Pazopanib for the treatment of renal cancer.

INTRODUCTION

Dramatic advances in the care of patients with advanced renal cell carcinoma (RCC) have occurred over the last 10 years. Insights into the molecular pathogenesis of this disease have elucidated the importance of signaling cascades related to angiogenesis in the management of RCC. Pazopanib is a novel, small-molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptors (VEGFR)-1, -2, and -3; platelet-derived growth factor receptors (PDGFR)-α and -β; and c-kit tyrosine kinases. Pazopanib exhibits distinct pharmacokinetic and toxicity profiles compared with other agents in the class of VEGF signaling pathway inhibitors.

AREAS COVERED

This review discusses the scientific rationale for the development of pazopanib, as well as the preclinical and clinical trials that led to the approval of pazopanib for patients with advanced RCC. The most recent information, including data from the 2010 meeting of the American Society of Clinical Oncology and the design of ongoing Phase III trials, is discussed. Finally, an algorithm utilizing level I evidence for the treatment of patients with this disease is proposed.

EXPERT OPINION

The treatment of metastatic RCC has changed dramatically over the last 5 years. Six novel agents - sunitinib, sorafenib, temsirolimus, everolimus, bevacizumab (used in combination with interferon), and pazopanib (Votrient) - have been approved for the treatment of metastatic RCC. The clinical data to date clearly place pazopanib among the most active of the targeted therapies.