Mulcahy Mary F, Benson Al B
Division of Hematology/Oncology, Department of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Feinberg School of Medicine, 676 North Saint Clair, Suite 850, Chicago, IL 60611, USA.
Expert Opin Biol Ther. 2005 Jul;5(7):997-1005. doi: 10.1517/14712598.5.7.997.
Bevacizumab is a humanised monoclonal antibody that inhibits vascular endothelial growth factor (VEGF), the key mediator of tumour angiogenesis, and has been shown to improve survival when given with chemotherapy to patients with metastatic colorectal cancer. In a pivotal Phase III clinical trial, 813 subjects were treated with irinotecan, 5-fluorouracil (5-FU) and leucovorin and randomised to receive placebo or bevacizumab. Median survival for the group receiving bevacizumab was increased by 30%, from 15.6 to 20.3 months (p < or = 001). Other Phase II and III studies in colorectal cancer have demonstrated a benefit when bevacizumab is added to regimens of 5-FU and leucovorin, and 5-FU, leucovorin and oxaliplatin. The toxicity associated with bevacizumab is generally mild, consisting of manageable hypertension, clinically insignificant proteinuria and mild mucosal bleeding. Infrequent severe toxicities have been reported, consisting of arterial thrombosis and gastrointestinal perforations (1.5%). Bevacizumab represents the first angiogenesis modulator that has a proven benefit in cancer therapy.
贝伐单抗是一种人源化单克隆抗体，可抑制血管内皮生长因子（VEGF），而VEGF是肿瘤血管生成的关键介质。研究表明，对于转移性结直肠癌患者，贝伐单抗与化疗联合使用可提高生存率。在一项关键的III期临床试验中，813名受试者接受了伊立替康、5-氟尿嘧啶（5-FU）和亚叶酸治疗，并随机分为两组，分别接受安慰剂或贝伐单抗治疗。接受贝伐单抗治疗组的中位生存期延长了30%，从15.6个月增至20.3个月（p≤0.01）。其他针对结直肠癌的II期和III期研究表明，在5-FU和亚叶酸、5-FU、亚叶酸和奥沙利铂方案中加入贝伐单抗均有获益。与贝伐单抗相关的毒性通常较轻，包括可控的高血压、临床意义不大的蛋白尿和轻度黏膜出血。已报告的罕见严重毒性包括动脉血栓形成和胃肠道穿孔（1.5%）。贝伐单抗是首个在癌症治疗中被证实有获益的血管生成调节剂。
