title: A randomized trial of two schedules of trimetrexate versus 5-fluorouracil in advanced colorectal cancer: a Southwest Oncology Group study.
abstract: Trimetrexate (TMQ), a non-classical folate antagonist, was studied in a randomized controlled trial in patients with advanced colorectal cancer and without prior chemotherapy. Patients were randomly assigned to one of three treatments: TMQ at 200 mg/m2 i.v. q 2 weeks, TMQ at 12 mg/m2 i.v. daily x 5 or 5-fluorouracil (5-FU) at 15 mg/kg i.v. weekly. Overall response rates were: 6% (four partial responses in 71 patients, 95% CI of 2-14%) for q 2 week TMQ, 0% (zero of 29, 95% CI of 0-29%) for daily x 5 TMQ and 18% (two complete and nine partial responses in 62 patients, 95% CI of 9-30%) for 5-FU. Median survival estimates were 10.3 months for the q 2 week TMQ schedule, 8.7 months for the daily x 5 TMQ schedule and 13.6 months for the 5-FU schedule. Grade < or = 3 toxicities were significantly more common with TMQ. TMQ does not appear to have significant antitumor activity against colorectal cancer.
authors.affiliation: Norfolk Diagnostic Clinic, VA 23502, USA.
authors.forename: T D
authors.initials: TD
authors.lastname: Brown
authors.forename: T R
authors.initials: TR
authors.lastname: Fleming
authors.forename: P J
authors.initials: PJ
authors.lastname: Goodman
authors.forename: J S
authors.initials: JS
authors.lastname: Macdonald
authors.forename: R P
authors.initials: RP
authors.lastname: Pugh
authors.forename: T
authors.initials: T
authors.lastname: O'Rourke
mesh_terms: D000368:Aged; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016597:Trimetrexate / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D005472:Fluorouracil; D016597:Trimetrexate