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Anti-vascular endothelial growth factor therapies and cardiovascular toxicity: what are the important clinical markers to target?Vaklavas C; Lenihan D; Kurzrock R; Tsimberidou AMOncologist 2010[]; 15 (2): 130-41BACKGROUND: 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.|Angiogenesis Inhibitors/adverse effects[MESH]|Animals[MESH]|Antibodies, Monoclonal, Humanized[MESH]|Antibodies, Monoclonal/*adverse effects[MESH]|Antineoplastic Agents/adverse effects[MESH]|Benzenesulfonates/*adverse effects[MESH]|Bevacizumab[MESH]|Biomarkers/metabolism[MESH]|Cardiovascular Diseases/*chemically induced/metabolism[MESH]|Humans[MESH]|Indoles/*adverse effects[MESH]|Niacinamide/analogs & derivatives[MESH]|Phenylurea Compounds[MESH]|Pyridines/*adverse effects[MESH]|Pyrroles/*adverse effects[MESH]|Sorafenib[MESH]|Sunitinib[MESH]|Vascular Endothelial Growth Factor A/*antagonists & inhibitors/metabolism[MESH] |
