Phase II Study to Investigate the Efficacy, Safety, and Pharmacokinetics of Sorafenib in Japanese Patients with Advanced Renal Cell Carcinoma

AbstractObjective Sorafenib (Nexavar®) is an oral multi-kinase inhibitor that targets tumor growth and angiogenesis. This phase II study investigated efficacy, safety, and pharmacokinetics of sorafenib in Japanese patients with advanced renal cell carcinoma (RCC). Methods Nonrandomized, open-label study in Japanese patients with metastatic renal cell carcinoma who had received nephrectomy and failed ≥1 cytokine-containing therapy. The primary endpoint was response rate. Patients received sorafenib 400 mg twice daily (b.i.d.) on a continuous dosing schedule. Results A total of 129 patients (median age 63 years) were valid for intention-to-treat analyses. Confirmed partial responses were observed in 16 (12.4%) patients, and investigators assessed that 19 (14.7%) of the patients achieved a partial response. Stable disease was reported in 93 (72.1%) patients, and 103 (80.5%) patients had tumor shrinkage. Median progression-free survival was 224 days and the 25th percentile of overall survival was estimated at 288 days. The most frequently occurring drug-related adverse events (any grade) were elevated lipase (56%), hand–foot skin reaction (55%), alopecia (39%), increased amylase (38%), rash/desquamation (37%), and diarrhea (34%). A total of 14 (10.7%) patients had serious sorafenib-related adverse events, including one adverse event of worst grade 5 (dyspnea occurred 35 days after the last dose of study medication). The Ctrough,steady state values in RCC patients (n = 63) receiving sorafenib 400 mg b.i.d. were similar to those obtained from a Japanese phase I study involving patients with mixed solid tumors. Conclusion Sorafenib showed encouraging efficacy and was well tolerated in Japanese patients with metastatic RCC.