Piritrexim in Advanced, Refractory Carcinoma of the Urothelium (E3896): A Phase II Trial of the Eastern Cooperative Oncology Group

This was a single-agent phase II clinicaltrial of the antifol piritrexim in patientswith advanced transitional cell carcinomaof the bladder. Methods: Patientswith previously-treated, advancedurothelial carcinoma were treated with oralpiritrexim at a dose of 25 mg three timesdaily for 5 consecutive days each week for3 consecutive weeks followed by a 1-weekrest period. Courses were repeated every28 days. Results: Thirty-fivepatients were enrolled in the study, with28 patients evaluable for survival andtoxicity and 27 evaluable for response. Toxicity: Myelosuppression was themajor dose-limiting toxicity, with WHOgrade 3/4 thrombocytopenia in 4 patients,granulocytopenia in 1 patient, and anemiain 3 patients. Grade 3 nonhematologictoxicity consisted of neuropathy in 5patients, hepatotoxicity in 2, nausea in 2,and 1 each with pulmonary toxicity andrash. Efficacy: Of the 27 patientsevaluable for response, 2 (7%) achieved anobjective response, lasting 112 and 142days, respectively. Conclusion: Piritrexim has minimal activity in patientswith previously treated transitional cellcarcinoma of the bladder, regardless ofprior exposure to methotrexate, and furtherevaluation of this compound in thisclinical setting is not warranted.