Drug review: Pazopanib

Abstract

Pazopanib (Votrient®) is an oral small-molecule multi-kinase inhibitor that primarily inhibits vascular endothelial growth factor receptor-1, -2 and -3, platelet endothelial growth factor receptor-α, and -β, and the stem-cell factor receptor c-kit. In preliminary experiments using angiogenesis models with mice and rabbits, pazopanib inhibited angiogenesis caused by combined vascular endothelial growth factor and basic fibroblast growth factor. Although pazopanib was developed as a therapeutic agent against various tumors, it is currently approved in many countries for advanced soft-tissue sarcoma and renal cell carcinoma. The importance of pazopanib has been acknowledged, with positive results demonstrated in large-scale clinical trials involving patients with softtissue sarcoma and renal cell carcinoma. However, adverse events such as liver dysfunction and hypertension are common, often necessitating treatment discontinuation. These adverse events are generally manageable, and from the perspective of health-related quality of life and costeffectiveness, pazopanib provides an improvement in quality-adjusted life years and decreases the treatment cost compared with other alternatives. In this review, we present the results of clinical trials and discuss the pharmacological action of pazopanib, with the aim of evaluating its current state by examining various associated issues.