CALGB 90207: Phase II trial of bortezomib in patients with previously treated advanced urothelial tract transitional cell carcinoma (TCC).

4582 Background: No standard 2(nd)-line chemotherapy exists for metastatic TCC. Response rates to 2(nd)-line chemotherapy for advanced TCC are low and response duration tends to be short. Bortezomib is a proteasome inhibitor with preclinical activity against TCC. METHODS: Twenty-five patients with advanced TCC who had been previously treated with combination chemotherapy were enrolled in a multi-institutional single-arm trial from December 2003 through April 2005. Treatment consisted of bortezomib 1.3 mg/m(2) intravenously twice weekly for two consecutive weeks, followed by a 1-week rest period. The primary endpoint was objective response rate by RECIST criteria. Secondary endpoints included safety, toxicity, progression-free survival, and overall survival. RESULTS: The median age was 65.5 yrs (59-7-74.9) and the median number of years since diagnosis was 1.4 (0.9-3.6). 72% of patients were male. 65% of patients had visceral metastases, and 20% of patients had lymph node-only metastases. Prior chemotherapy regimens included gemcitabine/cisplatin (50%), gemcitabine/carboplatin (25%), paclitaxel/carboplatin (5%), single agent paclitaxel (5%), and other multi-agent regimens (15%). Median hemoglobin was 11.4 g/dL (inter-quartile range 10.6-12.3). No objective responses were observed. The median time to progression was 2.1 months (95% CI= 1.4-5.5). Median overall survival was 5.5 months (95% CI= 3.6-8.1). Toxicity was modest. Grade 3/4 drug-related toxicities included thrombocytopenia (6%), sensory neuropathy (6%), hyperglycemia (6%), neuropathic pain (6%), dehydration (6%) and vomiting (6%). There were no treatment-related deaths. CONCLUSIONS: Although bortezomib is well tolerated in patients with previously treated advanced TCC, it does not have anti-tumor activity as 2nd-line therapy in TCC. No significant financial relationships to disclose.

Duke Scholars

Author Susan Halabi Biostatistics & Bioinformatics, Division of Biostatistics