Application of thalidomide/interleukin-2 in immunochemotherapy-refractory metastatic renal cell carcinoma.

Thalidomide has been reported to yield anti-tumor activity in advanced renal cell carcinoma (RCC). We evaluated safety and efficacy of a combination therapy comprising interleukin (IL)-2 and thalidomide in patients with metastatic RCC refractory to both immuno- and chemotherapy. Twelve patients with progressive metastatic RCC who had failed prior treatment with immunochemotherapy and desired further active therapy were enrolled in this study. Oral thalidomide was started at 200 mg/day and escalated after 2 days to 400 mg/day at week 0. IL-2 at 7 MIU/m was given by s.c. injection, starting at week 1, days 1-5, weeks 1-4, with rest from IL-2 at weeks 5 and 6. Response was assessed every two therapy cycles. Ten patients were evaluable for response. There was no objective response; four patients showed stable disease for 14+, 11+, 10+ and 9 months, respectively. Toxicities were predominantly grade I-II, and included somnolence and constipation, as well as flu-like symptoms associated with IL-2. However, one patient developed serious constipation which led to a paralytic ileus and discontinuation of treatment. Another patient left the study after 7 weeks due to increasing disorientation/confusion. Eight patients required IL-2 dose reduction. Time on therapy ranged from 3 to 44 weeks (median 20 weeks). Median overall survival was 12+ months. At present, all patients have discontinued treatment. We conclude that outpatient administration of thalidomide/IL-2 is feasible in patients with heavily pretreated and progressive RCC who desire further active treatment. However, toxicity and costs are considerable, and clinical benefit is uncertain. Therefore, thalidomide/IL-2 might not represent a promising therapeutic approach for this subgroup of patients.