Antiangiogenic agents in first-line and second-line therapy for advanced colorectal cancer

In the past 10 years, tremendous headway has been made in the fight against colorectal cancer. Advances have included the approval of new cytotoxic agents (oxaliplatin, irinotecan, and capecitabine), as well as biologic agents (cetuximab, bevacizumab, and panitumumab). Studies of bevacizumab, an antibody that targets vascular endothelial growth factor, provided the first proof of principle that addition of antiangiogenic therapy to chemotherapy provided a survival benefit for patients with previously untreated metastatic colorectal cancer. Since then, data have shown that bevacizumab treatment provides this same benefit in the second-line setting. Bevacizumab also appears to be effective when added to various chemotherapy regimens. The mechanisms of action of bevacizumab appear to involve both decreasing the number of abnormal tumor blood vessels that feed the tumor and preventing the growth of future blood vessels; and normalizing the abnormal tumor blood vessels to allow for better delivery of chemotherapy. Future research directions in the setting of metastatic colorectal cancer include continued evaluation of bevacizumab combined with different chemotherapeutic regimens, use of bevacizumab as maintenance therapy, continuation of bevacizumab through multiple lines of treatment, and bevacizumab combined with other biologic agents, such as epidermal growth factor receptor inhibitors.