and 12 patients had disease progression. The median time to progression was 68 days (8-159 days) and the median survival time was 155 days (69-570 days). Sixteen patients were evaluable for toxicity. Grade III/IV toxicities were found in two patients only; one patient had grade III thrombocytopenia and one patient stopped therapy early due to grade IV diarrhea.. Oral tegafur-uracil plus LV is well tolerated but ineffective in patients with advanced BTC.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biliary Tract Neoplasms; Drug Administration Schedule; Female; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Survival Analysis; Tegafur; Thrombocytopenia; Uracil

The FLEP regimen (5-FU, LV, ETP, and CDDP) has been recommended as a combination chemotherapy to control advanced and recurrent gastric cancer. We performed a phase II study of this regimen in 49 patients with advanced gastric cancer.. The treatment regimen consisted of: 5-FU at 370 mg/m(2) (days 1-5, i.v. 24 h); LV at a dose of 30 mg (days 1-5, i.v. bolus); and ETP and CDDP each at 70 mg/m(2) (days 7 and 21, i.a. 2 h), which was repeated every five weeks.. The overall response rate was 40.8% (20/49 patients) and the median survival time was 12.6 months (range 1.1-41.8). The adverse events were Grade 3/4 leukocytopenia (16.3%), Grade 3/4 thrombocytopenia (8.2%), Grade 3 nausea and/or vomiting (4.1%), and Grade 3 stomatitis (2.0%).. Based on the encouraging response rate and prognosis, we recommend applying the FLEP regimen to patients with primary advanced gastric cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Stomach Neoplasms; Survival Rate

We investigated the activity of irinotecan given with a more convenient modified bimonthly de Gramont regimen of bolus and infusional 5-fluorouracil [IrMdG] in advanced or metastatic colorectal cancer in the first and second line setting. Irinotecan 180 mg m(-2) was infused over 90 min. L-folinic acid 175 mg or d,l folinic acid 350 mg was given over 2 h followed by a bolus of 5-fluorouracil (400 mg m(-2)) and a 46 h continuous infusion of 5-fluorouracil (2.4-2.8 g m(-2)). Forty-six previously untreated patients (Group A) and 36 who had received 5-fluorouracil for metastatic disease (Group B) were recruited. Seventy-eight patients were evaluable for response. A partial response was seen in 13 out of 43 (30% [95%CI 28.1-31.9%]) in Group A and 8/35 (23% [95% CI 17.9-28.1%]) in Group B. 40% (95%CI 38.1-41.9%) of Group A and 26% (95% CI 20.9-31.1%) of Group B patients achieved disease stabilisation. The median progression free survival from the start of this treatment was 7 months (95% CI 4.4-9.6 months) in Group A and 5 months (95% CI 2.8-7.2 months) in Group B. Median overall survival was 14 months (95% CI 9.0-18.9) in Group A and 11 months (95% CI 5.9-16.1) in Group B. Grade 3-4 toxicity in both treatment groups were similar; leucopenia 17% and diarrhoea 7-8%. Grade 3-4 mucositis was not seen and severe alopecia affected only three patients. IrMdG is an active and well-tolerated regimen for both the first and second line treatment of advanced colorectal cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Diarrhea; Disease-Free Survival; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Injections, Intravenous; Irinotecan; Leucovorin; Leukopenia; Male; Middle Aged; Mouth Mucosa; Neoplasm Metastasis; Stomatitis; Treatment Outcome

Biochemical modulation of 5-fluorouracil (5-FU) has been verified the evidence of significant improvement of survival and quality of life in patients with advanced colorectal carcinoma. We investigated the therapeutic and adverse drug reaction of intensive chemotherapy using cisplatin (CDDP), 5-FU and dl-leucovorin (LV) (PFL-therapy), which may be producing dual biochemical modulation effect of 5-FU for advanced colorectal carcinoma. Administration schedule was 13 mg/m2 of CDDP, 300 mg/m2 of 5-FU, and 30 mg/body of dl-LV for 5 consecutive days. This regimen was repeated at 3-week intervals in hospital. Sixteen patients were enrolled in this study, most of whom had a history of previous chemotherapy as adjuvant treatment, and the response rate was 25%, with four patients having "partial response" and eight "no change". In respect to performance status, 46% of patients who completed the protocol were markedly improved in spite of their poor performance status before treatment. Moreover, when patients were classified into two groups based on changes of the serum level of CEA, "responder in CEA level" showed better prognosis than "non-responder in CEA level". Major toxicities were nausea, hyperglycemia and neutropenia. Three patients experienced Grade 4 hematological side effect, but these complications resolved quickly in all patients except for one patient. PFL-therapy is effective for advanced colorectal cancer with large tumor burden and showed the same prognostic result as the American and European trials in spite of smaller number of treatment cycles and a history of previous chemotherapy. We will be able to demonstrate the usefulness of this regimen for Japanese patients with advanced colorectal cancers after adding new cases to the present report.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoembryonic Antigen; Cisplatin; Colorectal Neoplasms; Diarrhea; Drug Administration Schedule; Female; Fluorouracil; Humans; Karnofsky Performance Status; Leucovorin; Leukopenia; Male; Middle Aged; Nausea; Skin Diseases; Stomatitis; Survival Rate; Thrombocytopenia; Treatment Outcome; Vomiting

In an open prospective study with matched historical controls we aimed to evaluate whether a polysaccharide fraction isolated from the herb Echinacea purpurea could counteract the undesired effects of chemotherapy. Fifteen patients with advanced gastric cancer undergoing palliative chemotherapy with etoposide, leucovorin and 5-fluorouracil (ELF) received for 10 days (beginning 3 days before chemotherapy) daily i.v. injections of 2 mg of a polysaccharide fraction isolated from Echinacea purpurea herb cell cultures (EPS-EPO VIIa). The median number of leukocytes 14-16 days after chemotherapy was 3630/microL (range 1470-5770) in the patients receiving EPS-EPO VIIa compared with 2370/microL (870-3950) in the patients of the historical control group (p = 0.015). EPS-EPO VIIa had no clinically relevant effects on phagocytic activity of granulocytes or on lymphocyte subpopulations. Sixty-eight adverse events including two deaths were observed, most likely due to chemotherapy and the general condition of the patients. However, an association with the test intervention cannot be ruled out completely. The results of this pilot study suggest that EPS-EPO VIIa might be effective in reducing chemotherapy-induced leukopenia. The efficacy and safety should be investigated in further studies.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cells, Cultured; Echinacea; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Leukocyte Count; Leukopenia; Lymphocytes; Male; Middle Aged; Phytotherapy; Pilot Projects; Plant Extracts; Polysaccharides; Stomach Neoplasms; Treatment Outcome

Chemotherapy of neuroendocrine tumors must be improved. The most widely used regimen, which combines streptozotocin with fluorouracil, commonly obtains poor results. The best response rate that has been reported for carcinoid tumors is 33%. From July 1991 through September 1994, 18 patients who had advanced neuroendocrine tumors-including nine carcinoid tumors, seven neuroendocrine tumors of unknown primary site, one insulinoma, and one paraganglioma-were treated with a regimen of dacarbazine, 400 mg/m2/day, plus fluorouracil, 1 g/m2/day, with leucovorin, 200 mg/m2/day, for 2 days every 21 days (DTIC-LVFU2 protocol). The results were assessed according to the World Health Organization criteria of toxicity and response. Toxicity was moderate. The most severe side effects were grade 3 vomiting in two patients, grade 3 leukopenia in three patients, and grade 3 mucositis in one patient. The overall response rate was 27%, with only one partial response for carcinoid tumors but one complete and three partial responses for the other tumor types. Efficacy was insufficient in patients who had carcinoid tumors but the combination of dacarbazine with fluorouracil and leucovorin could be an effective regimen for the treatment of neuroendocrine tumors of unknown primary site.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoid Tumor; Dacarbazine; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Nausea; Neoplasms, Unknown Primary; Neuroendocrine Tumors; Survival Rate

Patients with advanced gastric cancer unresponsive or progressing after PELF chemotherapy (5-fluorouracil, leucovorin, cisplatin and epidoxorubicin) received paclitaxel at the dose of 225 mg/m2 every 3 weeks, over 3 h infusion. Thirty-six patients entered the study, and all of them were evaluable for response and toxicity. Toxicity was mild: apart from alopecia, grade 3 toxicities were leukopenia and thrombocytopenia in six patients, and grade 2 neurotoxicity in seven patients. Eight patients (22.2%, 95% CI: 9-35%) achieved an objective response, with a median duration of 5 months. Median survival time for all patients was 8 months. In 16 of 36 patients (44%), treatment determined a significant relief of symptoms. Out-patient paclitaxel given over 3 h may be effective as salvage treatment in patients with advanced gastric cancer refractory to first line chemotherapy.

Topics: Adult; Aged; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Epirubicin; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Paclitaxel; Stomach Neoplasms; Survival Analysis; Thrombocytopenia; Time Factors

The efficacy of the treatment of advanced gastric cancer is not very good. The response rate to the original etoposide--leucovorin--5-fluorouracil (ELF) treatment is 53% with tolerable side effects. Whether increasing the dose intensity by prolonging the duration of infusion with 5-fluorouracil (5-FU) and leucovorin (LV) from 3 to 5 days for advanced or metastatic gastric cancer patients would enhance the efficacy but not increase side effects is still unknown.. Thirty-six advanced or metastatic gastric cancer and chemotherapy-naïve patients with measurable or evaluable diseases were scheduled to receive intravenous etoposide 100 mg/m2/day on days 2-4, LV 300 mg/m2/day intravenously and 5-FU 500 mg/m2/day intravenously on days 1-5, every 4 weeks. All patients who received at least two courses of chemotherapy were evaluated for tumor response, survival and response duration and toxicity according to the WHO criteria.. Thirteen patients showed a response, including five with complete response (CR). The overall response rate was 36% (95% confidence interval, CI, 20-52%) in the whole group and 46% (95% CI 28-66%) in the 28 patients with measurable disease. The median progression-free interval and overall median survival time were 5 and 7 months, respectively. The most frequent toxicity was alopecia (grade I/II 56.3%). The incidence of grade III or greater myelosuppression was 5.9%. No treatment-related death occurred.. The efficacy of the modified ELF by increasing the dosages of 5-FU and LV is not superior to the results of the original regimen, yet it is a relatively safe and tolerable combination regimen for advanced gastric cancer.

Topics: Adult; Aged; Alopecia; Anemia; Antineoplastic Combined Chemotherapy Protocols; Diarrhea; Drug Administration Schedule; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Levoleucovorin; Male; Middle Aged; Prognosis; Stomach Neoplasms; Survival Analysis

A combination of oral 13-cis-retinoic acid (cis-RA) and subcutaneous interferon alfa-2a (IFN) has been reported to yield high response rates in patients with squamous cell carcinomas (SCCAs) of the cervix and skin. Cisplatin and 5-fluorouracil with leucovorin (5-FU/LV) are chemotherapeutic agents commonly used for SCCAs.. To determine the maximum tolerated doses (MTDs) of cisplatin and 5-FU/LV when combined with IFN and cis-RA, and to define a recommended phase II regimen for testing in cervical cancer and other appropriate tumor types.. Phase I cohort design. Cisplatin was administered every 3 weeks. 5-FU and LV were administered together as a weekly 24-h infusion. Cis-RA was given orally twice daily. IFN was initially given subcutaneously at a dose of 3 million units (MU) daily.. A total of 31 patients were treated. The IFN dose was reduced to 3 MU three times weekly because of patient intolerance. Cytopenias prevented the administration of weekly 5-FU/LV. Single-agent cisplatin with three times weekly IFN and twice daily cis-RA was tolerable. Four partial responses were observed, in patients with adrenal cancer, bladder cancer, gastric cancer, and adenocarcinoma of unknown primary.. The recommended phase II regimen is cisplatin 100 mg/m2 every 3 weeks, IFN 3 MU three times weekly, and cis-RA 1 mg/kg daily. This appears to be more toxic than single-agent cisplatin, but the preliminary activity observed warrants further testing.

Topics: Administration, Oral; Adult; Aged; Antidotes; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Synergism; Female; Fluorouracil; Humans; Injections, Subcutaneous; Interferon alpha-2; Interferon-alpha; Isotretinoin; Leucovorin; Leukopenia; Male; Middle Aged; Neoplasms; Recombinant Proteins; Remission Induction

To compare the efficacy and toxicity of fluorouracil (FU) and racemic leucovorin (d,l-LV) versus FU combined with the l-isomer of leucovorin (l-LV) in the treatment of advanced colorectal cancer.. A total of 248 patients with advanced measurable colorectal cancer previously unexposed to chemotherapy were randomly assigned to treatment with either FU (400 mg/m2/d by intravenous [I.V.] infusion for 2 hours) and racemic LV (100 mg/m2/d by I.V. bolus injection) given for 5 consecutive days, or the combination of FU and the pure l-isomer of LV using the same dose schedule. In both treatment arms, courses were administered every 28 days if toxicity allowed for a total of 6 months, unless evidence of tumor progression was documented earlier.. There were no significant differences between the FU/racemic LV and the FU/l-LV arm in the overall response rate (25% v 32%), duration of response (7.2 v 8.0 months), median time to progression or death (6.25 v 8.0 months), or median overall survival time (14.5 v 15.0 months). Except for minor myeloid toxic effects associated with FU/l-LV, there was also no significant difference in terms of adverse reactions. Gastrointestinal symptoms, specifically mucasitis and diarrhea, were less frequent and less severe in both treatment arms compared with other trials with FU/racemic LV reported in the literature, which might be because of the prolonged administration of FU used in both arms.. The combination of FU/l-LV produced response rates, response durations, and survival times similar to those with FU/d,l-LV. Biochemical modulation of FU by either pure l-LV or racemic LV thus appears to result in equivalent clinical efficacy.

Topics: Adult; Aged; Agranulocytosis; Antidotes; Antimetabolites, Antineoplastic; Colorectal Neoplasms; Disease Progression; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Neoplasm Staging; Stereoisomerism; Survival Analysis

Based on reports of substantial antitumor efficacy of the combination of mitoxantrone (DHAD), 5-fluorouracil (FU) and leucovorin (LV), a clinical trial was performed to attempt augmentation of the dose of DHAD with filgrastim support. The doses and schedules, all intravenous, were DHAD (total dose divided over days 1 and 2), level I, 16 mg/m2; II, 20 mg/m2; III, 24 mg/m2; IV, 32 mg/m2; and LV, 300 mg, followed by FU, 350 mg/m2, on days 1-3. Filgrastim was given at 5 micrograms/kg/day subcutaneously on days 4-13. The planned cycle length was 21 days. Three or 4 patients were to be entered at each dose level and the maximum tolerated dose (MTD) was defined as the dose immediately below that which resulted in 2 patients with dose-limiting toxicity (DLT) in cycle 1. Once an apparent MTD was identified, an additional 6 patients were to be entered. Twenty patients (pts) were entered: level I: 3 pts; II: 3 pts; III: 10 pts: IV: 4 pts. The major toxicity was found to be cumulative thrombocytopenia with platelet counts < or = 20,000/microL occurring after cycle 1 at all levels beyond level I and five pts (25%) were removed from treatment solely because of platelet toxicity. Additional serious toxicities included grade 4 stomatitis in one patient (level IV) and cardiac toxicity in 2 patients with prior doxorubicin exposure. Ten pts had measurable and 8 had evaluable disease, and in 17 pts assessed, 5 (29%) achieved an objective response. The response rates in this study are lower than reported in the literature for the combination of DHAD, 5FU, LV and this may be related to the fact that only 40% of the patients were removed from protocol treatment because of disease progression. On the basis of limited DHAD-dose augmentation, toxicities observed, and modest response rate, the filgrastim-supported DHAD, 5FU, LV regimen as utilized in this study cannot be recommended for further development for treatment of women with metastatic breast cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Filgrastim; Fluorouracil; Granulocyte Colony-Stimulating Factor; Humans; Leucovorin; Leukopenia; Middle Aged; Mitoxantrone; Neoplasm Metastasis; Patient Selection; Platelet Count; Recombinant Proteins; Survival Rate; Thrombocytopenia; Time Factors

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

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

The oral fluoropyrimidines have proved to be active in colorectal cancer in Japan and, recently, in the United States and Europe. Continuous oral administration simulates protracted fluorouracil (5-FU) continuous intravenous infusion. The purpose of this trial was to evaluate the tolerability and potential advantages of oral treatment for colorectal cancer in the elderly. The main inclusion criterion was age over 72 years. Patients were treated with UFT (tegafur plus uracil) 400 mg/24 hours (fixed doses) continuously plus folinic acid 45 mg/24 hours until toxicity. If grade 3 or 4 toxicity appeared, treatment was stopped until recovery. From September 1994 to November 1996, 126 patients were included. For the analysis in November 1996, 77 patients were evaluable for response, toxicity, and survival. The patients, including 34 women and 43 men, had a median age of 74 years (range, 72 to 82 years of age). The Karnofsky performance status was 60% to 80% for 41 patients and 90% to 100% for 36 patients. Liver metastasis was present in 48% of the cases, and 42% were locoregional and peritoneal. Toxicity was mild, with only one patient having grade 3 thrombocytopenia, 11 (14%) grade 3 or 4 nausea/vomiting, seven (9%) grade 3 or 4 diarrhea, and one grade 3 mucositis. Four patients (5%) had complete responses and nine (11.6%) partial responses, for an objective response rate of 16.9% (95% confidence interval, 9% to 27%). Twenty-two patients (28.6%) showed no change. The number of patients in whom disease did not progress (ie, patients with complete plus partial responses plus those with stable disease) was 35 (45.4%) (95% confidence interval, 34% to 57%). With a maximum follow-up of 24 months, the median actuarial survival is 14.4 months. The number without disease progression and the median survival in this preliminary analysis suggests that this schedule is a moderately effective, comfortable, treatment with only mild toxicity, that can be recommended for use in the elderly, and it warrants further study.

Topics: Aged; Aged, 80 and over; Antidotes; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Diarrhea; Drug Combinations; Drug Therapy, Combination; Female; Humans; Leucovorin; Leukopenia; Male; Nausea; Survival Analysis; Tegafur; Treatment Outcome; Uracil

Thirty-nine patients with locally advanced or metastatic gastric carcinoma received oral UFT (tegafur and uracil) plus leucovorin. Treatment consisted of UFT 360 mg/m2/day plus leucovorin 25 mg/m2/day, given orally in divided daily doses for 21 days followed by a 7-day rest period. The median age of the patients was 64 years, and the median World Health Organization performance status was 2. Patients received a median of two courses of treatment (range, 1 to 25). Among 37 evaluable patients, two patients achieved a complete response, and eight had partial responses, for an overall response rate of 27% (95% confidence interval, 15.4% to 42.9%). Stable disease was reported in 12 patients (32%) and another 15 showed disease progression. The median duration of response was 30 weeks, and the median duration of survival was also 30 weeks (range, 8 to 111). All patients were evaluable for toxicity. Significant toxicity (World Health Organization grade 3 or 4) included diarrhea in seven patients (18%), oral mucositis in six (15%), and nausea/vomiting in six patients. We conclude that oral UFT plus leucovorin, an outpatient regimen, has favorable activity in patients with gastric carcinoma and has tolerable toxicities.

Topics: Adult; Aged; Antidotes; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Diarrhea; Drug Combinations; Female; Follow-Up Studies; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Nausea; Stomach Neoplasms; Survival Rate; Tegafur; Treatment Outcome; Uracil

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 date there is no established chemotherapeutic treatment for patients with unresectable locally advanced and/or metastatic carcinomas of the exocrine pancreas or the gallbladder. A multicenter Phase II trial has been performed by the Southern Italy Oncology Group with the aim of evaluating the clinical effectiveness and tolerability of weekly 5-fluorouracil (5-FU) in modulation with intravenous (i.v.) high dose levofolinic acid and oral hydroxyurea.. A total of 70 patients fulfilling the standard eligibility for a Phase II study were enrolled in the trial. Forty patients had advanced pancreatic adenocarcinoma and 30 had advanced gallbladder carcinoma. The treatment schedule was: levofolinic acid, 100 mg/m2, in 500 mL of normal saline over 2-hour infusion followed by 5-FU, 600 mg/m2 i.v. bolus, and oral hydroxyurea, 1000 mg/m2, for 1 day every week for 6 consecutive weeks followed by 15 days of rest.. Among the 40 patients with pancreatic adenocarcinoma, 5 (12.5%; 95% confidence level [CL], 8.5-16.5%) showed a partial response with a median duration of 5.6+ months, and 13 had stable disease. Twenty-two patients progressed. Median survival was 5.8 months. Among patients with advanced gallbladder carcinoma, 9 of 30 had a partial response (30%; 95% CL, 26-34%) with a median duration of 6.5 months, and 8 (27%) had stabilization of disease. Thirteen patients showed progressive disease. Median overall survival was 8 months. Toxicity was mild, with Grade 1 to 2 leukopenia and gastrointestinal toxicity the most frequent side effects. No chemotherapy-related deaths were observed.. 5-FU in modulation with i.v. levofolinic acid and oral hydroxyurea on a weekly schedule is well tolerated by the vast majority of patients with locally advanced and/or metastatic carcinoma of the pancreas or the gallbladder. Although response rate and overall survival for patients with pancreatic adenocarcinoma are far from acceptable, the 30% overall response rate achieved in patients with advanced gallbladder carcinoma suggests that 5-FU in modulation with levofolinic acid and hydroxyurea is active in this neoplasm. The combination of modulated 5-FU with other antineoplastic drugs seems worthy of clinical testing in further controlled trials.

Topics: Adenocarcinoma; Administration, Oral; Aged; Antidotes; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Disease Progression; Drug Administration Schedule; Female; Fluorouracil; Gallbladder Neoplasms; Humans; Hydroxyurea; Infusions, Intravenous; Injections, Intravenous; Italy; Leucovorin; Leukopenia; Male; Middle Aged; Pancreatic Neoplasms; Remission Induction; Survival Rate

A phase I trial of 5-fluorouracil (5-FU), leucovorin (LV) and interferon (IFN) was conducted in 15 advanced colorectal cancer patients refractory to a bolus regimen of 5-FU/LV. Therapy consisted of a weekly i.v. infusion of 5-FU at 2600 mg/m2 administered concomitantly with LV at 500 mg/m2 over a 24 h period. IFN-alpha 2b was administered by 24 h infusion from the second cycle at escalating dose (4.5, 9, 18 and 27 MU/m2). The maximum tolerated dose of IFN was 18 MU/m2. At 27 MU/m2 two patients complained of diarrhea grade 3, so that the escalation of IFN dose was stopped. Two patients achieved a partial response (IFN level dose 9-18 MU/m2). Eight patients had stable disease. Pharmacokinetics of 5-FU were not influenced by IFN at any level dose. Our results show that doses of IFN of 18 MU/m2 given by a 24 h infusion can be administered safely to an established and active schedule of weekly 24 h infusion of 5-FU and LV. A phase II study has been planned to define the level of activity of this regimen.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Carcinoma; Colorectal Neoplasms; Diarrhea; Female; Fluorouracil; Humans; Interferon alpha-2; Interferon-alpha; Leucovorin; Leukopenia; Male; Middle Aged; Recombinant Proteins; Stomatitis

Dose intensification of 5-fluorouracil (5-FU) is complicated by increased toxicity. 5-FU is a fluorine-substituted pyrimidine analog of uracil. In preclinical studies, administration of oral uridine (Ur) has been shown to allow for dose intensification of 5-FU with enhancement of its antitumor activity. Therefore, a Phase I trial was designed aimed at dose intensification of 5-FU as a component of a modified 5-FU-doxorubicin-methotrexate (FAMTX) regimen using oral Ur rescue.. Methotrexate (MTX) was administered to all patients at a fixed dose of 1.5 g/m2. MTX was followed 24 hours later by escalating doses of 5-FU starting at 800 mg/m2 with leucovorin rescue. Cycles of 5-FU and MTX were repeated every 15 days. Every other cycle, patients received doxorubicin. "Adria cycles") at a dose of 30 mg/m2. Oral Ur was administered at a dose of 8 gm/m2 every 6 hours for 12 doses. In the first phase of the study, patients received Ur only if they developed Grade 3 or 4 hematologic toxicity. In the second phase, all patients received Ur 24 hours after 5-FU on all cycles.. Without Ur rescue, the maximum tolerated dose (MTD) of 5-FU was 900 mg/m2 on the Adria cycles and 1.1 gm/m2 on the non-Adria cycles. With Ur, the MTD of 5-FU increased to 1.2 gm/m2 on the Adria cycles and to 1.6 gm/m2 on the non-Adria cycles.. In this modified FAMTX regimen, oral Ur administration allowed for dose-intensification of 5-FU, with a 33% increase in the MTD of 5-FU on the Adria cycles and a 45% increase in the MTD of 5-FU dose on the non-Adria cycles.

Topics: Administration, Oral; Adult; Aged; Antidotes; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Male; Methotrexate; Middle Aged; Neoplasms; Neutropenia; Uridine

Thirty patients with recurrent primary brain tumors were treated with a combination of 5-fluorouracil and leucovorin. There were three responses seen. Toxicity consisted of stomatitis, diarrhea, and hematological suppression. 5-fluorouracil and leucovorin would appear to be minimally effective in recurrent brain tumors.

Topics: Adult; Aged; Antidotes; Antimetabolites, Antineoplastic; Astrocytoma; Brain Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Oligodendroglioma; Recurrence; Stomatitis; Thrombocytopenia

Background In a previous phase I to II trial, we have shown that the maximum tolerable dose (MTD) of 5-Fluorouracil (5-FU) in 48-hour continuous infusion (CI) weekly was 3.5 gr/m2. In a subsequent confirmative phase II trial with 85 evaluable patients, a 38.5% response rate was obtained and the median survival reached was 12 months. These data were comparable to those achieved by biochemical modulation of 5-FU with Leucovorin. On this basis we tried to modulate high-dose 5-FU (3 gr/m2) with oral leucovorin (LV) but the regimen was too toxic and the dose had to be reduced. A new phase II trial with 2 g/m2/week plus oral leucovorin was planned. Patients received a median dose intensity of 5-FU of 1.6 g/m2/week (range 0.9-2). Three complete responses and 36 partial responses were observed. Overall response rate was 37.5% (95% CI, 28% to 46.8%). Median time to progression has been 7.4 months, and median survival 14.4 months. WHO grade 3 diarrhea was seen in 27 patients (24.5%). Grade 3 mucositis was also seen in 9 (8.1%) patients, and grade 4 was observed in one. Grade 3 nausea and vomiting was reported in 13 (11.7%) patients. Grade 3 hand-foot syndrome was detected in only 5 (4.5%) patients. Grade 4 leukopenia was observed in 1 case and grade 3 to 4 thrombocytopenia was observed in two cases, respectively. Oral leucovorin modulation of weekly 48-hour continuous infusion of 5-FU at 2 g/m2 is an active regimen, with diarrhea and mucositis as main limiting toxicities. Its antitumor activity does not seem superior to that obtained with a weekly 48 hour continuous infusion of 5-FU alone at a dose of 3.5 g/m2.

Topics: Administration, Oral; Adult; Aged; Anemia; Antidotes; Antimetabolites, Antineoplastic; Carcinoma; Colorectal Neoplasms; Diarrhea; Dose-Response Relationship, Drug; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Leukopenia; Male; Middle Aged; Spain; Treatment Outcome; Vomiting

Bayesian methods for the analysis of clinical trials data have received increasing attention recently as they offer an approach for dealing with difficult problems that arise in practice. A major criticism of the Bayesian approach, however, has focused on the need to specify a single, often subjective, prior distribution for the parameters of interest. In an attempt to address this criticism, we describe methods for assessing the robustness of the posterior distribution to the specification of the prior. The robust Bayesian approach to data analysis replaces the prior distribution with a class of prior distributions and investigates how the inferences might change as the prior varies over this class. The purpose of this paper is to illustrate the application of robust Bayesian methods to the analysis of clinical trials data. Using two examples of clinical trials taken from the literature, we illustrate how to use these methods to help a data monitoring committee decide whether or not to stop a trial early.

Topics: Bayes Theorem; Clinical Trials as Topic; Data Collection; Data Interpretation, Statistical; Extracorporeal Membrane Oxygenation; Fluorouracil; Granulocyte Colony-Stimulating Factor; Humans; Infant, Newborn; Leucovorin; Leukopenia; Likelihood Functions; Neoplasms; Persistent Fetal Circulation Syndrome; Stomatitis; Survival Rate; Treatment Outcome

We report the results of a multicenter clinical trial comparing three combination chemotherapeutic regimens including 5-fluorouracil (5-FU) and l-leucovorin (l-LV). One hundred and twenty-two patients were randomized to three regimens comprising 5-FU (600 mg/m2) plus high-dose l-LV (250 mg/m2) in six doses given weekly by i.v. injection midway during a 2-hr infusion of l-LV (regimen A), 5-FU (370 mg/m2) plus high-dose l-LV (100 mg/m2) given simultaneously for 5 consecutive days and a 23-day interval between treatments (regimen B) and 5-FU (370 mg/m2) plus low-dose l-LV (10 mg/m2) with the same dose administration schedule as regimen B (regimen C). The response rates were 32.4% (12/37 cases) in Regimen A, 20.0% (8/40) in regimen B and 11.1% (4/36) in regimen C. The most prominent side effects observed in regimen A were diarrhea (53.8%) and leukopenia (53.8%); however, they were within permissible levels. The combinations of high-dose l-LV and 5-FU (regimen A and B) had higher response rates than that of low dose l-LV and 5-FU (regimen C). Weekly administration of high-dose l-LV and 5-FU (regimen A) is now being expanded to late phase II trials.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Diarrhea; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Leukopenia; Male; Middle Aged; Survival Rate

A multicenter cooperative study was conducted to evaluate the clinical efficacy of l-leucovorin (l-LV) and 5-fluorouracil (5-FU) treatment in 69 cases of advanced gastric cancer. l-LV was administered intravenously by a 2-hour infusion at a dosage of 250 mg/m2 and 5-FU at a dosage of 600 mg/m2, intravenously via bolus one hour after administration of l-LV had been started. The combination was given weekly for 6 weeks followed by a 2-week rest period. Patients were evaluated for response after the sixth dose. Nineteen PRs were noted in the 55 patients for an overall response rate of 34.5%. Median survival time was 190 days for eligible cases, and 448 days for PR cases. Age and performance status (PS) appeared to influence clinical response. Patients aged 49 years or younger showed a significantly higher PR rate than those aged 50 years or older. The PR rate was significantly higher in the patients of PS 0-1 than those of PS 2. Diarrhea and leukopenia were experienced in 46.7% and 65% of patients, respectively. Patients who had severe toxicities required discontinuity of treatment. After recovery, treatment was repeated. The clinical results are promising for patients with advanced gastric cancer, particularly middle-aged patients. However, whether the l-leucovorin and 5-FU combination therapy will ultimately produce superior results in middle-aged patients awaits the results of Phase III trials.

Topics: Adult; Aged; Diarrhea; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Injections, Intravenous; Leucovorin; Leukopenia; Male; Middle Aged; Remission Induction; Stomach Neoplasms; Survival Rate

A multicentral cooperative study was conducted to evaluate the clinical efficacy and toxicity of l-Leucovorin (l-LV) and 5-fluorouracil (5-FU) in advanced colorectal cancer. The administration schedule was a two-hour intravenous infusion of l-LV (250 mg/m2) and an intravenous bolus injection of 5-FU (600 mg/m2), given one hour after the beginning of the l-LV infusion. Sixty-four patients were treated weekly for six weeks followed by two-weeks rest, and then evaluated for response. Complete response and partial response were obtained in 21 patients (32.8%). The median survival time was 12.8 months. The most prominent side effects were anorexia (57.8%), nausea and vomiting (56.3%), diarrhea (48.4%) and myelosuppression such as leucopenia (54.7%), thrombocytopenia (18.8%) and decreased hemoglobin (40.6%). These side effects, however, were within permissible levels. Severe toxicity was prevented by discontinuance of the treatment. From the present study, l-LV and 5-FU combination therapy seems to be a very promising and useful treatment for patients with advanced colorectal carcinoma.

Topics: Adult; Aged; Anorexia; Colorectal Neoplasms; Diarrhea; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Injections, Intravenous; Leucovorin; Leukopenia; Male; Middle Aged; Nausea; Remission Induction; Survival Rate

Cancer is most common in older age groups, but little information is available with regard to the impact of age on chemotherapy toxicity. This study was undertaken to determine if age is an independent risk factor for 5-fluorouracil (5-FU) toxicity.. Toxicity data from a prospective, randomized, multiinstitution trial of 5-FU-based treatment for advanced colorectal cancer were analyzed. Toxicity for each organ system was graded. Individual organ toxicity proportions were compared using chi-square analysis. A logistic regression was performed using age (younger than 70 years vs. 70 years or older), sex, treatment arm, performance status, and length of therapy as model parameters to predict severe toxicity. Toxicity in 331 patients was analyzed.. Advanced age was significantly associated with the occurrence of any severe toxicity (58 vs. 36%, P < 0.001), leukopenia (24 vs. 10%, P < 0.005), diarrhea (24 vs. 14%, P = 0.01), vomiting (15 vs. 5%, P = 0.01), severe toxicity in more than 2 organ systems (10 vs. 3%, P = 0.02), and treatment mortality (9 vs. 2%, P = 0.01). By univariate analysis, age (P < 0.001) and sex (P < 0.0001) were independent predictors of severe toxicity. Twenty-two of 27 women age 70 years or older had severe toxicity.. Age 70 years or older and sex are risk factors for severe toxicity from 5-FU-based chemotherapy. Advanced age does not contraindicate the use of this type of chemotherapy, but close monitoring for multiple organ toxicities and vigorous supportive care of those with toxicity are required. Dosing decisions in older patients are difficult and must integrate assessments of organ function, comorbidities, overall physical status, and goals of treatment, in an effort to ensure the best possible outcome for these patients.

Topics: Age Factors; Aged; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Diarrhea; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Risk Factors; Sex Factors; Vomiting

'Tomudex' (ZD1694), a direct and specific thymidylate synthase (TS) inhibitor entered phase III studies in November 1993. We present here the first analysis of a randomised multicentre, international phase III study. 439 patients with previously untreated advanced colorectal cancer were randomised to Tomudex 3.0 mg/m2 given once every 3 weeks or 5-fluorouracil (5-FU) 425 mg/m2 and leucovorin (LV) 20 mg/m2 for 5 days (the Mayo regimen), given every 4-5 weeks. Patients were evaluated weekly for toxicity and every 12 weeks for objective response. The two groups were well matched in terms of demographic characteristics. The mean age of the patients was 61 years and most had either liver (78%) or lung (25-29%) metastases. Ninety seven per cent of patients allocated to Tomudex and 94% of those allocated to 5-FU plus LV had measurable disease. Response was assessed using WHO/UICC criteria; all response data were source validated; 19.8% of patients who received Tomudex and 12.7% of patients who received 5-FU plus LV had complete or partial responses (P = 0.059, odds ratio 1.7, 95% confidence limits 0.98-2.81). There were no statistically significant differences in time to progression or survival between the two groups. Patients who received Tomudex spent a substantially shorter time in hospital for dosing and had significantly lower rates of grade 3 and 4 toxicities such as leucopenia and mucositis. Patients who received Tomudex had a significantly higher incidence of reversible grade 3 or 4 increase in transaminases, which appear to be of limited clinical significance. Improvement in quality of life, weight gain and performance status was seen in both groups. Tomudex has benefits in terms of higher response rates, reduced toxicity and more frequent palliative benefits when compared with 5-FU plus LV in the management of advanced colorectal cancer, and has a more convenient administration schedule.

Topics: Adult; Aged; Aged, 80 and over; Antidotes; Antimetabolites, Antineoplastic; Colorectal Neoplasms; Drug Therapy, Combination; Female; Fluorouracil; Follow-Up Studies; Humans; Length of Stay; Leucovorin; Leukopenia; Male; Middle Aged; Quality of Life; Quinazolines; Stomatitis; Survival Rate; Thiophenes

Thirty patients with measurable metastatic breast carcinoma were treated with a combination of cyclophosphamide 600 mg/m2 on day 1, levofolinic acid 100 mg/m2 plus 5-fluorouracil 375 mg/m2 on days 1-3, and epidoxorubicin (EDXR) in three refracted doses on days 1-3 with G-CSF rescue for 10 days. In the phase I part of the study, groups of 3 patients received EDXR 20, 25, 30, 35, and 40 mg/m2/day until the dose limiting toxicity (DLT) was reached. At the dose of 40 mg/m2/day prolonged grade 4 leukopenia, severe proctitis, and grade 3 diarrhea represented the DLT. All subsequent patients were treated at the maximal tolerated dose of EDXR (35 mg/m2/day). In the group of 18 patients treated at 35 mg/m2/day the overall response rate was 78%, with 22% CR and 56% PR. Four patients did not respond. Objective responses were seen at all tumor sites including bone and viscera, which usually are rather chemotherapy insensitive. Toxicity was generally acceptable. Although the response rate was quite high, the duration of objective tumor regression and patients' survival were not impressive. In conclusion, we do not recommend routine use of such an aggressive regimen for palliation of advanced breast cancer. Results of the present and similar studies may, however, be useful for planning of neoadjuvant or adjuvant trials with curative intent.

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoma; Cyclophosphamide; Drug Administration Schedule; Epirubicin; Female; Fluorouracil; Granulocyte Colony-Stimulating Factor; Humans; Leucovorin; Leukopenia; Middle Aged; Recombinant Proteins; Treatment Outcome

Based upon prior data suggesting that alpha-interferon possesses chemomodulatory activity, a pilot study was conducted in which patients with advanced colorectal carcinoma were treated with 5-fluorouracil (5-FU), leucovorin (LV) and Roferon-A. Treatment consisted of LV 20 mg/m2 i.v. push followed by 5-FU, 425 mg/m2 i.v. push daily for 5 days every 4 weeks for 2 cycles, then every 5 weeks; Roferon-A 9 million units subcutaneously was given three times weekly every week. Forty-six eligible patients with bidimensionally measurable disease who had received no prior chemotherapy for advanced disease were treated with this regimen. The most frequent toxicity was leukopenia with 80% of patients experiencing some degree of leukopenia and the most severe toxicity was granulocytopenia with 46% of patients experiencing granulocyte counts < 1,000/mm3. Among the 46 eligible patients, the objective response rate was 13% (95% confidence interval, 5-26%). Thirty-five of the 46 patients have died with a median survival of 17 months. This regimen has significant toxicity and insufficient activity against advanced colorectal carcinoma to warrant further trials.

Topics: Adult; Aged; Colorectal Neoplasms; Drug Therapy, Combination; Female; Fluorouracil; Humans; Interferon alpha-2; Interferon-alpha; Leucovorin; Leukocyte Count; Leukopenia; Male; Middle Aged; Recombinant Proteins

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

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

A total of 50 patients were treated weekly with 5-fluorouracil (FU), leucovorin (LV), and 4'-O-tetrahydropyranyl-doxorubicin (THP) as first-line chemotherapy for advanced breast cancer (ABC). In phase I the doses of LV (500 mg/m2, day 1) and FU (350 mg/m2, day 1) were held constant, while the dose of THP (day 1) was escalated, from the initial dose of 10 mg/m2 up to the maximum tolerated dose (MTD). Twenty-eight patients entered phase I, and MTD for THP was defined as 35 mg/m2 in this combination. Dose-limiting toxicities were myelosuppression and hepatotoxicity. In phase II, another 22 patients were treated with THP at a dose level of 30 mg/m2. Including 4 patients already treated at this dose in the first part, 25 patients were evaluable for response: 1 patient obtained a complete response (CR) and 13 showed a partial response (PR), giving an objective response rate of 56%. The median duration of response was 9.1+ months and median survival, 15.5+ months. Side effects were generally mild, with ECOG grade I and II leukopenia in 51% of all cycles and grade III in 3% of the courses. Other toxicity included nausea and vomiting (54% and 8%, respectively) and alopecia (24%), all restricted to ECOG grade I and II. Our results suggest that weekly THP/LV-FU represents an active regimen for first-line treatment of ABC with relative low toxicity.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Diarrhea; Doxorubicin; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Middle Aged; Nausea

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

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

38 patients with advanced oesophageal carcinoma were treated with intravenous (i.v.) folinic acid (300 mg/m2), 5-fluorouracil (500 mg/m2), etoposide (100 mg/m2), and cisplatin (30 mg/m2) (FLEP), on days 1, 2 and 3, every 22-28 days. 26 patients had locally advanced disease (LAD) and 12 had metastatic disease (M1). Oesophagectomy was planned for patients with LAD in case of tumour regression after chemotherapy, while patients with M1 disease received chemotherapy only. The overall remission rate was 45% (17/38) including four clinical and two pathologically confirmed complete remissions. 16 patients underwent oesophagectomy, 12 after response to FLEP, and 4 after FLEP and subsequent irradiation +/- 5-fluorouracil/mitomycin. Toxicity was mainly haematological, with WHO grade 3 and 4 leukocytopenia in 50% and thrombocytopenia in 31% of the patients. Two treatment-related deaths were observed; one due to chemotherapy and one postoperatively. Median survival time of LAD patients was 13 months, and actuarial 2-year survival was 31%. Patients with complete tumour resection after FLEP had a median survival time of 18 months and a 2-year survival rate of 42%. Median survival of M1 patients was 6 months. FLEP is an active combination for oesophageal cancer, especially when used preoperatively in LAD.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Esophageal Neoplasms; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Remission Induction; Thrombocytopenia; Treatment Outcome

The purpose of this prospective clinical trial was an attempt to find an effective and relatively non-toxic schedule for patients with metastatic breast cancer who decline to receive aggressive cytotoxic chemotherapy. A total of 36 patients with disseminated breast cancer were treated with mitoxantrone 8 mg/m2 intravenously (i.v.) day 1, folinic acid 400 mg/m2 in a 2-h i.v. infusion with 5-fluorouracil 500 mg/m2 as an i.v. bolus 1 h later, days 1 and 8 at 3-week intervals plus prednisone 20 mg/m2 orally daily with diminishing doses over several weeks. Objective regressions were observed in 24/36 (67%) patients, 9 being complete (25%). Responses were seen at all disease sites, mainly pleural/lung, bone and liver. The median duration of response was 8 months (range 4-25+) and the median survival 12 months (range 3-26+). Myelosuppression, mainly leucopenia and thrombocytopenia, was the major toxicity but without complications. Other toxicities included mild or moderate nausea and/or vomiting (50%), stomatitis (33%) and diarrhoea (11%). Alopecia was minimal. No cases of cardiotoxicity were detected. The substantial response rate obtained with this relatively well tolerated regimen against advanced breast cancer warrants its assessment in a larger number of patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Middle Aged; Mitoxantrone; Prednisone; Prognosis; Prospective Studies; Thrombocytopenia; Time Factors

5-Fluorouracil (5-FU) activity has been improved by the use of leucovorin (LV) or alpha-2a interferon (alpha-IF). We investigated the feasibility and activity of addition of alpha-IF to a 5-FU/LV regimen. A phase I study with 26 patients (14 previously untreated, 12 previously treated) with disseminated cancer was conducted. 15 patients were treated with 5-FU/LV and 11 with 5-FU/LV/alpha-IF. The 5-FU/LV regimen consisted of escalating doses of 5-FU bolus intravenously on days 2 and 3, combined with repeated oral LV on days 1, 2 and 3. Treatment was every 2 weeks. In the 5-FU/LV/alpha-IF schedule, 18 x 10(6) U alpha-IF subcutaneously daily was added on days 1, 2 and 3. The phase I study was followed by a phase II study of 5-FU/LV/alpha-IF at the established 5-FU dose in 29 previously untreated patients with disseminated colorectal cancer. The optimal 5-FU dose in both parts of the phase I study was 750 mg/m2/day. Mucositis, diarrhea and leucopenia were dose limiting. Although alpha-IF added its own toxicity (fever, flu-like symptoms, fatigue), it did not decrease the optimal dose of 5-FU. In the phase II study 28 patients were evaluable for response: three complete responses and 12 partial responses were observed (response rate 54%, 95% confidence interval, 34 to 72%). Pharmacokinetics of oral LV was performed in patients treated with and without alpha-IF: significantly higher serum levels of LV and 5-methyltetrahydrofolate were found after alpha-IF addition. Influence of alpha-IF on gastrointestinal absorption or renal clearance could be excluded. In conclusion, this 5-FU/LV/alpha-IF combination seems active in metastatic colorectal cancer. The pharmacokinetic interaction between alpha-IF and LV may play a role in the activity of this regimen. Controlled studies are necessary to establish the value of addition of alpha-IF to 5-FU/LV regimens.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Diarrhea; Feasibility Studies; Female; Fluorouracil; Humans; Interferon-alpha; Leucovorin; Leukopenia; Male; Middle Aged

38 patients with advanced breast adenocarcinoma were treated in a phase II study with 5-fluorouracil and high-dose folinic acid combined with cyclophosphamide and mitoxantrone. 6 patients had received prior chemotherapy for advanced disease, all with an anthracycline-containing regimen. Treatment was generally well tolerated. The most common side-effect was myelosuppression, with 1 toxic death due to leukopenia-related sepsis. 1 patient developed severe congestive heart failure 12 months from the end of therapy. 36 patients were evaluable for response. The overall response rate was 55%. Median duration of response was 8 months and median survival time was 16 months. This regimen warrants further investigations.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Drug Evaluation; Female; Fluorouracil; Heart Failure; Humans; Leucovorin; Leukopenia; Middle Aged; Mitoxantrone; Salvage Therapy; Thrombocytopenia

From September 1984 to July 1986, 70 previously untreated patients with Stage II to IV intermediate- or high-grade non-Hodgkin's lymphoma (according to the International Working Formulation) were enrolled in a phase III comparative trial. The objectives of the study were to compare the efficacy and safety of using mitoxantrone instead of doxorubicin in the combination chemotherapeutic regimen m-BACOD (intermediate-dose methotrexate, bleomycin, Adriamycin [doxorubicin, Adria Laboratories], cyclophosphamide, Oncovin [vincristine, Eli Lilly and Company], and dexamethasone). Seventy patients were randomly assigned to receive either m-BN (Novantrone; mitoxantrone, American Cyanamid Company) COD or m-BACOD. The complete-response rate was 57% in both treatment groups, and no significant differences in overall or relapse-free survival were recorded between the two groups. Patients treated with m-BACOD experienced severe alopecia more frequently (P less than .001) and reported six adverse cardiac events of grade greater than 1 whereas neither was observed among those receiving m-BNCOD. The mitoxantrone-containing regimen was found to have an equivalent efficacy and reduced clinical toxicity in comparison to the standard doxorubicin-containing regimen in patients with poor-prognosis non-Hodgkin's lymphomas.

Topics: Adult; Aged; Alopecia; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dexamethasone; Doxorubicin; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Leucovorin; Leukopenia; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Mitoxantrone; Mouth Mucosa; Neoplasm Staging; Neutropenia; Recurrence; Remission Induction; Stomatitis; Stroke Volume; Survival Rate; Vincristine

In a recent phase II trial we have shown a favorable response rate for sequential methotrexate-5-fluorouracil (MF) in advanced gastric and colorectal cancer. We determined the therapeutic effect of sequential MF in patients with advanced gastric cancer by comparing it to 5-fluorouracil alone (F) in a randomized multicenter trial. Since February 1987 to July 1988, 133 patients with advanced gastric cancer have been prospectively randomized to receive either MF (methotrexate 100 mg/m2 i.v. push, 5-fluorouracil 600 mg/m2 i.v. drip over 15 minutes one hour after methotrexate and leucovorin 15 mg p.o. q 6 hrs x 2 beginning 24 hrs after methotrexate) of F (the same 5-fluorouracil as described for MF). Each treatment was repeated weekly x 5, then q 2 weeks. The two treatment arms were balanced for 17 clinical characteristics. The response rate was 17.9% (10 of 56 patients) in the MF arm and 1.9% (one of 53 patients) in the F arm (p less than 0.01). Median duration of response was 6.8 weeks (MF) and 6 weeks (F), respectively. Median survival time was 7.9 months (MF) and 7.3 months (F) on interim findings. Leukocytopenia and GI toxicity were significantly more common in patients receiving MF, but the degree was similar for both arms. Other side effects were minimal and no different. This schedule of MF is more effective than F in inducing remission for patients with advanced gastric cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Drug Administration Schedule; Female; Fluorouracil; Humans; Japan; Leucovorin; Leukopenia; Male; Methotrexate; Middle Aged; Multicenter Studies as Topic; Nausea; Prospective Studies; Quality of Life; Random Allocation; Remission Induction; Stomach Neoplasms; Vomiting

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Colorectal Neoplasms; Diarrhea; Fluorouracil; Humans; Leucovorin; Leukopenia; Methotrexate; Random Allocation; Thrombocytopenia

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

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

The treatment-associated toxicity in 189 patients entered in the COSS-80 Study was analyzed. The sequential use of high-dose methotrexate (HDMTX) with citrovorum factor rescue (CFR) and cis-platinum may be additive or synergistic in causing renal toxicity. However, evaluation of the 48-h serum methotrexate level and the incidence of elevated serum creatinine levels throughout treatment failed to indicate prolonged methotrexate elimination or severe kidney damage from this regimen where an interval of 3 weeks between cis-platinum administration and the next course of HDMTX was mandatory. The treatment-related mortality was 3.2% (6 out of 189 patients). Three patients died of septicemia during chemotherapy-induced bone-marrow depression following treatment with adriamycin or the combination of bleomycin, cyclophosphamide, and dactinomycin (BCD). Three deaths occurred following the use of high-dose methotrexate with citrovorum factor rescue. Two of these deaths were associated with delayed excretion of methotrexate. The toxicity is within the range reported in the literature.

Topics: Acute Kidney Injury; Adolescent; Adult; Antineoplastic Agents; Body Weight; Bone Neoplasms; Child; Child, Preschool; Cisplatin; Clinical Trials as Topic; Drug Therapy, Combination; Female; Humans; Leucovorin; Leukopenia; Male; Methotrexate; Osteosarcoma

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

We have conducted a Phase 1 study of aminopterin (AMT) with leucovorin (LV) in 17 patients. AMT was administered by bolus injection every 7 to 14 days in dosages from 25 to 425 mg/sq m. LV rescue was instituted at 24 hr and continued for 48 to 72 hr. At dosages above 50 mg/sq m, we observed nephrotoxicity defined as greater than or equal to a 25% increase in serum creatinine 24 hr after AMT administration, but its incidence was not strictly dose related. Urinary alkalinization and volume expansion appeared to reduce the incidence of nephrotoxicity. Nephrotoxic drug courses were associated with 24-hr plasma AMT levels [3.6 +/- 2.0 (S.D.) X 10(-6) M] which were significantly higher than nonnephrotoxic courses (1.6 +/- 1.0 x 10(-6) M) (p less than 0.05). In nonnephrotoxic courses, serum elimination pharmacokinetics appeared to be biphasic with a t1/2 alpha of 1.08 +/- 0.01 hr and t1/2 beta of 12.31 +/- 0.06 hr. Systemic toxicity (myelosuppression and mucositis) could be prevented in patients with impaired AMT clearance by the administration of LV at an increased dose rate. In several courses, systemic toxicity occurred in spite of apparently normal plasma clearance, suggesting that 24-hr plasma levels may not accurately reflect intracellular drug effects. Cytokinetic studies on bone marrow aspirates allowed determination of the rescue effect of LV and may prove useful in predicting marrow protection.

Topics: Aminopterin; Bone Marrow; Clinical Trials as Topic; Drug Administration Schedule; Humans; Kidney; Leucovorin; Leukopenia; Methotrexate; Neoplasm Metastasis; Neoplasms; Solubility

Topics: Administration, Oral; Anemia; Antimalarials; Blood Platelets; Chloroquine; Clinical Trials as Topic; Folic Acid; Hematocrit; Humans; Leucovorin; Leukocyte Count; Leukopenia; Malaria; Male; Military Medicine; Placebos; Plasmodium falciparum; Pyrimethamine; Sulfisoxazole; Vietnam

Adjuvant chemotherapy is a standard treatment option for patients with stage III and high-risk stage II colon cancer. Sex is one of several factors responsible for the wide inter-patient variability in drug responses. Amalgamated data on the effect of sex on the toxicity of current standard adjuvant treatment for colorectal cancer are missing.. The objective of our study was to compare incidence and severity of major toxicities of fluoropyrimidine- (5FU or capecitabine) based adjuvant chemotherapy, with or without oxaliplatin, between male and female patients after curative surgery for colon cancer. Adult patients enrolled in 27 relevant randomized trials included in the ACCENT (Adjuvant Colon Cancer End Points) database, a large, multi-group, international data repository containing individual patient data, were included. Comparisons were conducted using logistic regression models (stratified by study and treatment arm) within each type of adjuvant chemotherapy (5FU, FOLFOX, capecitabine, CAPOX, and FOLFIRI). The following major toxicities were compared (grade III or IV and grade I-IV, according to National Cancer Institute Common Terminology Criteria [NCI-CTC] criteria, regardless of attribution): nausea, vomiting, nausea or vomiting, stomatitis, diarrhea, leukopenia, neutropenia, thrombocytopenia, anemia, and neuropathy (in patients treated with oxaliplatin).. Data from 34 640 patients were analyzed. Statistically significant and clinically relevant differences in the occurrence of grade III or IV nonhematological {especially nausea (5FU: odds ratio [OR] = 2.33, 95% confidence interval [CI] = 1.90 to 2.87, P < .001; FOLFOX: OR = 2.34, 95% CI = 1.76 to 3.11, P < .001), vomiting (5FU: OR = 2.38, 95% CI = 1.86 to 3.04, P < .001; FOLFOX: OR = 2.00, 95% CI = 1.50 to 2.66, P < .001; CAPOX: OR = 2.32, 95% CI = 1.55 to 3.46, P < .001), and diarrhea (5FU: OR = 1.35, 95% CI = 1.21 to 1.51, P < .001; FOLFOX: OR = 1.60, 95% CI = 1.35 to 1.90, P < .001; FOLFIRI: OR = 1.57, 95% CI = 1.25 to 1.97, P < .001)} as well as hematological toxicities (neutropenia [5FU: OR = 1.55, 95% CI = 1.37 to 1.76, P < .001; FOLFOX: OR = 1.96, 95% CI = 1.71 to 2.25, P < .001; FOLFIRI: OR = 2.01, 95% CI = 1.66 to 2.43, P < .001; capecitabine: OR = 4.07, 95% CI = 1.84 to 8.99, P < .001] and leukopenia [5FU: OR = 1.74, 95% CI = 1.40 to 2.17, P < .001; FOLFIRI: OR = 1.75, 95% CI = 1.28 to 2.40, P < .001]) were observed, with women being consistently at increased risk.. Our analysis confirms that women with colon cancer receiving adjuvant fluoropyrimidine-based chemotherapy are at increased risk of toxicity. Given the known sex differences in fluoropyrimidine pharmacokinetics, sex-specific dosing of fluoropyrimidines warrants further investigation.

Topics: Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Body Mass Index; Camptothecin; Capecitabine; Chemotherapy, Adjuvant; Colonic Neoplasms; Databases, Factual; Diarrhea; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Logistic Models; Male; Middle Aged; Nausea; Nervous System Diseases; Organoplatinum Compounds; Oxaliplatin; Randomized Controlled Trials as Topic; Sex Factors; Stomatitis; Thrombocytopenia; Vomiting

Data on FOLFIRINOX as a second-line chemotherapy for advanced pancreatic cancer are limited. In the JASPAC06 study-a nationwide, multicenter, observational study-FOLFIRINOX for patients with unresectable or recurrent pancreatic cancer as any line of treatment showed favorable efficacy and safety in Japanese clinical practice.. We performed exploratory analyses of patients with unresectable or recurrent pancreatic cancer who received FOLFIRINOX as the second-line chemotherapy in Japanese clinical settings.. Of the 399 evaluable patients, 44 were eligible for inclusion in the analysis. The patients' characteristics were as follows: median age, 62 years; men, 26 (59%); Eastern Cooperative Oncology Group-Performance status 0/1, 30 (68%)/14 (32%); disease status, recurrent/local/metastatic: 4 (9%)/8 (18%)/32 (73%). The initial dose was reduced in 28 (64%) patients. The median time to treatment failure and number of cycles were 4.5 (range, 0.2-19.1) months and 6 cycles (range, 1-13 or more), respectively. The major grade 3/4 adverse events were neutropenia in 29 (66%), leucopenia in 17 (39%), anorexia in 7 (16%), febrile neutropenia in 5 (11%), and anemia in 5 (11%) patients. The median overall survival, progression-free survival, and 1-year survival rates were 10.3 (95% confidence interval [CI], 7.2-13.3), 4.1 (95% CI, 2.6-5.5) months, and 30%, respectively.. Our findings suggest that FOLFIRINOX as a second-line chemotherapy for advanced pancreatic cancer was effective in patients with a good performance status. It displayed toxicity similar to that observed with its use as a first-line treatment.

Topics: Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Glucuronosyltransferase; Humans; Irinotecan; Japan; Kaplan-Meier Estimate; Leucovorin; Leukopenia; Male; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Oxaliplatin; Pancreatic Neoplasms; Progression-Free Survival; Survival Analysis; Treatment Outcome

Practice patterns of same-day versus next-day pegfilgrastim vary in numerous practice settings across the country. Current utilization with same-day pegfilgrastim reduced overall visits and reduced treatment time for chemotherapy administration.. To assess the efficacy and safety of same-day versus next-day pegfilgrastim in patients with colorectal cancer.. Patient data was extracted through electronic health records (EHR) search of ICD-9 codes that matched patients with CRC and treated with FOLFOX or FOLFIRI from November 2013 to January 2016. The incidence rates of primary and secondary endpoints were estimated for patients who received either FOLFOX or FOLFIRI and same-day pegfilgrastim with 2-sided 95% confidence intervals. Fisher's exact test for 2 × 2 contingency tables was used to compare the incidence of primary and secondary endpoints between the two study groups performed at the α = 0.05 significance level. A study by Hecht et al. served as a historical control for next-day pegfilgrastim.. A total of 109 out of an initial 330 patients with appropriate ICD-9 criteria were eligible for study inclusion. The primary endpoint of incidence of FN recorded over 4 chemotherapy cycles with either FOLFOX6 or FOLFIRI occurred in 3.7% of patients (95% CI, 1.1-9.4%). Secondary endpoints also occurred with a relatively low incidence: 13 patients developed grades 3/4 neutropenia (11.9%; 95% CI, 7.0-19.5%); 11 patients required dose reductions because of neutropenia or FN (10.1%; 95% CI, 5.6-17.3%); and 5 patients were hospitalized due to neutropenia or FN (4.6%; 1.7-10.6%). There were 4 reported events of FN (3.2%; 95% CI, 1.0-8.3%) for those who received next-day pegfilgrastim compared to 11 events in the placebo group (9.4%; 95% CI, 5.1-16.4%). The incidence of dose delays or dose reductions due to neutropenia or FN were 5 (4.1%, 95% CI, 1.5-9.4%) in the next-day pegfilgrastim group versus 26 (22.1%, 95% CI, 15.5-30.4%) in the placebo group.. The study was retrospective in design and utilized a historical control for the comparator.. Our study results suggest that same-day pegfilgrastim administration may be a safe and effective alternative to 24-h post-chemotherapy administration in patients with esophageal, gastric, appendiceal, or colorectal cancer undergoing treatment with FOLFOX or FOLFIRI.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Drug Administration Schedule; Febrile Neutropenia; Female; Filgrastim; Fluorouracil; Granulocyte Colony-Stimulating Factor; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Organoplatinum Compounds; Polyethylene Glycols; Recombinant Proteins; Retrospective Studies; Treatment Outcome

Irinotecan (CPT-11) is a drug used against a wide variety of tumors, which can cause severe toxicity, possibly leading to the delay or suspension of the cycle, with the consequent impact on the prognosis of survival. The main goal of this work is to predict the toxicities derived from CPT-11 using artificial intelligence methods. The data for this study is conformed of 53 cycles of FOLFIRINOX, corresponding to patients with metastatic colorectal cancer. Supported by several demographic data, blood markers and pharmacokinetic parameters resulting from a non-compartmental pharmacokinetic study of CPT-11 and its metabolites (SN-38 and SN-38-G), we use machine learning techniques to predict high degrees of different toxicities (leukopenia, neutropenia and diarrhea) in new patients. We predict high degree of leukopenia with an accuracy of 76%, neutropenia with 75% and diarrhea with 91%. Among other variables, this study shows that the areas under the curve of CPT-11, SN-38 and SN-38-G play a relevant role in the prediction of the studied toxicities. The presented models allow to predict the degree of toxicity for each cycle of treatment according to the particularities of each patient.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Diarrhea; Female; Fluorouracil; Forecasting; Glucuronates; Humans; Irinotecan; Leucovorin; Leukopenia; Machine Learning; Male; Middle Aged; Models, Biological; Neutropenia; Oxaliplatin; Topoisomerase I Inhibitors

The purpose of this study was to evaluate the feasibility and safety of ambulatory high-dose methotrexate (HDMTX) administration with oral hydration, alkalinization, and leucovorin rescue. HDMTX (12 g/m) was given intravenously over 4 hours after urine alkalinization. Families and patients were instructed to continue ambulatory oral hydration and alkalinization to monitor urine pH and to adjust bicarbonate according to our institution's treatment algorithm. Clinical status and MTX levels were controlled every 24 hours, and oral leucovorin dose was adjusted accordingly.. From April 2007 to December 2010, 150 of 447 courses of HDMTX (31.4%) were given on an outpatient basis, and 91.2% were successfully completed. The main causes of failure were poor oral tolerance (n=6) and fever (n=4). Most patients (81%) had MTX levels of <10 μmol/L 24 hours post-HDMTX; only in 1 course the levels were >50 μmol/L (50.96 μmol/L). Neutropenia grade III/IV was observed in 18.3% of the courses, grade III/IV leukopenia in 2.7%, and grade III/IV thrombocytopenia and anemia in 4.7%. Around 39% were associated with grade III/IV hepatic toxicity (asymptomatic hypertransaminasemia), grade III-IV gastrointestinal toxicity (vomiting and diarrhea) (5%), grade III-IV mucositis (4%), and none of the patients developed renal toxicity.. Ambulatory HDMTX administration is feasible and safe in a population with poor resources in a developing country.

Topics: Adolescent; Algorithms; Ambulatory Care; Anemia; Antacids; Argentina; Chemical and Drug Induced Liver Injury; Child; Diarrhea; Female; Humans; Hydrogen-Ion Concentration; Leucovorin; Leukopenia; Male; Methotrexate; Mucositis; Neutropenia; Osteosarcoma; Retrospective Studies; Thrombocytopenia; Vomiting

To quantify ensuing bone marrow (BM) suppression during postoperative chemotherapy resulting from preoperative chemoradiation (CRT) therapy for rectal cancer.. We retrospectively evaluated 35 patients treated with preoperative CRT followed by postoperative 5-Fluorouracil and oxaliplatin (OxF) chemotherapy for locally advanced rectal cancer. The pelvic bone marrow (PBM) was divided into ilium (IBM), lower pelvis (LPBM), and lumbosacrum (LSBM). Dose volume histograms (DVH) measured the mean doses and percentage of BM volume receiving between 5-40 Gy (i.e.: PBM-V5, LPBM-V5). The Wilcoxon signed rank tests evaluated the differences in absolute hematologic nadirs during neoadjuvant vs. adjuvant treatment. Logistic regressions evaluated the association between dosimetric parameters and ≥ grade 3 hematologic toxicity (HT3) and hematologic event (HE) defined as ≥ grade 2 HT and a dose reduction in OxF. Receiver Operator Characteristic (ROC) curves were constructed to determine optimal threshold values leading to HT3.. During OxF chemotherapy, 40.0% (n=14) and 48% (n=17) of rectal cancer patients experienced HT3 and HE, respectively. On multivariable logistic regression, increasing pelvic mean dose (PMD) and lower pelvis mean dose (LPMD) along with increasing PBM-V (25-40), LPBM-V25, and LPBM-V40 were significantly associated with HT3 and/or HE during postoperative chemotherapy. Exceeding ≥36.6 Gy to the PMD and ≥32.6 Gy to the LPMD strongly correlated with causing HT3 during postoperative chemotherapy.. Neoadjuvant RT for rectal cancer has lasting effects on the pelvic BM, which are demonstrable during adjuvant OxF. Sparing of the BM during preoperative CRT can aid in reducing significant hematologic adverse events and aid in tolerance of postoperative chemotherapy.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Bone Marrow Diseases; Capecitabine; Chemoradiotherapy; Female; Fluorouracil; Humans; Ilium; Leucovorin; Leukopenia; Logistic Models; Lumbar Vertebrae; Male; Middle Aged; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Pelvic Bones; Preoperative Care; Rectal Neoplasms; Retrospective Studies; ROC Curve; Sacrum; Statistics, Nonparametric; Thrombocytopenia

The present study aimed to determine the effect of oral β-glucan on mucositis and leukopenia in 62 consecutive patients with colorectal cancer treated with an adjuvant FOLFOX-4 regimen. The patients were retrospectively evaluated in 2 groups: one group received β-glucan and the other did not (control group). Leucocytes, neutrophils, and platelets were evaluated before and 1 week after chemotherapy and oral mucositis and diarrhea were noted. Leucocyte and neutrophil counts after chemotherapy in the β-glucan group were 7,300/mm3 and 3,800/mm3, respectively, and the reductions, as compared to baseline, were not significant (p=0.673 and 0.784). The median platelet count was 264,000/mm3 after chemotherapy in the β-glucan group and the reduction, as compared to baseline, was borderline significant (p=0.048). In the control group, reduction in leucocyte, neutrophil, and platelet counts was statistically significant. Oral mucositis and diarrhea were less common in the β-glucan group. We conclude that β-glucan can be used to reduce the adverse effects of chemotherapy.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; beta-Glucans; Chemotherapy, Adjuvant; Cohort Studies; Colorectal Neoplasms; Diarrhea; Female; Fluorouracil; Humans; Leucovorin; Leukocyte Count; Leukopenia; Male; Middle Aged; Mucositis; Organoplatinum Compounds; Platelet Count; Retrospective Studies; Stomatitis; Treatment Outcome

Phase II and III trials of docetaxel, cisplatin and fluorouracil (DCF) have shown superior efficacy versus cisplatin and fluorouracil alone but with high rates of hematologic toxicity in metastatic gastric cancer cases. To reduce toxicity while maintaining the efficacy of DCF, we investigated low dose docetaxel (D), cispatin (C) - leucovorin and fluorouracil (De Gramont regimen).. Chemotherapy-naive patients with metastatic gastric cancer (MGC) received D 60 mg/m2 on day 1 and cisplatin 30 mg/m2 on day 1-2 and the De Gramont regimen (Folinic acid 400 mg/m2 on day 1 and 5-FU 2400 mg/m2/46 h continuous infusion) every 3 weeks. The primary endpoint was response rate.. One hundred twenty patients with a median age of 52.5 years (range, 32-78) received a median of 6 cycles (range, 2-12 cycles). Of the 120 evaluable patients, 4 showed complete remission and 36 achieved a partial response. The overall response rate was 56.6%. Twenty eight patients (23.3%) showed stable disease and 52 (43.3%) progression. The median time to progression was 7 months (95%CI 6-7.9). The median overall survival was 15 months (95%CI 13.7-16.2). The most frequent hematological toxicity was leucopenia, which occurred at grade 3/4 intensity in 24 patients (20%).. Low-dose DC- De Gramont regimen is active in MGC with a tolerable toxicity profile.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease Progression; Disease-Free Survival; Docetaxel; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Retrospective Studies; Stomach Neoplasms; Taxoids; Treatment Outcome

We retrospectively analyzed comparative toxicities and efficacies of chemotherapy regimens in advanced gastric cancer (AGC) patients who achieved complete response (CR) after chemotherapy.. We reviewed the medical records of 1,203 patients, who were pathologically diagnosed as AGC in a single center between January 2001 and October 2007. On the basis of the Response Evaluation Criteria in Solid Tumors, CR was evaluated with abdominal computed tomography. Toxicities were evaluated using the National Cancer Institute's common toxicity criteria before each chemotherapy cycle.. Among the 1,203 AGC patients enrolled in this study, 568 received chemotherapy and 635 received best supportive care. The major chemotherapy regimens were 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX), docetaxel, cisplatin and 5-fluorouracil (DCF) and 5-fluorouracil, leucovorin and irinotecan (FOLFIRI). Among the 568 patients, 51 (9.0%) achieved CR (49 [8.6%] with FOLFOX [n=12], DCF [n=26], or FOLFIRI [n=11] and 2 [0.3%] with etoposide, leucovorin and 5-fluorouracil). For patients administered FOLFOX, DCF, and FOLFIRI, the median time to disease progression was 4 months (range, 1.8-59.5), 15 months (range, 2.9-31.2) and 10 months (range, 2.0-39.5), and the median survival times were 48 months (range, 5.9-74.0), 37 months (range, 14.0-86.0), and 30 months (range, 6.0-50.0), respectively. Grades 3-4 mucositis occurred mostly in patients administered DCF (n=8, 30.8%). Grades 3-4 leucopenia were observed in 1 (8.3%), 11 (42.3%), and 4 (36.4%) patients administered FOLFOX, DCF and FOLFIRI, respectively. No statistically significant differences were observed in the 3 regimens.. All 3 regimens (FOLFOX, DCF and FOLFIRI) were active and tolerable. Their efficacies and toxicities were not significantly different.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Docetaxel; Drug Therapy, Combination; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Mucositis; Nausea; Neoplasm Staging; Organoplatinum Compounds; Retrospective Studies; Stomach Neoplasms; Survival Rate; Taxoids; Tomography, X-Ray Computed; Vomiting

To evaluate the efficacy and toxicity of oxaliplatin-based regimen in patients with advanced or metastatic gastric/esophagogastric junction cancer (AGC).. The clinicopathological data of a total of 180 patients with AGC were retrospectively analyzed. Responses was evaluated by RECIST criteria, and toxicity were assessed according to the NCI-CTC AE version 3.0.. 155 patients received mFOLFOX regimen, and 25 patients received regimens of mEOF and CapOX, with a total chemotherapy of 717 cycles with a median of 3 cycles. The therapeutic response was evaluated in 150 patients, showing response rate (RR) of 30.0% and disease control rate (DCR) of 74.0%. The response was evaluated in 103 of 124 patients who received the therapy as 1st line, with RR of 34.0%, DCR of 74.8%, and overall survival of 11.3 months. The major grade III/IV adverse events were leucocytopenia (14.4%), neutropenia (17.8%), thrombocytopenia (3.8%), nausea/vomiting (8.9%), and peripheral neuropathy (2.2%), with no treatment related death.. Oxaliplatin-based regimen is active and well tolerated in patients with advanced or metastatic gastric/esophagogastric junction cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Esophagogastric Junction; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Nausea; Neoplasm Staging; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Remission Induction; Retrospective Studies; Stomach Neoplasms; Survival Rate; Thrombocytopenia; Vomiting

Topics: Antimetabolites, Antineoplastic; Diarrhea; Dihydrouracil Dehydrogenase (NADP); Fluorouracil; Genetic Predisposition to Disease; Genetic Testing; Humans; Leucovorin; Leukopenia; Logistic Models; Methylenetetrahydrofolate Reductase (NADPH2); Mucositis; Odds Ratio; Patient Selection; Polymorphism, Genetic; Predictive Value of Tests; Risk Assessment; Risk Factors; Severity of Illness Index; Thymidylate Synthase; Vitamin B Complex

We evaluated the efficacy and safety of modified FOLFIRI for patients with refractory advanced or recurrent colorectal cancer. Modified FOLFIRI was given 29 patients (21 men and 8 women, with a median age of 61.0 years) from 2 to 16 times (median 10.0). 19 out of 29 patients were colon cancer, and the other 10 were rectal cancer. 18 patients were administered as first-line chemotherapy, and 11 were more than second line. CPT-11 was administered at a dose of under 150 mg/m(2), to remain within the limits in Japan. The response to treatment was CR in 3 patients, PR in 8, and SD in 12. The response rate was 37.9%. Grade 4 hematologic toxicities included leukocytopenia in 2 patients, neutropenia in 7 and anemia in 1. Grade 3/4 non-hematologic toxicities included febrile neutropenia in 4 patients, anorexia in 3, fatigue in 3, and nausea, diarrhea and interstitial pneumonia in 1. Except in 2 patients, all reactions could be controlled with the use of G-CSF or by setting drug holiday. In summary, modified FOLFIRI is a safe and effective regimen even at a dose of under 150 mg/m(2), of CPT-11. It can be given with good tolerance for patients with refractory advanced or recurrent colorectal cancer on an outpatient basis with due care especially for neutropenia.

Topics: Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Drug Administration Schedule; Feasibility Studies; Female; Fluorouracil; Humans; Infusion Pumps, Implantable; Infusions, Intravenous; Irinotecan; Leucovorin; Leukopenia; Male; Middle Aged; Neutropenia; Quality of Life; Rectal Neoplasms

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

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

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

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

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

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

Concomitant treatment with 5-fluorouracil (5-FU) and Leucovorin (LV) is positioned as the standard chemotherapy against colorectal cancer. We noted the action of LV to enhance the effect of biochemical modulation by 5-FU, and made an attempt at home chemotherapy with UFT + LV by oral administration, in consideration to the convenience of patients.. The subjects of this study were 24 post-operative patients who had been assessed with Dukes D and curability C colorectal cancer with measurable metastatic lesions and who could tolerate chemotherapy.. 1 course of treatment consisted of 2 weeks of UFT at 300-400 mg/m2/day and LV at 15 mg/body/day followed by 2 weeks of drug withdrawal. The administration was conducted for 4 courses or more as the target. Unless serious adverse reaction occurred, dose increase of UFT was allowed.. The efficacy rate in the 22 patients who were assessable was 22.7%. There were 11 NC patients, accounting for half (50%) of the subjects. This home chemotherapy is expected to become an alternative chemotherapy against colorectal cancer in the future, because the treatment does not require hospitalization and has less impact on the QOL of patients.

Topics: Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Diarrhea; Drug Administration Schedule; Drug Combinations; Female; Home Care Services, Hospital-Based; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Nausea; Postoperative Care; Tegafur; Uracil; Vomiting, Anticipatory

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

In patients with liver metastases from colorectal cancer, survival can be increased by hepatic resection. Treatment with hepatic arterial infusion (HAI) and systemic chemotherapy following resection may further increase survival and decrease recurrence, but may also result in hepatic and systemic toxicity. This article will address the question of whether large hepatic resections resulting in a greater loss of healthy liver predisposes patients to developing toxicity from the subsequent chemotherapeutic regimens.. Retrospective analysis of 88 patients who underwent liver resection of colorectal metastases followed by adjuvant HAI and systemic chemotherapy and whose computerized tomography (CT) scans were done at Memorial Sloan-Kettering Cancer Center (MSKCC). Liver volumes were calculated from CT scans and used to determine the percentage change in healthy liver volume between the pre- and post-operative CT scans. Hepatic and systemic toxicities were defined according to the Common Toxicity Criteria of the National Cancer Institute.. Patients experienced a mean percentage decrease in healthy liver tissue of 17% (range: 57% decrease to 32% increase) at an estimated 1 month after resection and at the initiation of chemotherapy. In a logistic regression model using percentage change in the healthy liver volume as a continuous variable, no significant association was revealed between percentage of healthy liver resected and diarrhea (P = 0.47), leukopenia (P = 0.37), neutropenia (P = 0.31), high bilirubin (P = 0.27), or alkaline phosphatase (P = 0.79).. A greater loss of healthy liver following resection of hepatic metastases from colorectal cancer does not seem to predispose to the development of toxicity from adjuvant HAI and systemic chemotherapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Colorectal Neoplasms; Diarrhea; Drug Administration Schedule; Female; Fluorouracil; Hepatectomy; Hepatic Artery; Humans; Infusions, Intra-Arterial; Irinotecan; Leucovorin; Leukopenia; Liver; Liver Neoplasms; Male; Middle Aged; Neutropenia; Retrospective Studies

The efficacy and toxicity of 5-FU was various in different patients. It was reported that they were correlated to the activity of dihydropyrimidine dehydrogenase (DPD). This study is to measure DPD activity in blood and to analyze the relationship among DPD activity, the toxicity of 5-FU based adjuvant chemotherapy and the 5-FU plasma concentration in colorectal cancer patients.. 30 colorectal cancer patients were enrolled into the study to receive adjuvant chemotherapy 2 weeks after cured resection. The regimen was 5-FU 425 mg/m(2) plus CF 60 mg/m(2) continuous infused for 2 hours, daily for 5 days. The concentration of endogenous uracil (U) and dihydrouracil (UH(2)) were assayed by high performance liquid chromatography (HPLC). The UH2-U ratio in plasma was used to represent DPD activity in blood. The plasma samples were collected before chemotherapy in all patients to detect the DPD activity in blood, and after 5-FU infusion at day 1 and day 5 to measure 5-FU plasma concentration. The relationship among the DPD activity in blood, the toxicity of chemotherapy and the plasma concentration of 5-FU in all patients were analyzed.. 30 colorectal cancer patients have received adjuvant chemotherapy. The DPD activity in the blood of 30 colorectal cancer patients before chemotherapy was 4.09+/-1.21 (2.14-6.7), showed a trend of normal distribution. The 5-FU plasma concentration after 5-FU infusion was (2 079.12+/-621.41) microg/L (1 200.10-3 554.80 microg/L) at the first day, and (2 197.64+/-606.78) microg/L at the fifth day (1 259.00-3 441.03 microg/L). There was a negative relationship between the DPD activity in blood and the 5-FU plasma concentration at day 1 (r=-0.773, P=0.00), and day 5 after 5-FU infusion(r = -0.833, P = 0.00). No significant difference between the 5-FU plasma concentration of day 1 and day 5 was found (P=0.458). The 5-Fu associated toxicities had a negative relationship with DPD activity in blood, and had a positive relationship with 5-FU plasma concentration (P< 0.05).. The results indicated that the DPD activity in blood can be used to predict the toxicity and the 5-FU plasma concentration in patients with 5-FU based chemotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colonic Neoplasms; Dihydrouracil Dehydrogenase (NADP); Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Rectal Neoplasms

Irinotecan (CPT11) has established activity against advanced colorectal cancer without cross-resistance with 5-fluorouracil + leucovorin-based therapy. We conducted this pilot study to evaluate the efficacy and tolerance of combination treatment with irinotecan and 5-fluorouracil (5-FU) for patients in whom combination treatment with oxaliplatin with 5-FU + leucovorin has failed.. Patients were enrolled in this study after oxaliplatin treatment had failed. The treatment protocol consisted of CPT11 (180 mg/m(2) for 90 min) on day 1 and a 2 h infusion of 200 mg/m(2) leucovorin followed by 400 mg/m(2) 5-FU as an intravenous bolus injection plus a 22 h continuous infusion of 600 mg/m(2) 5-FU. This regimen was repeated for two consecutive days every 2 weeks.. A total of 18 patients were eligible for this study and in total 144 cycles of therapy (median eight cycles) were given to these patients. Four patients (22.2%; 95% CI: 8-36.4%) achieved an objective response of partial remission (PR) and an additional seven obtained stable disease (SD) status or minor response. The median duration of response was 8 months and 14 patients were alive at the end of the study. Hematological toxicity (neutropenia) was the most common serious side effect (29.2%), followed by gastrointestinal effects (diarrhea, 28.5%). Grade II-III diarrhea was experienced for at least one cycle by each patient.. The results of treatment for patients after oxaliplatin failure are encouraging and this treatment protocol is also well tolerated by previously heavily treated patients.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Drug Administration Schedule; Fluorouracil; Humans; Irinotecan; Leucovorin; Leukopenia; Middle Aged; Nausea; Pilot Projects; Rectal Neoplasms; Salvage Therapy; Survival Analysis; Treatment Outcome; Vomiting, Anticipatory

Colorectal cancer is a common malignancy. Surgical resection is the primary treatment modality and the outcome is closely related to the extent of the disease at presentation. Adjuvant chemotherapy with 5-fluorouracil and leucovorin is the standard therapy for resected node-positive disease. This therapy can cause myelosuppression. We present a case of colon cancer with idiopathic leukopenia who tolerated chemotherapy without worsening of leukopenia.

Topics: Chemotherapy, Adjuvant; Colonic Neoplasms; Fluorouracil; Humans; Leucovorin; Leukopenia; Male; Middle Aged

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

In the conduct of a clinical trial, unexpectedly high rates of toxicity may cause a researcher to want to terminate the trial early even though no formal stopping rule had been specified. The experience of one such clinical trial is used as an example of the ways in which group sequential methodology can be applied in deciding to stop the study, as well as in reporting the results of the clinical trial. This approach is then compared to a Bayesian analysis.

Topics: Antidotes; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Biometry; Clinical Trials as Topic; Fluorouracil; Granulocyte Colony-Stimulating Factor; Humans; Incidence; Leucovorin; Leukopenia; Mathematics; Models, Statistical; Mouth Diseases; Mouth Mucosa; Neoplasms; Research Design

A total of 44 women with advanced breast cancer who had failed first- and second-line chemotherapy were given combination chemotherapy consisting of folinic acid (FA), 5-fluorouracil (5-FU) and mitomycin C (MMC). The treatment schedule was: 200 mg/m2 FA and 400 mg/m2 5-FU given i.v. over 2 h for 5 days plus 5 mg/m2 MMC given i.v. on days 3-5; in 19 patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 3-4 and bone marrow depression, the MMC dose was 3 mg/m2 given i.v. on days 3-5. In all, 41 patients were evaluable for response; 15 had a partial remission (PR), 18 had stable disease (SD), and 8 showed progressive disease (PD). The median response duration was 6 months and the median survival was 10 months. Toxicity was mild and consisted mainly of stomatitis, diarrhea, and leukopenia. A rapid improvement in performance status was noted in responding patients. A striking result was the reduction of analgesics in most cases and their complete withdrawal in responding patients. This combination chemotherapy achieved satisfactory effectiveness and improved the quality of life of patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Diarrhea; Drug Evaluation; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Middle Aged; Mitomycin; Palliative Care; Remission Induction; Stomatitis

The dose intensity in cancer monochemotherapy is probably the most important prognostic factor. In combination chemotherapy, in which interactions between agents do occur, response, survival, and toxicity might vary between different schedules. In a literature review of all published data of folinic acid and 5-fluorouracil intravenous bolus therapy in colorectal cancer with comparable dose intensity, an attempt was made to characterize the possible differences of the variations of schedules used. The antitumor activity increased significantly from 19% to 30%-35% when the two drugs were used concomitantly in multiple fractions per cycle rather than on a single day. However, fractionation changed the type of dose-limiting toxicity from hematologic and neurologic to gastrointestinal side effects. The different schedules did not differ significantly in the overall frequency of severe toxicities; however, recommending a certain schedule outside of controlled trials should be done cautiously.

Topics: Clinical Trials as Topic; Colorectal Neoplasms; Diarrhea; Drug Administration Schedule; Fluorouracil; Heart; Humans; Leucovorin; Leukopenia; Neoplasm Staging

Topics: Acquired Immunodeficiency Syndrome; Drug Therapy, Combination; Humans; Leucovorin; Leukopenia; Pneumonia, Pneumocystis; Quinazolines; Trimetrexate

Advances in the management of gestational trophoblastic tumor have been made during the last three decades. Individualization of the therapy is one of the major advances. A number of risk factors has proved to predict accurately the prognosis of each patient. A few systems were currently in use, but difficult in putting them to practical use in the different geographical areas. At National Taiwan University Hospital from 1965 to 1979, 65 patients treated by chemotherapy were analyzed with respect of various prognostic factors. The score was assigned according to the mortality rate of each item to each prognostic factor, and thus established a scoring system which is suitable for the use in Taiwan. After establishment of our scoring system, 51 patients from 1980 to 1986 were treated according to the system and the appropriate therapeutic regimens. The outcome of these patients and toxicity of the different therapeutic regimens are presented.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Choriocarcinoma; Cyclophosphamide; Doxorubicin; Drug Evaluation; Etoposide; Female; Humans; Leucovorin; Leukopenia; Liver; Mercaptopurine; Methotrexate; Middle Aged; Pregnancy; Pregnancy Complications, Neoplastic; Prognosis; Remission Induction; Risk Factors; Taiwan; Trophoblastic Neoplasms; Uterine Neoplasms

A few reports have documented overdoses of vincristine sulfate. The present report describes our experience with serious complications of a vincristine overdose in an 18-year-old female who had methotrexate-resistant invasive mole. The patient received VAC therapy as the second line chemotherapy after 2 courses of MTX therapy. In the 6th course of VAC therapy, she was given 5 consecutive daily doses of VCR by mistake. On the 5th day of this VAC therapy, she showed the following toxic symptoms: abdominal pain, lumbago, insomnia, bleeding tendency, absence of motor reflex, leukopenia, and paralytic ileus. These symptoms led to realization of the VCR overdose. Leucovorin calcium administration and supportive treatment were carried out. Although it was difficult to evaluate the efficacy of leucovorin calcium on the vincristine toxic symptoms, she recovered and was discharged on the 36th hospital day.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Dactinomycin; Female; Humans; Hydatidiform Mole, Invasive; Leucovorin; Leukopenia; Paralysis; Parenteral Nutrition, Total; Pregnancy; Uterine Neoplasms; Vincristine

Seventy-eight individuals previously treated with chemotherapy for non-Hodgkin's lymphoma were enrolled in a phase II pilot study employing methotrexate 100 mg/M2 iv (day 1), calcium leucovorin 10 mg/M2 iv and/or po q6h (days 2-4), VM-26 (teniposide) 100 mg/M2 iv (days 2 and 9), procarbazine 100 mg/M2 po (days 2-15), and dexamethasone 15 mg/M2po (days 2-8) (MV26PD). Thirty percent of the 78 patients treated had a response to therapy (8% complete, 22% partial). Twenty-four percent of patients with diffuse histiocytic (large cell) lymphoma had a response (12% complete, 12% partial). The estimated failure-free survival was 41% at 3 months and the median survival (death from any cause) was 4.5 months for the entire cohort. Two individuals, including one individual with diffuse histiocytic lymphoma, remain in a complete response for over 900 days. Significant hematologic toxicity and infectious complications were seen in this heavily pretreated group of patients. MV26PD represents an active combination of agents for the treatment of non-Hodgkin's lymphoma. The optimal dosing for MV26PD remains to be determined.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Cytarabine; Dexamethasone; Drug Evaluation; Female; Humans; Leucovorin; Leukopenia; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Neutropenia; Procarbazine; Teniposide; Thrombocytopenia; Vincristine

12 AIDS/ARC patients with or suspected of Pneumocystis carinii pneumonia were treated with co-trimoxazole and received supplementary folic or folinic acid to avoid peripheral blood cytopenia. Most patients developed decreased numbers of neutrophils and hemoglobin while receiving co-trimoxazole. Supplementary folate/folinate could not abolish the drug-induced cytopenia. Routine prescription of folinic acid is not recommended. Folic acid is cheap and may be beneficial and should be prescribed.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Complex; Anemia; Drug Combinations; Folic Acid; Hematologic Diseases; Humans; Leucovorin; Leukopenia; Pneumonia, Pneumocystis; Prospective Studies; Sulfamethoxazole; Thrombocytopenia; Time Factors; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

We have treated 76 patients with locally advanced breast cancer, 31 with stage IIIA, 41 with stage IIIB, and 4 with stage IV disease, with primary induction chemotherapy including an attempted hormonal synchronization in 70 patients. All were treated to maximum objective clinical response before proceeding to any local therapy. Patients achieving a complete response with a negative repeat biopsy generally received radiation therapy while patients with residual disease, partial response (PR) or no change (NC) status received debulking surgery prior to radiation therapy. Regardless of response to induction chemotherapy, patients received at least 6 additional months of chemotherapy following local therapy. Initial doses of combination chemotherapy were escalated to targeted myelosuppression. The objective response rate to induction chemotherapy was 93% with 49% complete response (CR), 44% PR, and 7% NC. The median numbers of cycles of chemotherapy to achieve a CR, PR, or NC were 5, 3, and 5, respectively. Three patients who currently have PRs are still on chemotherapy with continued tumor regression. Of 37 patients achieving a CR to chemotherapy, 35 were assessed by biopsies to determine pathological evidence of response. Twenty-three of the 37 patients (62%) were proven to be complete responders with negative biopsies. Twenty-four patients have relapsed, 6 with stage IIIA, 16 with stage IIIB, and 2 with stage IV. Five patients have had locoregional relapses alone, 4 locoregional and distant, and 15 distant alone. Median time to progression is 35.9 months for stage IIIA and 34.2 months for stage IIIB. Median survival is 35.3 months for stage IIIB and is indeterminate for stage IIIA. This aggressive primary chemotherapy regimen with hormonal synchronization followed by local therapy appears to provide excellent local control and encouraging early results on systemic disease control.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Estrogens, Conjugated (USP); Fluorouracil; Heart Failure; Humans; Leucovorin; Leukopenia; Methotrexate; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Tamoxifen

Daily administration of 1 mg of folinic acid to immunosuppressed rats with incipient or established Pneumocystis carinii pneumonia did not impair the capacity of trimethoprim-sulfamethoxazole to either prevent or treat this disease. These observations constitute the first experimental support for the use of folinic acid to prevent or control cytopenias that occur in patients with Pneumocystis carinii pneumonia who are under trimethoprim-sulfamethoxazole treatment.

Topics: Animals; Dexamethasone; Drug Combinations; Drug Interactions; Immunosuppression Therapy; Leucovorin; Leukopenia; Male; Pneumocystis; Pneumonia, Pneumocystis; Random Allocation; Rats; Rats, Inbred Strains; Sulfamethoxazole; Tetracycline; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Encouraging results have recently been reported for studies using folinic acid in combination with 5-fluorouracil (5-FU) in the treatment of patients with gastrointestinal (GI) malignancies. Thirty-six patients with advanced colorectal cancer with unequivocal evidence of progression while treated with fluoropyrimidines were treated with a six-day continuous infusion of 500 mg/m2/d of folinic acid initiated 24 hours before a five-day course of 5-FU administered as an intravenous (IV) bolus of 370 mg/m2/d. An initial dose of 250 mg/m2/d of 5-FU was used in patients previously treated with ionizing radiation and/or a nitrosourea. Three objective partial responses were observed. The overall median duration of survival was 8.1 months. Toxicity was acceptable and not in excess of that expected for 5-FU alone.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Drug Evaluation; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Nausea; Rectal Neoplasms; Stomatitis; Thrombocytopenia

Twenty-three patients with metastatic breast carcinoma were induced with a complex systemic therapy regimen in an attempt to ascertain if a complete remission rate greater than 50% could be obtained with intensive drug exposure. The durability of the remissions was observed by discontinuing therapy after 3 cycles in complete remission or after 6 cycles of treatment, whichever was longer. In 13 patients consolidation radiation therapy to the pre-treatment sites of disease was administered after discontinuing systemic therapy. Each 28 day cycle of the drug regimen consisted of pulses of adriamycin, vincristine, dibromodulcitol, prednisone, methotrexate with leukovorin rescue, hexamethylmelamine, bleomycin (discontinued after entry #17), fluoxymesterone, and tamoxifen. Eighteen of the 23 patients achieved complete remissions (78%) and 3 had partial remissions. The median times to treatment failure and survival were, respectively, 12.3 and 19.4 mos. The times for complete remission patients were, respectively, 13.5 and 23.9 mos. Consolidation radiotherapy at greater than or equal to 40 Gy to drug induced pre-study sites of complete remission was associated with first relapses at pre-study sites in 5/30 (17%) instances, compared to 21/35 (60%) in sites not receiving radiotherapy. Side-effects were commensurate with the intensity of the treatment program and are detailed in the text. Although the achievement of a high complete remission rate is promising, the failure to extend their duration beyond that of historical data suggests that additional conceptual and therapeutic approaches need to be explored.

Topics: Altretamine; Antineoplastic Agents; Bleomycin; Breast Neoplasms; Combined Modality Therapy; Doxorubicin; Drug Administration Schedule; Female; Fluoxymesterone; Humans; Leucovorin; Leukopenia; Lung; Methotrexate; Mitolactol; Neoplasm Metastasis; Prednisone; Receptors, Estrogen; Tamoxifen; Thrombocytopenia; Time Factors; Vincristine

Topics: Acquired Immunodeficiency Syndrome; Drug Combinations; Humans; Leucovorin; Leukopenia; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

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

A new treatment program was developed in an attempt to increase the complete remission rate and survival of previously untreated patients with advanced stages of diffuse aggressive lymphomas. A flexible number of cycles of ProMACE chemotherapy (prednisone, methotrexate, doxorubicin, cyclophosphamide, and epipodophyllotoxin VP-16) was alternated with a flexible number of cycles of MOPP chemotherapy (mechlorethamine, vincristine sulfate, procarbazine, and prednisone), and finally late intensification with ProMACE therapy was given. The duration of each phase of treatment was determined by the patient's rate of tumor response. Complete remissions were achieved in 55 of 74 patients (74%) with a median duration of follow-up exceeding 2 1/2 years. Only ten of the complete responders (18%) have had relapse. The dose-limiting toxicity is myelosuppression, and eight patients (10%) died from sepsis. Median survival for all patients has not been reached but is predicted to exceed 4 years with 65% of patients alive at 4 years. Previously we achieved a 46% complete remission rate with 38% of all patients alive at 4 years; relapse-free survival beyond 2 years was tantamount to cure. Therefore, ProMACE-MOPP chemotherapy represents a substantial improvement in treating patients with diffuse aggressive lymphomas.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Blood Platelets; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Drug Therapy, Combination; Etoposide; Female; Humans; Leucovorin; Leukopenia; Lymphoma; Male; Mechlorethamine; Methotrexate; Middle Aged; Prednisone; Procarbazine; Vincristine

We have shown previously that methotrexate pretreatment of murine leukemia and human colon carcinoma cell cultures results in augmented intracellular accumulation of 5-fluorouracil metabolites. Both of these drugs are commonly used for the treatment of women with breast cancer; thus, sequencing of methotrexate before 5-fluorouracil was evaluated in vitro using a human mammary carcinoma cell line, 47-DN. Intracellular 5-fluorouracil accumulation was maximally increased 4-fold in cultures pretreated with 10 microM methotrexate for 24 hr. This enhancement of 5-fluorouracil metabolism was associated with increased intracellular levels of 5-phosphoribosyl 1-pyrophosphate, resulting from the antipurine effect of methotrexate. Brief exposure to exogenous hypoxanthine at physiological concentrations reversed the biochemical synergism between methotrexate and 5-fluorouracil. Other antimetabolites associated with elevations of 5-phosphoribosyl 1-pyrophosphate enhanced intracellular accumulation of 5-fluorouracil up to 2.5-fold. In cloning assays, 18 hr of methotrexate pretreatment followed by 5-fluorouracil resulted in optimal synergistic cytotoxicity, which could be prevented if high concentrations of leucovorin were given between methotrexate and 5-fluorouracil administration. Since these results indicated that optimal breast tumor toxicity in vitro was achieved by 18- to 24-hr sequencing of methotrexate and 5-fluorouracil, clinical toxicity study was carried out to assess whether this drug schedule could be tolerated. Seven patients with advanced cancer were treated with 21 courses of sequential therapy. No toxicity occurred with 38% of treatment courses; mild to moderate leukopenia and mucositis occurred with 29 and 38% of courses respectively. Toxicity was related to treatment interval and not cumulative drug dose or elevated serum methotrexate levels. These clinical results suggest that Phase II studies evaluating 24-hr-sequenced methotrexate and 5-fluorouracil in breast cancer are warranted.

Topics: Breast Neoplasms; Cell Line; Drug Administration Schedule; Drug Evaluation; Drug Interactions; Drug Synergism; Female; Fluorouracil; Humans; Hypoxanthines; Leucovorin; Leukopenia; Methotrexate; Nausea; Phosphoribosyl Pyrophosphate; Time Factors

Sixteen patients with resistant non-Hodgkin's lymphoma were treated with continuous infusions of vincristine (1-2 mg/m2 daily X 2 days) and bleomycin (0.25 mg/kg bolus dose, then 0.25 mg/kg/daily X 5 days). Responding patients received high dose methotrexate (1500 mg/m2) with citrovorum rescue on days 15, 22, 29, 36. Treatment cycles were repeated every six weeks in responding patients. The response frequency was 50% (three complete and five partial responses). Median response duration was 29 weeks. Major toxicity included stomatitis (63%) and leukopenia (44%). One episode each of possible hypersensitivity pneumonitis and paralytic ileus occurred. Continuous infusions of vincristine and bleomycin should be studied further in less critically ill patients.

Topics: Adult; Aged; Bleomycin; Drug Administration Schedule; Drug Therapy, Combination; Female; Fever; Humans; Infusions, Parenteral; Leucovorin; Leukopenia; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Stomatitis; Time Factors; Vincristine

Topics: Adult; Female; Humans; Leucovorin; Leukopenia; Pyrimethamine; Thrombocytopenia; Toxoplasmosis, Ocular

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

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

200 mg/m2 methotrexate given intravenously in a running drip for 6 h has been used as an initial adjuvant therapy in 38 patients with advanced head and neck cancer. The response rate is as high as 80%, with 21% achieving complete remission. Histologically, specimens were tumor free in 3 patients. Toxicity in 38 patients included leukopenia (4), mucositis (6) and diarrhea (1). This particular dose of methotrexate appears to be safe and usually does not need leucovorin rescue. Also, when given as initial treatment, it is effective in reduction of tumor bulk. A prolonged randomized trial is essential to determine its role in improving long-term survival.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Diarrhea; Female; Head and Neck Neoplasms; Humans; Leucovorin; Leukopenia; Male; Methotrexate; Middle Aged; Mucous Membrane

Topics: Antineoplastic Agents; Cyclophosphamide; Cytarabine; Doxorubicin; Humans; Leucovorin; Leukopenia; Lymphoma, Large B-Cell, Diffuse; Methotrexate; Prednisone; Procarbazine; Radiotherapy, High-Energy; Thrombocytopenia; Vincristine

The occurrence of overall toxicity was analyzed for 43 patients with osteosarcoma who received 349 high-dosage courses of methotrexate (HD-MTX) with citrovorum factor (Leukovorin) "rescue" (CF). The dosages of HD-MTX ranged from 50 to 350 mg/kg. Overall toxicity was assessed on the basis of five manifestations of toxicity: stomatitis, dermatitis, myelosuppression, liver dysfunction, and kidney function abnormalities. The great majority (91.4%) of the infusions were well tolerated, but 8.6% were associated with moderate or severe toxicity. Stomatitis and serum glutamic-oxaloacetic transaminase (SGOT) changes were the most frequent postinfusion findings. Three patients died from causes related to MTX toxicity. Dose, age, sex, and number of prior infusions were investigated by logistic regression analysis for prognostic effect on frequency of moderate to severe overall toxicity. Age and number of prior infusions had significant (P less than 0.06) effects on overall toxicity. Patients older than 15 years with greater than 10 prior infusions constituted the "high risk" group with a risk of moderate to severe toxicity 6.3 times that of the younger patients with fewer than 10 infusions.

Topics: Adolescent; Age Factors; Bone Marrow; Bone Neoplasms; Child; Dermatitis; Drug Administration Schedule; Female; Humans; Kidney; Leucovorin; Leukopenia; Liver; Male; Methotrexate; Osteosarcoma; Sex Factors; Stomatitis; Thrombocytopenia; Vincristine

High-dose methotrexate was given to 28 patients with advanced malignant melanoma who had previously failed to respond to two chemotherapy protocols. There were five instances of serious, but not fatal, toxicity. One patient has had an objective response and seven patients have had stabilization of disease with an average duration of 4 months.

Topics: Adult; Aged; Female; Humans; Intestinal Neoplasms; Leucovorin; Leukopenia; Male; Melanoma; Methotrexate; Middle Aged; Skin Neoplasms

The results of treating 59 patients with advanced carcinoma of the cervix with Adriamycin and methotrexate are given. Five combinations of the two cytotoxic drugs have been evaluated, differing only with regard to the methotrexate. One particular regimen has been shown to be effective with a relatively high remission rate coupled with a low rate of side effects.

Topics: Alopecia; Doxorubicin; Drug Administration Schedule; Drug Therapy, Combination; Female; Gastrointestinal Diseases; Humans; Leucovorin; Leukopenia; Methotrexate; Mouth Diseases; Remission, Spontaneous; Taste Disorders; Ulcer; Uterine Cervical Neoplasms

Topics: Bone Marrow; Bone Marrow Diseases; Humans; Leucovorin; Leukopenia; Pyrimidines; Thrombocytopenia

Topics: Adult; Aged; Anemia; Carcinoma, Squamous Cell; Cell Division; Drug Eruptions; Drug Synergism; Facial Neoplasms; Female; Head and Neck Neoplasms; Humans; Laryngeal Neoplasms; Leucovorin; Leukopenia; Lip Neoplasms; Male; Methotrexate; Middle Aged; Mouth Neoplasms; Mucous Membrane; Palatal Neoplasms; Pharyngeal Neoplasms; Tongue Neoplasms

Topics: Adenocarcinoma, Mucinous; Adult; Aged; Carcinoma, Squamous Cell; Female; Head and Neck Neoplasms; Humans; Infusions, Parenteral; Jaw Neoplasms; Laryngeal Neoplasms; Leucovorin; Leukopenia; Male; Methotrexate; Middle Aged; Mouth Neoplasms; Neoplasm Metastasis; Neoplasms; Paranasal Sinus Neoplasms; Pharyngeal Neoplasms; Salivary Glands; Thrombocytopenia; Tongue Neoplasms; Tonsillar Neoplasms

Topics: Animals; Antimalarials; Antineoplastic Agents; Biguanides; Boron Compounds; Carcinoma, Ehrlich Tumor; Dogs; Folic Acid Antagonists; Hematopoiesis; Leucovorin; Leukopenia; Mice; Rabbits; Rats; Sarcoma 180; Species Specificity