Pazopanib, a potent orally administered small-molecule multitargeted tyrosine kinase inhibitor for renal cell carcinoma

Guru Sonpavde, Thomas E Hutson, Cora N Sternberg
Expert Opinion on Investigational Drugs 2008, 17 (2): 253-61

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.

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