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 activity in advanced bladder cancer, this trial was initiated.


METHODS
Ambulatory patients with advanced urothelial carcinoma were treated with the nonclassic antifol trimetrexate at the intravenous dose of 8 mg/m2 daily for 5 consecutive days every 3 weeks (4 mg/m2 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 patients who had received prior methotrexate was 18%, suggesting lack of complete cross-resistance. Toxicity was manageable and primarily mucosal, gastrointestinal, and myelosuppressive.


CONCLUSIONS
Trimetrexate has as much activity as other single agents in advanced urothelial carcinoma. Combination therapy, possibly with cisplatin, platinum analogs, or other antifols, using trimetrexate should be studied.
Witte
R S
RS
University of Wisconsin Comprehensive Cancer Center, Madison.
Elson
P
P
Khandakar
J
J
Trump
D L
DL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016597:Trimetrexate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
D016597:Trimetrexate