Topotecan in previously treated advanced urothelial carcinoma: an ECOG phase II trial

Background: Chemotherapeutic agents are playing an increasing role in the management of urothelial carcinoma. Despite recent advances in the treatment of this disease there continues to be a need to identify new active agents and their toxicity spectra. Topotecan is an agent as yet unstudied in bladder cancer. Methods: Ambulatory patients with progressive advanced urothelial carcinoma following prior systemic chemotherapy were treated with topotecan 1.5 mg/m(2) intravenously (IV) daily for 5 days every three weeks for 6 cycles. Doses were modified for leukopenic fever, thrombocytopenic bleeding, and any grade 3 or 4 (NCI common toxicity criteria) toxicity. Results: Forty-four eligible patients entered the trial. There were 4 partial responses for an overall response rate of 9.1% (exact 95% two-stage binomial CI, 2.9% to 25.5%). Major identified toxicities were gastrointestinal and myelosuppression. There were no treatment-related deaths. Conclusions: Topotecan at this dose and schedule has minimal activity in previously treated patients with advanced urothelial carcinoma. Toxicities can be seven but are manageable.