title: 5-methyltetrahydrofolate or 5-formyltetrahydrofolic acid to modulate 5-fluorouracil's cytotoxic activity in vivo. A phase II study in patients with advanced colon cancer.
abstract: The purpose of this study was to test the hypothesis that 5-methyltetrahydrofolate (Me-THF), a source of reduced folates alternative to leucovorin, could effectively modulate 5-fluorouracil's (5-FU) cytotoxic activity in patients with advanced colon cancer. A total of 23 patients were enrolled in a phase 11 trial; they received 5-FU as a 30-min infusion at a dose of 370 mg/m2 following a rapid i.v. push of 200 mg/m2 Me-THF, both drugs being given for 5 consecutive days. Cycles were repeated every 4 weeks until disease progression. No patient achieved a complete response. In all, 4 patients showed a partial response (17.4%), 7 developed stable disease (30.4%), and the remaining 12 (52.2%) progressed. Toxicity was acceptable and never exceeded WHO grade III intensity. According to our experience, the MeTHF/5-FU combination does not appear to be an effective treatment for advanced colon cancer. Despite its low toxic profile, in our opinion its wider use should be discouraged.
authors.affiliation: Isituto di Terapia Medica, Universitá degli Studi di Pavia, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Porta
authors.forename: M
authors.initials: M
authors.lastname: Moroni
authors.forename: O
authors.initials: O
authors.lastname: Epis
authors.forename: G
authors.initials: G
authors.lastname: Nastasi
mesh_terms: D000328:Adult; D000368:Aged; D000931:Antidotes / Q000494:pharmacology*; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols; D016923:Cell Death / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects*; D006801:Humans; D002955:Leucovorin / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D013763:Tetrahydrofolates / Q000494:pharmacology*
chemical_list: D000931:Antidotes; D000964:Antimetabolites, Antineoplastic; D013763:Tetrahydrofolates; D002955:Leucovorin; C005984:5-methyltetrahydrofolate; D005472:Fluorouracil