Adverse effects of anticancer agents that target the VEGF pathway

• Published in: Nature reviews. Clinical oncology Vol. 6; no. 8; pp. 465 - 477
• Main Authors: Chen, Helen X, Cleck, Jessica N
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.08.2009; Nature Publishing Group
• Subjects: Angiogenesis Inhibitors - adverse effects; Angiogenesis Inhibitors - pharmacology; Angiogenesis Inhibitors - therapeutic use; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Antimitotic agents; Antineoplastic agents; Antineoplastic Agents - adverse effects; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Benzenesulfonates - adverse effects; Benzenesulfonates - pharmacology; Benzenesulfonates - therapeutic use; Bevacizumab; Brain Diseases - chemically induced; Cancer; Capillary Leak Syndrome - chemically induced; Cardiovascular Diseases - chemically induced; Cardiovascular Diseases - therapy; Care and treatment; Clinical Trials as Topic - statistics & numerical data; Colorectal cancer; Complications and side effects; Development and progression; Drug Delivery Systems; Drug Interactions; Forecasting; Gastrointestinal Diseases - chemically induced; Hemorrhage - chemically induced; Hemorrhage - therapy; Humans; Indoles - adverse effects; Indoles - pharmacology; Indoles - therapeutic use; Kidney Diseases - chemically induced; Kidney Diseases - therapy; Medicine; Medicine & Public Health; Neoplasm Proteins - antagonists & inhibitors; Neoplasm Proteins - physiology; Niacinamide - analogs & derivatives; Oncology; Phenylurea Compounds; Physiological aspects; Poisoning; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Pyridines - adverse effects; Pyridines - pharmacology; Pyridines - therapeutic use; Pyrroles - adverse effects; Pyrroles - pharmacology; Pyrroles - therapeutic use; Receptors, Vascular Endothelial Growth Factor - antagonists & inhibitors; Receptors, Vascular Endothelial Growth Factor - physiology; review-article; Risk Factors; Tumors; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - antagonists & inhibitors; Vascular Endothelial Growth Factor A - physiology; Wound Healing - drug effects
• ISSN: 1759-4774; 1759-4782
• DOI: 10.1038/nrclinonc.2009.94

Antiangiogenic agents that target the VEGF pathway have become an important part of standard therapy in multiple cancer indications. Although most adverse effects of VEGF inhibitors are modest and manageable, some are associated with serious and life-threatening consequences. This Review examines the toxicity profiles of anti-VEGF monoclonal antibodies and small-molecule inhibitors and considers the potential mechanisms of the adverse effects, risk factors, and the implications for patient management. Antiangiogenesis agents that target the VEGF/VEGF receptor pathway have become an important part of standard therapy in multiple cancer indications. With expanded clinical experience with this class of agents has come the increasing recognition of the diverse adverse effects related to disturbance of VEGF-dependent physiological functions and homeostasis in the cardiovascular and renal systems, as well as wound healing and tissue repair. Although most adverse effects of VEGF inhibitors are modest and manageable, some are associated with serious and life-threatening consequences, particularly in high-risk patients and in certain clinical settings. This Review examines the toxicity profiles of anti-VEGF antibodies and small-molecule inhibitors. The potential mechanisms of the adverse effects, risk factors, and the implications for selection of patients and management are discussed. Key Points Adverse effects associated with both VEGF- and VEGFR-targeting monoclonal antibodies and tyrosine kinase inhibitors are diverse, and include hypertension, arterial thromboembolic events, proteinuria, bowel perforation, reversible posterior leukoencephalopathy syndrome, wound complications and hemorrhage Risk of serious adverse events may be increased by a multitude of risk factors related to the tumor characteristics and locations, comorbidities, and prior or concurrent anticancer therapy Risk–benefit assessment is important for individual patients considering antiangiogenesis therapy In order to provide evidence-based guidance for risk identification, toxicity management and treatment adjustment for antiangiogenesis agents further research in this area is warranted