Ciombor Kristen K, Goldberg Richard M
Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, OH.
Curr Colorectal Cancer Rep. 2015 Dec;11(6):378-387. doi: 10.1007/s11888-015-0292-3.
Angiogenesis is a complex biologic process critical to growth and proliferation of colorectal cancer. The safety and efficacy of various anti-angiogenic agents have been investigated in many treatment settings. Bevacizumab, an anti-vascular endothelial growth factor agent, has efficacy in both the first-line setting and beyond progression in metastatic colorectal cancer. The decoy vascular endothelial growth factor receptor aflibercept has been approved in combination with 5-fluorouracil, leucovorin and irinotecan-based chemotherapy in metastatic colorectal cancer patients whose disease has progressed on a prior oxaliplatin-based chemotherapy regimen. The multikinase inhibitor regorafenib is modestly effective in the refractory colorectal cancer setting but confers significant toxicity. Ramucirumab, an anti-vascular endothelial growth factor receptor 2 molecule, has efficacy in combination with 5-fluorouracil, leucovorin and irinotecan after disease progression on a first-line bevacizumab-, oxaliplatin- and fluoropyrimidine-containing regimen. Questions regarding optimal treatment setting, predictive biomarkers of response, and cost effectiveness of these anti-angiogenic agents and others are as yet unanswered.
血管生成是一种对结直肠癌的生长和增殖至关重要的复杂生物学过程。在许多治疗环境中，已经对各种抗血管生成药物的安全性和有效性进行了研究。贝伐单抗是一种抗血管内皮生长因子药物，在转移性结直肠癌的一线治疗及疾病进展后均有疗效。诱骗性血管内皮生长因子受体阿柏西普已被批准与基于5-氟尿嘧啶、亚叶酸钙和伊立替康的化疗联合用于疾病在先前基于奥沙利铂的化疗方案中进展的转移性结直肠癌患者。多激酶抑制剂瑞戈非尼在难治性结直肠癌环境中疗效一般，但毒性显著。雷莫西尤单抗是一种抗血管内皮生长因子受体2分子，在一线含贝伐单抗、奥沙利铂和氟嘧啶的方案疾病进展后，与5-氟尿嘧啶、亚叶酸钙和伊立替康联合使用有疗效。关于这些抗血管生成药物及其他药物的最佳治疗环境、反应预测生物标志物和成本效益等问题尚未得到解答。
