A phase II study of PS-341 (Bortezomib) in advanced or metastatic urothelial cancer. A trial of the Princess Margaret Hospital and University of Chicago phase II consortia.

Background: Based on evidence of activity in epithelial tumors in preclinical and Phase I studies, its novel mechanism of action, and its tolerability we undertook a study of bortezomib [PS-341], a reversible proteasome inhibitor, for patients with advanced or metastatic urothelial cancer.

Patients And Methods: Patients with advanced or metastatic unresectable urothelial carcinoma were enrolled onto this multicenter, phase II trial. Patients with measurable disease were treated with bortezomib 1.3 mg/m2/day (twice weekly for 2 weeks out of 3) by intravenous infusion on days 1, 4, 8, and 11 every 21 days. A two stage phase II design was used.

Results: Twenty-one patients were enrolled and twenty were eligible and received treatment. Eighty-five percent of patients had previous chemotherapy regimens. No objective responses were observed, median time-to-progression was 8.1 weeks (95% confidence interval [CI] 6.4 to 9), and median overall survival is estimated to be 15 weeks (95% CI 3.6 - NA). A total of 15 patients experienced a grade 3-4 adverse event. The most common were alkaline phosphatase (20% patients), lymphopenia (20% patients), myalgia (15% patients), dyspnea (15% patients) and thrombosis/embolism (15% patients).

Conclusion: Single-agent bortezomib is an ineffective treatment for progressive-cisplatin-refractory urothelial carcinoma and should not be considered for future clinical trials in this population of patients.