Pazopanib, a potent orally administered small-molecule multitargeted tyrosine kinase inhibitor for renal cell carcinoma.
BACKGROUND
The recent approvals of sunitinib, sorafenib and temsirolimus have revolutionized the management of renal cell carcinoma (RCC). Pazopanib (GW-786034) is a second-generation multitargeted tyrosine kinase inhibitor against VEGFR-1, 2 and 3, platelet-derived growth factor receptor (PDGFR)-alpha, PDGFR-beta and c-kit.


OBJECTIVE
Data supporting the development of pazopanib for RCC are reviewed.


METHODS
Preclinical and clinical data available for pazopanib are presented.


RESULTS
Preclinical evaluation has revealed excellent anti-angiogenic and anti-tumor activity in several mouse models. A Phase II clinical trial of pazopanib in untreated or cytokine/bevacizumab pretreated RCC has demonstrated promising activity accompanied by a favorable toxicity profile. A placebo-controlled Phase III trial is ongoing in untreated or cytokine-treated patients with RCC. Ongoing trials are further evaluating pazopanib in a variety of other malignancies.
Sonpavde
Guru
G
Genitourinary Oncology Program, Texas Oncology, PA, US Oncology Research, 501 Medical Center Blvd, Webster, TX 77598, USA. guru.sonpavde@usoncology.com
Hutson
Thomas E
TE
Sternberg
Cora N
CN
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D006801:Humans; D007191:Indazoles; D007680:Kidney Neoplasms / Q000188:drug therapy*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D013449:Sulfonamides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D007191:Indazoles; D011743:Pyrimidines; D013449:Sulfonamides; C516667:pazopanib; D011505:Protein-Tyrosine Kinases