title: Double modulation of 5-fluorouracil by methotrexate and high-dose L-leucovorin in advanced colorectal cancer.
abstract: A phase II trial was performed to evaluate the efficacy and toxicity of a double modulation of 5-fluorouracil (5-FU) by methotrexate (MTX) and L-leucovorin (L-LV) in patients with advanced recurrent (inoperable) or metastatic colorectal carcinoma (ACC). Between July 1993 and October 1995, 41 patients with ACC received a regimen that consisted of MTX 150 mg/m2 i.v., infused over a 20-minute period at hour 0, followed 19 hours later by L-LV 250 mg/m2 in a 2-hour i.v. infusion. 5-FU, 900 mg/m2, was administered by i.v. push injection at hour 20. Beginning 24 hours after MTX administration, all patients received four doses of L-LV, 15 mg/m2 i.m., every 6 hours. Cycles were repeated every 15 days. Two patients were not assessable for response. Objective regression was observed in 11 of 39 (28%) patients, [95% confidence interval (CI), 14-42%]. One (2%) patient achieved complete response (CR) and 10 (26%) partial response (PR). No change was recorded in 15 (39%) patients and progressive disease was noted in 13 (33%) patients. The median time to treatment failure was 6 months and the median survival time was 10 months. Toxicity was within acceptable limits, but one therapy-related death due to severe leukopenia was observed. The dose-limiting toxicity was mucositis. Eight episodes of grade 3 or 4 stomatitis were observed, and were responsible for dosage modifications of MTX and 5-FU. In conclusion, further in experimental and clinical studies are clearly necessary in order to design the best modulatory strategy of 5-FU.
authors.affiliation: Grupo Oncológico Cooperativo del Sur, Neuquén, República Argentina.
authors.forename: A O
authors.initials: AO
authors.lastname: Romero
authors.forename: J E
authors.initials: JE
authors.lastname: Perez
authors.forename: M A
authors.initials: MA
authors.lastname: Cuevas
authors.forename: J A
authors.initials: JA
authors.lastname: Lacava
authors.forename: C L
authors.initials: CL
authors.lastname: Sabatini
authors.forename: M E
authors.initials: ME
authors.lastname: Dominguez
authors.forename: R
authors.initials: R
authors.lastname: Rodriguez
authors.forename: M R
authors.initials: MR
authors.lastname: Barbieri
authors.forename: E H
authors.initials: EH
authors.lastname: Ortiz
authors.forename: M A
authors.initials: MA
authors.lastname: Salvadori
authors.forename: L A
authors.initials: LA
authors.lastname: Acuña
authors.forename: J M
authors.initials: JM
authors.lastname: Acuña
authors.forename: M J
authors.initials: MJ
authors.lastname: Langhi
authors.forename: S
authors.initials: S
authors.lastname: Amato
authors.forename: M R
authors.initials: MR
authors.lastname: Machiavelli
authors.forename: B A
authors.initials: BA
authors.lastname: Leone
authors.forename: C T
authors.initials: CT
authors.lastname: Vallejo
authors.forename: V
authors.initials: V
authors.lastname: Lorusso
authors.forename: M
authors.initials: M
authors.lastname: DeLena
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009367:Neoplasm Staging; D016019:Survival Analysis
chemical_list: D002955:Leucovorin; D005472:Fluorouracil; D008727:Methotrexate