The Food and Drug Administration (FDA) has approved sorafenib (Nexavar) for the treatment of advanced renal cell carcinoma. According to the drug's manufacturer, Bayer HealthCare AG, it is the first new drug approved for this indication in more than a decade.

The approval was based on the results of two clinical trials in which progression-free survival was significantly improved with sorafenib compared with placebo. According to the FDA, in the larger of the two phase III trials, most patients had previously received treatment with interleukin-2 or interferon. In that trial, median time to tumor progression or death in patients treated with sorafenib was 167 days compared with 84 days in patients who received placebo.

In preclinical studies, sorafenib was shown to inhibit multiple targets associated with tumor angiogenesis, including RAF kinase, VEGFR-2, VEGFR-3, PDGFR-ß, KIT, and FLT-3. The role that inhibition of a specific target plays in sorafenib's clinical activity, however, remains to be determined, explains Dr. Alison Martin, head of Genitourinary Therapeutics in NCI's CTEP.

Through a clinical trials agreement, NCI and Bayer are cosponsoring a phase III trial testing sorafenib in patients with unresectable, locally advanced, or stage IV melanoma, as well as numerous phase II trials exploring its activity in a broader range of advanced tumor types. A variety of other phase II studies currently open or planned for advanced kidney cancer will test whether adding targeted agents to sorafenib will improve its activity.

There is currently no known effective adjuvant therapy for patients with localized kidney cancer - that is, those who undergo resection but are at risk for relapse. Another oral multitargeted kinase inhibitor, sunitinib, has demonstrated early promising activity in advanced renal cancer, Dr. Martin says. Both sorafenib and sunitinib will be tested alone versus placebo in a large, three-arm, randomized trial of adjuvant therapy conducted by NCI-sponsored cooperative groups, led by the Eastern Cooperative Oncology Group, and in collaboration with Bayer and Pfizer. The trial is slated to open in the first quarter of 2006.