Phase II study of the safety and efficacy of temsirolimus in East Asian patients with advanced renal cell carcinoma.

Temsirolimus, an inhibitor of the mammalian target of rapamycin, is approved for treatment of patients with advanced renal cell carcinoma in the USA and Europe. Temsirolimus was not yet evaluated in East Asian patients. This non-randomized Phase II study enrolled 82 patients with advanced renal cell carcinoma [20 (24) Japanese, 30 (37) Korean and 32 (39) Chinese patients; median age (range): 55 (2683) years]. Most (71) received prior systemic therapy for metastatic disease; two-thirds were intermediate risk. Six Japanese patients received intravenous temsirolimus 20 mg/m(2) weekly for tolerability assessment (Group A); the remaining 76 received a 25 mg flat dose weekly (Group B). Temsirolimus was dosed once weekly. Primary efficacy end point was the Response Evaluation Criteria in Solid Tumors-defined clinical benefit rate in the intent-to-treat population. In the entire population, regardless of treatment group, the clinical benefit rate was 48 (95 confidence interval: 36, 59). Objective response rate was 11 (95 confidence interval: 5, 20), median progression-free survival was 7.3 months (95 confidence interval: 4.0, 9.2) and median time to treatment failure was 5.4 months (95 confidence interval: 3.5, 7.4). No patient in Group A demonstrated dose-limiting toxicity. The most frequent Grade 3 or 4 drug-related adverse events were anemia, hyperglycemia, hypophosphatemia and stomatitis (5 each). Serious adverse events reported in epsilon 5 of patients were pneumonia (9) and interstitial lung disease (7). Temsirolimus and its major metabolite, sirolimus, were long-lived throughout the dosage interval, with no evidence of accumulation. Temsirolimus was well tolerated and showed promising activity in Japanese, Korean and Chinese patients with advanced renal cell carcinoma.