Adverse effects of anticancer agents that target the VEGF pathway.
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.
Chen
Helen X
HX
Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD 20851, USA. helen.chen@nih.gov
Cleck
Jessica N
JN
D020533:Angiogenesis Inhibitors / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D001557:Benzenesulfonates / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000068258:Bevacizumab; D001927:Brain Diseases / Q000139:chemically induced; D019559:Capillary Leak Syndrome / Q000139:chemically induced; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000628:therapy; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D016503:Drug Delivery Systems; D004347:Drug Interactions; D005544:Forecasting; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006470:Hemorrhage / Q000139:chemically induced* / Q000628:therapy; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D007674:Kidney Diseases / Q000139:chemically induced* / Q000628:therapy; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D011725:Pyridines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D011758:Pyrroles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors* / Q000502:physiology; D012307:Risk Factors; D000077157:Sorafenib; D000077210:Sunitinib; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000502:physiology; D014945:Wound Healing / Q000187:drug effects
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D007211:Indoles; D009363:Neoplasm Proteins; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011758:Pyrroles; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D009536:Niacinamide; D000068258:Bevacizumab; D000077157:Sorafenib; D040262:Receptors, Vascular Endothelial Growth Factor; D000077210:Sunitinib