title: Double modulation of 5-fluorouracil by leucovorin and low-dose methotrexate in advanced colorectal cancer.
abstract: A phase II study was carried out to evaluate the efficacy and toxicity of a double biochemical modulation of 5-fluorouracil (5-FU) by methotrexate (MTX) and leucovorin (LV) in patients with advanced unresectable colorectal cancer. Forty-two patients with measurable metastases of colorectal cancer were treated with 5-FU in daily doses of 600 mg/m2 given in a 6-hour intravenous (i.v.) infusion on days 1-5, LV 50 mg/m2 i.v. on days 2,3 and 5, and MTX 40 mg/m2 i.v. on days 1 and 4, every 4 weeks. Twenty-eight patients had a single metastatic site, eleven double, whereas three had more than two metastatic sites. Objective response (one complete response) was observed in 12 of 40 patients (30%) (95% confidence interval 16-48), stable disease in 19 patients (47%) and progression in 9 patients (23%). Overall median survival was 12 months. Median time to progression was 6 months. Treatment was generally well tolerated. The most frequent adverse reactions were stomatitis (38%), nausea and vomiting (35%), diarrhea (31%), leukopenia (18%), and plantar-palmar erythroderma (15%). The combination of 5-FU, LV and MTX seems to be an active regimen in advanced colorectal cancer.
authors.affiliation: Department of Medical Oncology, Institute of Oncology, Ljubljana, Slovenia. borut.stabuc@kclj.si
authors.forename: B
authors.initials: B
authors.lastname: Stabuc
authors.forename: A
authors.initials: A
authors.lastname: Markovic
authors.forename: A
authors.initials: A
authors.lastname: Plesnicar
authors.forename: T E
authors.initials: TE
authors.lastname: Cizej
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016019:Survival Analysis
chemical_list: D002955:Leucovorin; D005472:Fluorouracil; D008727:Methotrexate