A randomized trial of two schedules of trimetrexate versus 5-fluorouracil in advanced colorectal cancer: a Southwest Oncology Group Study

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/m(2) i.v.q 2 weeks, TMQ at 12mg/m(2) i.v. weekly. Overall response rates were: 6% (four partial responses in 71 patients, 95% Cl of 2-14% for q 2 week TMQ, O% (zero of 29, 95% Cl of 0-29% for daily x 5 TMQ and 18% (two complete and nine partial responses in 62 patients, 95% Cl or 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 less than or equal to 3 toxicities were significantly more common with TMQ. TMQ does not appear to have significant anti-tumor activity against colorectal cancer.