A multi-targeted tyrosine kinase inhibitor of receptors for vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) shows significant anti-tumor effects in patients with metastatic renal cell carcinoma.
The drug may, for the first time, offer a second line treatment option for that malignancy, according to a multicenter team of researchers, led by Robert J. Motzer of Memorial Sloan-Kettering Cancer Center in New York City. Their study of SU11248 (sunitinib malate) is published in the January issue of the Journal of Clinical Oncology.A total of 63 patients with metastatic renal cell carcinoma progressing on first-line therapy were enrolled in a trial of SU11248, given as daily oral monotherapy in 6-week cycles of 4 weeks on and 2 weeks off. Of the total treated, 25 (40%) achieved a partial response with SU11248 and another 17 (27%) had stable disease lasting 3 months or more. Median time to disease progression for the group as a whole was 8.7 months. SU11248 was tolerated by most, with manageable toxicities. The researchers note that high-dose interleukin-2 and subcutaneous interferon-alfa “represent the near sum” of treatment options for renal cell carcinoma. These drugs have a 14% or lower complete or partial response rate.Dr. Motzer and colleagues speculate that the relatively high anti-tumor activity of SU11248 is attributable to its targeting of tumor vasculature, endothelial cells and pericytes. “There is little to be skeptical about in this report,” writes editorialist Dr. Nicholas J. Vogelzang, of the University of Nevada in Las Vegas. He points out that “the remarkable, well-documented and long-term responses are seen across multiple treatment centers” participating in the study. Dr. Vogelzang notes that there are a number of similar agents, in earlier phases of study, that are also showing activity against renal cell carcinoma, that are finally providing “‘an embarrassment of riches'” in treatment options.There is still much to be cautious about, he warns. The precise mechanism of action of SU11248 and how resistance to it develops is still unknown. Optimum dosing is also unknown and it may be that continuous administration is better than the four weeks on, two off cycle used in this study.But all in all, Dr. Vogelzang notes that the work by Dr. Motzer and colleagues represents a “breakthrough” in the treatment of metastatic renal cell carcinoma.(Source: J Clin Oncol 2006;24:1-2,16-24: Reuters Health: Oncolink: January 2006.)