International perspectives on treating advanced renal cell carcinoma

Molecular targeted therapies have revolutionized the treatment of metastatic renal cell carcinoma and significantly improved the overall survival. Currently seven molecular-target drugs; four tyrosine kinase inhibitors (sorafenib, sunitinib, pazopanib, and axitinib), two mTOR inhibitors (temsirolimus and everolims) and one anti-vascular endothelial growth factor monoclonal antibody (bevacizumab) have been available in the United States1 while six drugs except for bevacizumab in Japan. In cytokine era, the recommended dose of IL-2 in Japan, 0.7 to 2.1 million units per day based on the Japanese phase 2 clinical trial, were markedly lower than the standard dose in the United States because of less tolerance of cytokine agents in race difference.2 On the other hand, these six new drugs have the same recommended dose and indications as in the United States. This study by Ninomiya et al³ showed the importance of relative dose intensity (RDI) on targeted anticancer agents, especially sunitinib, and furthermore aggressive management of adverse events helped to maintain RDI that contributed to prolong the overall survival.