Effective options are lacking for progressive castration-refractory prostate cancer (CRPC) after conventional chemotherapy. Sunitinib is an orally administered multitargeted tyrosine kinase inhibitor that is approved multinationally for renal cell carcinoma and gastrointestinal stromal tumors. A phase II trial was conducted to examine the efficacy and toxicities of sunitinib in metastatic CRPC progressing after 1-2 previous chemotherapy regimens including docetaxel. The primary objective was clinical progression-free survival (PFS) with a 12-week PFS > or = 30% assumed to be of interest. Secondary objectives included prostate-specific antigen (PSA) response, modulation of PSA kinetics, objective response, quality of life, pain, survival, and toxicities. Sunitinib 50 mg daily was administered orally on days 1-28 of each 6-week cycle. Patients were treated to a maximum of 8 cycles or until clinically progressive disease or intolerable toxicity.