Closing in on treatments for kidney cancer

Two compounds, approved recently, provide long-awaited redress for renal cell carcinoma

At a glance

A celebrity who recently had a kidney tumor removed was Sean Connery. Fortunately for him, his tumor was benign. His case generated some awareness of the disease, which affects primarily white men in certain countries (see box).

The two new compounds-sorafenib (Nexavar, Bayer/ Onyx) and sunitinib (Sutent, Pfizer)-are inhibitors of tumor cell growth and angiogenesis; they target the same multiple receptors for the tyrosine kinases involved in these processes. But there are differences, too: Sorafenib targets Raf-kinase, vascular endothelial growth factor receptor (VEGFR), and platelet-derived growth factor receptor (PDGFR), while sunitinib focuses on VEGFR and PDGFR but not Raf-kinase. Researchers believe that all these pathways play significant roles-yet to be clarified-in advanced RCC.

"Sorafenib and sunitinib are part of a wave of new targeted therapies for various can-cers," stated Brad L. Stanford, Pharm.D., BCOP, assistant professor of pharmacy practice-oncology-at Texas Tech University Health Sciences Center's School of Pharmacy. "Although the two new drugs are similar, they also differ in important respects. The differences in mechanism of action appear to affect the toxicity profile, which is also dissimilar between the two agents. And, in turn, the dosing schedule is also significantly different...."

Due to its shorter half-life, sorafenib is dosed twice daily on a continuous basis, while sunitinib, with a long half-life, is dosed in a cyclical fashion of four weeks of treatment followed by two weeks off. The new agents were studied primarily for clear cell renal carcinoma-the most common histology of kidney cancer-seen in about 85% of cases.

However, one study, published in the Lancet in 2001, showed that radical nephrectomy performed in advance of cytokine therapy improved both survival and time to progression in advanced RCC patients.