Clinical Use of Anti‐Vascular Endothelial Growth Factor Monoclonal Antibodies in Metastatic Colorectal Cancer

Vascular endothelial growth factor (VEGF) is the most potent proangiogenic factor and has been identified as an important target of cancer therapy Blocking endothelial cell VEGF activity inhibits tumor angiogenesis; normalizes tumor vasculature, facilitating improved chemotherapy delivery; and prevents the recruitment of progenitor cells from the bone marrow. Bevacizumab, the only United States Food and Drug Administration (FDA)‐approved anti‐VEGF agent, is a monoclonal antibody that inhibits the binding of VEGF to VEGF receptors. The addition of bevacizumab to standard first‐ and second‐line chemotherapy regimens for the treatment of metastatic colorectal cancer improves overall and progression‐free survival times and increases the time to disease progression. Studies are evaluating bevacizumab as adjuvant therapy. The optimal bevacizumab dosage is unknown, but 5 mg/kg every 2 weeks is currently recommended for initial therapy. A surrogate efficacy marker is needed to optimize bevacizumab use, both for dose and patient selection; the clinical applicability of several surrogate efficacy markers is being evaluated. Generally, bevacizumab is well tolerated; however, several serious adverse effects that may occur (e.g., hypertensive crisis) can usually be appropriately prevented or managed. Although current recommendations suggest the administration of the first bevacizumab dose over 90 minutes to prevent infusion‐related hypersensitivity reactions, recent study results show that 5 and 10 mg/kg can safely be administered over 10 and 20 minutes, respectively. Whether the addition of bevacizumab to metastatic colorectal cancer treatment regimens is a cost‐effective treatment option is unknown; health economic studies are needed. When used for FDA‐approved indications or for off‐label indications being evaluated in select clinical trials, Medicare reimburses for bevacizumab therapy.