Phase 2 trial of epothilone B analog BMS-247550 (ixabepilone) in advanced carcinoma of the urothelium (E3800): a trial of the Eastern Cooperative Oncology Group.

<bold>Background: </bold>Paclitaxel and docetaxel are active agents in advanced urothelial cancer. BMS-247550 (ixabepilone) has activity in preclinical models in paclitaxel resistant models. A phase 2 trial of this epothilone was performed to determine the activity and toxicity of this agent in a multi-institutional setting in patients previously treated with 1 prior chemotherapy regimen.<bold>Methods: </bold>Forty-five patients with advanced urothelial carcinoma were treated with BMS-247550 40 mg/m(2) over 3 hours intravenously on Day 1 of a 21-day cycle and continued therapy until progression or unacceptable toxicity.<bold>Results: </bold>Five patients obtained an objective partial response (PR) among the 42 eligible patients for an overall response rate of 11.9% (90% confidence interval [5.3%, 26.5%]). Median overall survival of the group was 8 months. Toxicity was moderate with granulocytopenia, fatigue, and sensory neuropathy being the most common side effects noted.<bold>Conclusions: </bold>BMS-247550 (ixabepilone) has very modest activity as a second-line therapy for advanced urothelial cancer. Responses in visceral, nodal, and soft tissues sites were observed. Granulocytopenia without fever, fatigue, and sensory neuropathy was common. [ABSTRACT FROM AUTHOR]