Purpose: Treatments for refractory metastatic renal cell cancer (RCC) are limited. Oral lenalidomide, a thalidomide-based drug having enhanced immunomodulatory and antiangiogenic properties and reduced toxicity, was evaluated for safety and efficacy in this setting.
Methods: In an open-label, single-center phase II trial, adults (> or =18 years old) with newly diagnosed RCC seen at our institution between December 2003 and April 2004 were recruited to receive at least three 28-day cycles (21 days on drug and 7 days off) of oral lenalidomide (25 mg/d). The dose was reduced as needed in cases of toxicity. The primary endpoint was tumor response rate. Secondary endpoints were time to tumor progression, response duration, 6-month and 12-month progression-free survival, overall survival, and safety.
Results: Thirty-nine of 40 patients (97%) were evaluable for response. Many in the evaluable population [63 (38-73) years; male, 73% (29/39)]; Zubrod performance status < or =1, 97% (38/39) had the clear cell histotype [85% (33/39)], had undergone previous immunotherapy or chemotherapy [59% (23/39)]; and had > or =2 metastatic sites [69% (27/39)]. Most [92% (36/39)] completed at least 3 treatment cycles (12 weeks). A complete response was observed in 1 patient (3%), partial response in 3 (8%), stable disease in 21 (53%), and progressive or unknown-status disease in 15 (38%). Time to tumor progression was < or =6 months in 24 patients (62%), 6 to 12 months in 6 (15%), and >12 months in 9 (23%). Median response duration was 6 (2-22) months and median overall survival was 17 months (0.80-39.6). The most common treatment-related adverse event was grade < or =2 fatigue [60% (24/40)]. The most common laboratory abnormalities were grade > or =3 neutropenia [50% (20/40)] and thrombocytopenia [28% (11/40)].
Conclusion: Lenalidomide is a safe and effective therapy for refractory metastatic RCC. Further studies of lenalidomide in this setting are warranted.