Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Curr Opin Oncol. 2010 Jul;22(4):374-80. doi: 10.1097/CCO.0b013e328339524e.
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.
血管内皮生长因子（VEGF）系统是血管生成的关键调节剂，已知可促进结直肠癌（CRC）的肿瘤生长和侵袭。贝伐单抗是目前唯一在 CRC 中具有明确疗效的 VEGF 抑制剂，但在疾病的各个阶段最佳使用该药物仍在研究中。此外，还有许多其他针对 VEGF 和其他促血管生成系统的血管生成抑制剂正在临床开发中。
尽管贝伐单抗已被证明可改善转移性结直肠癌（mCRC）患者的无进展生存期和总生存期，但在辅助治疗中似乎并不能提供长期获益。VEGF 抑制与表皮生长因子抑制联合化疗并不能改善 mCRC 患者的生存率，并且在一线治疗中可能有潜在的危害。酪氨酸激酶抑制剂与其他疗法联合在 mCRC 的早期临床试验中显示出前景。
目前的证据表明，贝伐单抗抑制 VEGF 在 CRC 中的获益仅限于转移性疾病。mCRC 中不应使用贝伐单抗和表皮生长因子抑制剂（西妥昔单抗或帕尼单抗）的双重抗体治疗。正在进行的涉及酪氨酸激酶抑制剂的试验结果可能会扩大 CRC 患者的治疗选择。
