Phase II trial of thalidomide for patients with advanced renal cell carcinoma.

PURPOSE: To assess efficacy and toxicity of thalidomide in patients with advanced renal cell carcinoma (RCC). PATIENTS AND METHODS: Twenty-six patients with RCC were treated with thalidomide at a starting dose of 200 mg daily. Thalidomide was increased by 200 mg every 2 weeks until a maximum dose of 800 mg or prohibitive toxicity was reached. Fifteen patients had prior nephrectomy, 11 patients had no prior systemic therapy, and 15 had received one prior systemic regimen. RESULTS: A maximum dose of 800 mg, 600 mg, 400 mg, and 200 mg was reached in five, 10, eight, and three patients, respectively. Grade 2 and 3 dyspnea occurred in four and three patients, respectively. Grade 2 and 3 neurologic toxicity was observed in five and two patients, respectively. Of the 25 assessable patients, the best response was stable disease in 16 (95% confidence interval [CI], 43% to 82%) patients. The 6-month progression-free survival rate was 32% (95% CI, 14% to 50%). Three patients achieved prolonged stable disease of 16, 16+, and 18+ months, including two patients who were refractory to previous cytokine therapy. Fifty-seven percent were alive at 1 year (95% CI, 37% to 76%). CONCLUSION: This trial does not support the routine use of thalidomide to induce partial response for metastatic RCC. Because disease stabilization occurs as a part of the natural history of metastatic RCC, the potential effect of thalidomide on progression-free and overall survival for patients with advanced RCC is being addressed in a randomized phase III trial. New immunomodulatory analogs of thalidomide that have shown potentially greater antitumor effects in preclinical models warrant study in metastatic RCC.