Phase II study of bortezomib in patients with previously treated advanced urothelial tract transitional cell carcinoma: CALGB 90207

Abstract

BackgroundThere is no standard second-line treatment for advanced urothelial carcinoma (UC). Response rates to second-line chemotherapy for advanced UC are low and response duration is short. Bortezomib is a proteasome inhibitor with preclinical activity against UC. Patients and methodsTreatment consisted of bortezomib 1.3 mg/m2 i.v. twice weekly for two consecutive weeks, followed by a 1-week break. The primary end point was objective response rate (complete response+partial response) by Reponse Evaluation Criteria in Solid Tumors criteria. Secondary end points included safety, toxicity, and progression-free and overall survival. ResultsIn all, 25 patients with advanced UC previously treated with combination chemotherapy were enrolled in a multi-institutional single-arm trial from December 2003 through April 2005. Only 29% of patients had node-only metastases. Grade 3/4 drug-related toxic effects included thrombocytopenia (4%), anemia (8%), lymphopenia (8%), sensory neuropathy (6%), hyperglycemia (4%), hypernatremia (4%), fatigue (4%), neuropathic pain (6%), dehydration (4%), and vomiting (4%). No objective responses were observed [95% confidence interval (CI)=0–12]. The median time to progression was 1.4 months (95% CI=1.1–2.0 months), and the median survival time was 5.7 months (95% CI=3.6–8.4 months). There were no treatment-related deaths. ConclusionAlthough bortezomib is well tolerated, it does not have antitumor activity as second-line therapy in UC.