Motzer RJ et al. (2007) Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 356: 115–124

Patients with metastatic renal cell carcinoma (RCC) have low rates of response (5–20%) to first-line therapy with interleukin 2 or interferon α; median overall survival is approximately 12 months. The multityrosine kinase inhibitor sunitinib malate targets the overexpression of vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) that occurs in many cases of RCC through inactivation of the VHL gene, and has shown promise in cytokine-resistant patients. Data from a phase III trial provide further evidence that angiogenic inhibition is promising as a treatment strategy for clear-cell RCC.

Motzer et al. randomized 750 patients with metastatic clear-cell RCC to first-line treatment with sunitinib (50 mg orally once daily for 4 weeks, then 2 weeks without treatment, in 6-week cycles) or interferon α (titrated to 9 MU subcutaneously 3 times a week). Patients in the sunitinib group had significantly longer median progression-free survival than those on interferon α (11 vs 5 months; P <0.001). Sunitinib also resulted in a significantly increased objective response rate (31% vs 6%; P <0.001). Symptoms including diarrhea and grade 3 or 4 neutropenia were more frequently reported in the sunitinib group, but patients on this treatment reported a significantly better quality of life than did patients on interferon α (P <0.001), and most adverse events resolved upon dose interruption or modification. Long-term data are needed to clarify issues such as the role of angiogenic growth factors in metastatic RCC, and the relative survival benefits of sunitinib and interleukin 2.