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Cancer Biology

Anti-Vascular Endothelial Growth Factor Therapies and Cardiovascular Toxicity: What Are the Important Clinical Markers to Target?

^aPhase 1 Program, Department of Investigational Cancer Therapeutics, and ^bDepartment of Cardiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA

Key Words. Vascular endothelial growth factor • Antiangiogenesis • Hypertension

Correspondence: Apostolia-Maria Tsimberidou, M.D., Ph.D., The University of Texas M. D. Anderson Cancer Center, Department of Investigational Cancer Therapeutics, Unit 455, 1515 Holcombe Boulevard, Houston, Texas 77030, USA. Telephone:713-792-4259; Fax:713-794-3249; e-mail: atsimber{at}mdanderson.org

Received October 15, 2009; accepted for publication January 18, 2010; first published online in THE ONCOLOGIST Express on February 5, 2010.

Disclosures

Christos Vaklavas: None; Daniel Lenihan: Consultant/advisory role: Oncomed, Immune Control; Research funding/contracted research: Biosite, Inc; Razelle Kurzrock: None; Apostolia Maria Tsimberidou: None.

Section editor Henk Verheul has disclosed no financial relationships relevant to the content of this article.

The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias.

Background. Therapies targeting vascular endothelial growth factor (VEGF) are associated with hypertension, cardiotoxicity, and thromboembolic events.

Methods. All prospective phase I–III clinical trials published up to December 2008 of approved anti-VEGF therapies (bevacizumab, sunitinib, sorafenib) and relevant literature were reviewed.

Results. The rates of Common Toxicity Criteria (version 3) grade 3–4 hypertension with bevacizumab, sunitinib, and sorafenib were 9.2%, 6.9%, and 7.2%, respectively. Grade 3–4 left ventricular systolic dysfunction was noted in 0.3%, 1.4%, and 0.05% of patients, respectively, whereas the rates of grade 3–4 thromboembolism were 9.6%, 1.2%, and 3.8%, respectively. The renin–angiotensin–aldosterone system (RAAS) may play a key role in vasoconstriction and capillary rarefaction, which are unleashed when VEGF signaling is targeted. Inhibiting RAAS may be the optimal approach for managing these toxicities.

Conclusions. In anticipation of cardiovascular complications with anti-VEGF therapies, early detection and personalized management may improve clinical outcomes and tolerance.