Anti-vascular endothelial growth factor therapies and cardiovascular toxicity: what are the important clinical markers to target?

Oncologist. 2010;15(2):130-41. doi: 10.1634/theoncologist.2009-0252. Epub 2010 Feb 5.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiogenesis Inhibitors / adverse effects
  • Animals
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / adverse effects
  • Benzenesulfonates / adverse effects*
  • Bevacizumab
  • Biomarkers / metabolism
  • Cardiovascular Diseases / chemically induced*
  • Cardiovascular Diseases / metabolism
  • Humans
  • Indoles / adverse effects*
  • Niacinamide / analogs & derivatives
  • Phenylurea Compounds
  • Pyridines / adverse effects*
  • Pyrroles / adverse effects*
  • Sorafenib
  • Sunitinib
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Benzenesulfonates
  • Biomarkers
  • Indoles
  • Phenylurea Compounds
  • Pyridines
  • Pyrroles
  • Vascular Endothelial Growth Factor A
  • Niacinamide
  • Bevacizumab
  • Sorafenib
  • Sunitinib