Antiangiogenesis agents in colorectal cancer

Abstract

The vascular endothelial growth factor (VEGF) system is a critical regulator of angiogenesis and known to promote tumor growth and invasion in colorectal cancer (CRC). Bevacizumab is currently the only VEGF inhibitor with clear proof of efficacy in CRC, but optimal use of this agent at various stages of the disease is still under investigation. Additionally, there are numerous other angiogenesis agents targeting VEGF and other proangiogenic systems in clinical development. Although bevacizumab has been shown to improve outcomes in terms of progression-free and overall survival in the setting of metastatic CRC (mCRC), it does not appear to provide long-term benefit in the adjuvant setting. The combination of VEGF inhibition with epidermal growth factor inhibition with chemotherapy does not improve survival for patients with mCRC, and may potentially be harmful in the first-line setting. Tyrosine kinase inhibitors in combination with other therapies show promise in early clinical trials in mCRC. Current evidence suggests that the benefit of VEGF inhibition with bevacizumab in CRC is limited to the metastatic setting. Dual antibody therapy with bevacizumab and an epidermal growth factor inhibitor (cetuximab or panitumumab) should not be used in mCRC. Results of ongoing trials involving tyrosine kinase inhibitors may result in an expansion of treatment options for patients with CRC.