Is there any role for thalidomide as a monotherapy in the management of metastatic renal cell carcinoma?

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Mar 8 2006

Thalidomide remains an enigma in the treatment of metastatic renal cell carcinoma (RCC). Initial clinical trials suggested a benefit, but more recently, subsequent randomized trials studying thalidomide in combination with other agents such as interferon have demonstrated no added benefit.

Two recent phase I/II trials demonstrate modest activity in combination with IL-2 but this observation awaits confirmation in a phase III setting. In this report by Lee and colleagues, thalidomide as a monotherapy is compared to medroxyprogesterone acetate (Megace). Of note, Megace was the first therapy approved for the treatment of RCC in the United States, but now is largely considered to have little activity against the disease and be more of a placebo.

Sixty patients were entered into this randomized phase II trial, with 48 patients evaluable for response. Patients received either Megace at a dose of 300mg per day (31 patients), or thalidomide, at doses starting at 100mg and increasing by 100mg every two weeks to a maximum dose of 400mg per day unless limited by toxicity (29 patients). All patients had either failed previous immunotherapy (87.1%) or were not suitable candidates for upfront immunotherapy (12.9%). In the thalidomide arm, there were no objective responses and only 3 patients demonstrated stable disease. All patients in the Megace arm progressed. There was no difference in overall survival between the two arms (8.2 months for thalidomide versus 4.8 months for Megace, p=0.62). Of note, only 30.8% of patients in the thalidomide arm were able to tolerate the maximum dose of 400mg per day.

Thalidomide as a monotherapy appears to have little activity and significant toxicity in the treatment of metastatic RCC and should be abandoned. The jury remains out on combinatorial therapy with thalidomide and other agents such as interleukin 2.

By Christopher G. Wood, MD

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