Phase II study of gemcitabine, cisplatin, and sunitinib (S) in patients with advanced urothelial carcinoma (UC).

Abstract

282 Background: Sunitinib (S) has single-agent activity in patients with advanced urothelial carcinoma (UC). Preclinical studies in UC demonstrate at least additive antitumor activity combining S with gemcitabine (G) or cisplatin (C). Methods: Patients with chemonaïve metastatic UC were enrolled in a multicenter phase II trial with overall response rate (ORR) as the primary endpoint. The initial dosing regimen, based on a phase I trial (Reck, 2010), was G 1000 mg/m 2 IV (Days 1 & 8), C 70 mg/m 2 IV (Day 1), and S 37.5 mg PO daily (Days 1-14)/each 21-day cycle (up to 6 cycles), followed by S 37.5 mg daily until progression. Results: From December 2008 to August 2009, 15 eligible patients enrolled. Seven of 15 patients discontinued treatment early (median: 3 cycles) due to toxicity, most often due to recurrent neutropenia and thrombocytopenia. Intrapatient dose reductions were required for G (12/15), C (8/15), and S (10/15). Eight of 15 patients experienced serious adverse events. Based on the toxicity profile, enrollment was held and the dosing regimen was revised to G 800 mg/m 2 IV (Days 1 and 8), C 60 mg/m 2 IV (Day 1), S 37.5 mg PO daily (Days 1-14). From December 2009 to April 2011, 18 additional patients were enrolled. Despite the reduced starting doses, intrapatient dose reductions were required for G (13/18), C (9/18), and S (15/18). The most frequent Grade 3-4 toxicities for both groups were neutropenia (70%), thrombocytopenia (58%), and anemia (30%). Antitumor activity is shown in the Table. Median PFS was 7.9 and median OS was 13.8 months. Conclusions: Combination G+C+S is poorly tolerated and results in activity comparable to historical results with G+C alone. Supported in part by a grant from Pfizer Inc. [Table: see text]