Phase 2 trial of pemetrexed disodium and gemcitabine in advanced urothelial cancer (E4802): A trial of the Eastern Cooperative Oncology Group

BACKGROUND. There is a need to identify active new regimens in patients with advanced urothelial cancer. Pemetrexed and gemcitabine are active agents in advanced urothelial cancer. A phase 2 trial of the combination of these 2 agents was performed in patients with advanced urothelial cancer who were previously untreated for metastatic disease. METHODS. Forty-six patients with advanced urothelial carcinoma received pemetrexed disodium 500 mg/m² and gemcitabine 1000 mg/m² intravenously on Day 1, with gemcitabine repeated on Day 8. Cycles were repeated every 3 weeks for a maximum of 6 cycles. RESULTS. Two patients attained a complete response, and 12 patients attained a partial response for an overall response rate of 31.8% (90% confidence interval, 20.4%-45.2%). The median time to disease progression was 5.8 months, and the median overall survival was 13.4 months. Thirty-three patients (75%) experienced grade ≥3 neutropenia, and 5 patients (11%) had febrile neutropenia. There were 2 therapy-related deaths. CONCLUSIONS. The combination of pemetrexed and gemcitabine had moderate antitumor activity in previously untreated patients with advanced urothelial cancer at the expense of significant myelosuppression.