Prescrire Int. 2006 Jun;15(83):94-7.
(1) The prognosis for metastatic colorectal cancer is grim. The best treatment results are obtained by adding irinotecan to first-line fluorouracil + folinic acid therapy and then oxaliplatin to second-line fluorouracil + folinic acid therapy (or the reverse sequence), but median survival time still fails to exceed 2 years. (2) Bevacizumab is a monoclonal antibody directed against vascular endothelial growth factor (VEGF), a mediator involved in angiogenesis. Bevacizumab is marketed in Europe for first-line treatment of metastatic colorectal cancer, in combination with fluorouracil + folinic acid (with or without irinotecan). (3) The clinical evaluation includes 3 comparative trials. A double-blind trial involving 813 patients compared the American IFL protocol (irinotecan + fluorouracil + folinic acid) + placebo with the IFL protocol + bevacizumab. Median survival time was shorter with IFL + placebo (15.6 versus 20.3 months), but the results are difficult to extrapolate to the situation in Europe, where the FOLFIRI protocol is used (irinotecan + fluorouracil + folinic acid). This protocol is more effective than the IFL protocol. (4) Another double-blind trial, involving 204 patients, compared another American protocol, fluorouracil + folinic acid + placebo, with fluorouracil + folinic acid + bevacizumab. Median survival time did not differ significantly between the groups (12.9 and 16.6 months). (5) A combined analysis of 3 comparative trials showed an increase in median survival time of 3.3 months (17.9 versus 14.6 months) when bevacizumab was added to a fluorouracil + folinic acid combination. An indirect comparison suggests that this is no better than adding irinotecan. (6) In second-line treatment, preliminary data from a trial of bevacizumab + FOLFOX 4 (oxaliplatin + fluorouracil + folinic acid) fail to show a tangible benefit for bevacizumab. (7) Bevacizumab adjunction to current chemotherapy protocols increased the frequency of some potentially serious reactions, such as cardiovascular disorders (hypertension, arterial thrombosis); tumour haemorrhage; intestinal perforation; wound healing; and haematological disorders (severe leukopenia, etc.). (8) In practice, there is no evidence that bevacizumab is any better than current European chemotherapy protocols for first-line treatment of metastatic colorectal cancer.
（1）转移性结直肠癌的预后不容乐观。一线治疗采用氟尿嘧啶+亚叶酸钙联合伊立替康，二线治疗采用氟尿嘧啶+亚叶酸钙联合奥沙利铂（或顺序相反）可取得最佳治疗效果，但中位生存时间仍未超过2年。（2）贝伐单抗是一种针对血管内皮生长因子（VEGF）的单克隆抗体，VEGF是参与血管生成的介质。贝伐单抗在欧洲被批准用于转移性结直肠癌的一线治疗，与氟尿嘧啶+亚叶酸钙联合使用（可加或不加伊立替康）。（3）临床评估包括3项对比试验。一项涉及813例患者的双盲试验比较了美国IFL方案（伊立替康+氟尿嘧啶+亚叶酸钙）+安慰剂与IFL方案+贝伐单抗。IFL+安慰剂组的中位生存时间较短（15.6个月对20.3个月），但该结果难以推断至欧洲使用FOLFIRI方案（伊立替康+氟尿嘧啶+亚叶酸钙）的情况。该方案比IFL方案更有效。（4）另一项涉及204例患者的双盲试验比较了另一种美国方案，氟尿嘧啶+亚叶酸钙+安慰剂与氟尿嘧啶+亚叶酸钙+贝伐单抗。两组的中位生存时间无显著差异（12.9个月和16.6个月）。（5）3项对比试验的综合分析显示，在氟尿嘧啶+亚叶酸钙联合方案中加入贝伐单抗后，中位生存时间增加了3.3个月（17.9个月对14.6个月）。间接比较表明，这并不比加用伊立替康更好。（6）在二线治疗中，贝伐单抗+FOLFOX 4（奥沙利铂+氟尿嘧啶+亚叶酸钙）试验的初步数据未显示贝伐单抗有明显益处。（7）在当前化疗方案中加入贝伐单抗会增加一些潜在严重反应的发生率，如心血管疾病（高血压、动脉血栓形成）；肿瘤出血；肠穿孔；伤口愈合；以及血液系统疾病（严重白细胞减少等）。（8）实际上，没有证据表明贝伐单抗在转移性结直肠癌的一线治疗中比当前欧洲化疗方案更好。
