AN EASTERN-COOPERATIVE-ONCOLOGY-GROUP PHASE-II TRIAL OF TRIMETREXATE IN THE TREATMENT OF ADVANCED UROTHELIAL CARCINOMA

Background. Trimetrexate is an antifol that differs from methotrexate in ways that may be clinically important. Because methotrexate has act ivity in advanced bladder cancer, this trial was initiated. Methods. A mbulatory patients with advanced urothelial carcinoma were treated wit h the nonclassic antifol trimetrexate at the intravenous dose of 8 mg/ m(2) daily for 5 consecutive days every 3 weeks (4 mg/m(2) daily for 5 consecutive days for patients with creatinine levels greater than 1.6 mg/dl). Results. Of the 48 patients in the study, one had a complete response and seven had partial responses, for an overall response rate of 17% (exact 95% confidence interval, 7-30%). The response rate in p atients who had received prior methotrexate was 18%, suggesting lack o f complete cross-resistance. Toxicity was manageable and primarily muc osal, gastrointestinal, and myelosuppressive. Conclusions. Trimetrexat e has as much activity as other single agents in advanced urothelial c arcinoma. Combination therapy, possibly with cisplatin, platinum analo gs, or other antifols, using trimetrexate should be studied.