Phase II Trial of PS-341 in Patients With Renal Cell Cancer: A University of Chicago Phase II Consortium Study

Purpose Determine response rate, time to disease progression, and toxicity of the proteasome inhibitor PS-341 in patients with stage IV renal cell cancer. Patients and Methods PS-341 1.5 mg/m2 was administered intravenously twice weekly for 2 weeks every 21 days. Dose escalation to 1.7 mg/m2 ensued in the absence of grade 3 to 4 toxicities. Re-evaluation took place after three cycles. To assess proteasome inhibition, patients were randomly assigned to tumor core biopsy either before the first dose or after the third cycle of PS-341. Additionally, whole blood was collected at the same time intervals. Results Twenty-three patients were enrolled; 21 were assessable for response. Two patients were never treated (one patient refused treatment and one had insufficient tumor for biopsy). Eighteen patients completed at least three cycles of therapy; three patients experienced disease progression after two cycles. Grade 4 toxicities were arthralgia, diarrhea, and vomiting. Grade 3 toxicities included thrombocytope...