New York-Management of metastatic, clear-cell renal cell carcinoma has been significantly advanced by the development of the oral small-molecule kinase inhibitors sunitinib malate (Sutent) and sorafenib (Nexavar), recent results from two large, international, randomized, double-blind, phase III trials indicate. Both studies appeared in the Jan. 11, 2007 issue of the New England Journal of Medicine (2007; 356:115-24 and 125-34).
Sunitinib was investigated as a first-line treatment for metastatic RCC in a study that randomized 750 treatment-naïve patients 1:1 to oral sunitinib or subcutaneous interferon alfa-2a (Roferon-A). Enrolled patients had Eastern Cooperative Oncology Group performance status 0 or 1 and a clear-cell histologic component. Sunitinib was administered at a dose of 50 mg once daily in 6-week cycles (4 weeks on, 2 weeks off). Interferon alfa-2a was administered three times weekly at doses of 3 MU for the first week, 6 MU in the second week, and 9 MU thereafter. Dose adjustments of both treatments were allowed for adverse-event management.
"The superiority of sunitinib was very impressive, and greater than expected. While the study was designed anticipating about a 30% increase in progression-free survival, the effect of sunitinib exceeded 200%. As a result, it is time for a paradigm shift away from the cytokines to use of sunitinib as the new standard treatment for metastatic, clear-cell RCC," he told Urology Times.
"One of the most important aspects of those analyses was the finding that sunitinib had significant benefit even in the MSKCC favorable-risk group, who are considered to be the ideal candidates for cytokine therapy," Dr. Motzer said.
Second-line efficacy shown
In the second study, researchers from the Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET) randomized 903 patients with metastatic, clear-cell RCC resistant to standard cytokine therapy 1:1 to treatment with sorafenib or placebo. Patients were stratified by country and MSKCC prognostic score prior to randomization. Sorafenib was administered at a dose of 400 mg twice daily in 6-week cycles for four cycles, then switched to 8-week cycles. Dosage was reduced or treatment delayed as indicated for adverse event management.