WHAT'S HOT IN... MEDICINE , Mar./Apr. 2008

Most cases of kidney cancer are of the type known as renal-cell carcinoma. This is by no means the most common cancer, perhaps with no more than 40,000 new cases being diagnosed in the United States every year. However, once surgical management has done all it can, treatment options have been few and the results of them far from brilliant.

For metastatic renal-cell carcinoma, cytokine therapy with interleukin-2 or interferon alfa may be tried. Among newer drugs attracting attention are sunitinib (Sutent, SU11248) and sorafenib (Nevaxar, BAY-43-9006), and both are attaining citation prominence, the first drug being the subject of two clinical studies in the Top Ten (#5, #7) while the other one is waiting in the wings at #15 (B. Escudier, et al., New Engl. J. Med., 356[2], 125-34, 2007; latest bimonthly count 38).

Dr. Robert J. Motzer and colleagues (#5) summarize the biological rationale for trying tyrosine kinase inhibitors, and preclinical studies had suggested that sunitinib might have activity against both new vessel growth (angiogenesis) and tumor-cell proliferation. Theirs was a phase II (uncontrolled) clinical study in 63 patients with metastatic cancer in whom cytokine treatment had not been successful.

Encouragingly, 25 patients had a partial response to sunitinib and 17 others experienced stabilization of their disease. Toxicity, principally fatigue, was "manageable," though four patients did experience a decline in cardiac ejection fraction.

Almost exactly a year later in publication terms, Motzer et al. moved the sunitinib story on significantly. Paper #7 reports a phase III, randomized controlled trial comparing the new drug with interferon alfa in 750 cases, but this time the patients had not previously been given systemic therapy.

Progression-free survival was significantly longer in the sunitinib group than in the patients given interferon (median 11 months vs. 5 months). Declines in ejection fraction of any severity were recorded in 10 out of 375 patients in the sunitinib group and in 3 of 360 controls, but there were no clinical consequences of this.

The third paper (#15) is about sorafenib, which is a "multikinase inhibitor of tumor-cell proliferation and angiogenesis." In this randomized, placebo-controlled trial in 903 patients whose renal-cell carcinoma was resistant to standard therapy, the active drug was associated with increased progression-free survival.

Other drugs being explored in such patients and whose mode of action has a well-founded molecular basis include bevacizumab (recently shown in a phase III trial, again by Escudier and colleagues [Lancet, 370(9605): 2103-11, 2007] to significantly improve progression-free survival in comparison with interferon alfa-2a), axitinib, and temsirolimus.

One can certainly see why Dr. Nicholas J. Vogelzang, in his January, 2006, editorial linked to #5 (J. Clin. Oncol., 24[1]: 1-3, 2006), described the treatment options for metastatic renal carcinoma as "an embarrassment of riches." The field of runners will be trimmed down in time on the basis of comparative efficacy in head-to-head trials and of other factors such as cost and toxicity. One current concern with sunitinib is cardiac toxicity (T.F. Chu, et al., Lancet, 370[9604]: 2011-19, 2007; H. Joensuu, Lancet, 370[9604]: 1978-80), and patients given this drug may need regular checks on their cardiac function (e.g., by measurement of left-ventricular ejection fraction)."

A former deputy editor of The Lancet, Mr. David W. Sharp, M.A. (Cambridge), is a freelance writer living in Minchinhampton, U.K.