Axitinib in Metastatic Renal Cell Carcinoma
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REVIEW
Axitinib in Metastatic Renal Cell Carcinoma Kriti Mittal · Laura S. Wood · Brian I. Rini
To view enhanced content go to www.biologicstherapy-open.com Received: July 25, 2012 / Published online: October 16, 2012 © The Author(s) 2012. This article is published with open access at Springerlink.com
ABSTRACT Targeted agents have revolutionized the management of metastatic renal cell carcinoma (RCC). Axitinib, an inhibitor of vascular endothelial growth factor receptor (VEGFR), has been an important addition to currently available therapies for advanced RCC. Its ability to inhibit VEGFRs at nanomolar concentrations distinguishes it as a potent tyrosine kinase inhibitor, with increased selectivity for VEGFR-1, 2, and 3 at clinically applicable concentrations. The phase 3 AXIS trial has established its superiority in prolonging progression-free survival (PFS) in previously treated RCC patients (median PFS 6.7 months for axitinib vs. 4.7 months for sorafenib).
Common toxicities of axitinib include hypertension, diarrhea, nausea, hand-foot syndrome, fatigue, and hypothyroidism. Axitinib-induced diastolic blood pressure elevation may be associated with improved clinical outcome, likely reflecting the “on-target” effect of axitinib. Dose escalation to achieve therapeutic plasma drug levels is of considerable clinical interest. Although axitinib has established efficacy in patients treated with one previous agent, its use in the frontline setting is currently the subject of ongoing research. Keywords: Advanced renal cell carcinoma; Axitinib; Oncology; Pharmacodynamics; Progression-free survival; Vascular endothelial growth factor receptor
INTRODUCTION K. Mittal () · L. S. Wood · B. I. Rini Taussig Cancer Institute, Cleveland Clinic, 9500 Euclid Avenue Desk R 35, Cleveland, Ohio 44195, USA e-mail: [email protected]
Enhanced content for Biologics in Therapy is available on the journal web site: www.biologicstherapy-open.com
The treatment of metastatic renal cell carcinoma (mRCC) has historically included immunotherapy, although targeted agents have revolutionized treatment strategies over the last several years. The management of mRCC has evolved rapidly since 2005, when sorafenib, a tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptor (VEGFR),
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was approved for advanced RCC following a phase 3 study in patients who had failed to respond to prior systemic therapy [1, 2]. Since then, newer VEGFR inhibitors, including sunitinib and pazopanib, have been approved in advanced renal cell carcinoma (RCC) in 2006 and 2009, respectively [3–5]. Additionally, bevacizumab, a monoclonal antibody to circulating vascular endothelial growth factor (VEGF), was approved in 2009 for mRCC patients in combination with interferon alpha [6, 7]. Newer, more biochemically potent VEGF-TKIs, such as axitinib, have expanded the armamentarium of available drugs with targeted action and established efficacy in mRCC. Angiogenesis and neovascularization are key to proliferation and dissemination of neoplasti
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