Pazopanib: a multikinase inhibitor with activity in advanced renal cell carcinoma.
Treatment options for patients with metastatic renal cell carcinoma (RCC) have changed dramatically, and a new paradigm has evolved. IFN-alpha and IL-2 were previously mainstays of therapy, but since December 2005, six new agents have been approved in the USA for the treatment of advanced RCC. Three of these new agents are multitargeted kinase inhibitors, including sunitinib, sorafenib, and recently pazopanib, two target the mTOR (temsirolimus and everolimus), and one is a humanized monoclonal antibody (bevacizumab in combination with IFN-alpha) that targets VEGF. Sunitinib has emerged as the standard of care for treatment-naive RCC patients, with the recently approved bevacizumab and IFN-alpha combination providing an additional option for this population. The recent approval of pazopanib, based on the results from sequential Phase II and III clinical trials demonstrating improved overall response rates and progression-free survival, provides yet another option for front-line therapy. The current article examines the pazopanib preclinical and clinical data, provides an overview of the development of this tyrosine kinase inhibitor, and provides some speculation concerning its role in RCC therapy.
Bukowski
Ronald M
RM
Cleveland Clinic Taussig Cancer Center, Professor of Medicine, CCF Lerner College of Medicine of CWRU, 28099, OH, USA. bukow464@sbcglobal.net
D000818:Animals; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000201:enzymology*; D002986:Clinical Trials as Topic; D006801:Humans; D007191:Indazoles; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
D007191:Indazoles; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; C516667:pazopanib; D017479:Receptors, Platelet-Derived Growth Factor; D040262:Receptors, Vascular Endothelial Growth Factor