Guru Sonpavde1, Thomas E Hutson, Cora N Sternberg. 1. Genitourinary Oncology Program, Texas Oncology, PA, US Oncology Research, 501 Medical Center Blvd, Webster, TX 77598, USA. guru.sonpavde@usoncology.com
Abstract
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.
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.
Authors: Elisabeth I Heath; Jeffrey Infante; Lionel D Lewis; Thehang Luu; Joe Stephenson; Antoinette R Tan; Saifuddin Kasubhai; Patricia LoRusso; Bo Ma; A Benjamin Suttle; Joseph F Kleha; Howard A Ball; Mohammed M Dar Journal: Cancer Chemother Pharmacol Date: 2013-01-24 Impact factor: 3.333