Clinical Medicine Reviews in Oncology

The treatment of patients with advanced renal cell carcinoma (RCC) has been revolutionized by the development of agents directed against vascular endothelial growth factor (VEGF) signaling. These agents, such as sorafenib and sunitinib, have been advocated as first-line treatments for RCC. However, responses to these agents are neither complete nor durable and nearly all patients will require second-line therapy. Everolimus (RAD001) is an oral inhibitor of mammalian target of rapamycin (mTOR) which has recently been shown to significantly prolong the progression free survival of patients with RCC who have failed either sorafenib or sunitinib (or both) as compared to placebo. Based on these results, everolimus was approved by the Food and Drug Administration (FDA) on March 30, 2009 and is now considered a standard therapeutic option for patients who have failed front-line VEGF-targeted therapy. Everolimus is now actively undergoing further evaluation in multiple clinical scenarios including sequential, combinational, and adjuvant therapy as well as in non-clear cell RCC.