Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer
Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer
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DOI：
10.1056/nejmoa032691
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发表时间：
2004-06-03
影响因子：
158.5
通讯作者：
Kabbinavar, F
中科院分区：
文献类型：
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作者：
Hurwitz, H;Fehrenbacher, L;Kabbinavar, F
背景：贝伐珠单抗是一种抗血管内皮生长因子的单克隆抗体，在针对转移性结直肠癌的临床前和临床研究中已显示出良好的活性，特别是与化疗联合应用时。
方法：在813例先前未经治疗的转移性结直肠癌患者中，我们随机分配402例接受伊立替康、氟尿嘧啶推注和亚叶酸钙（IFL）联合贝伐珠单抗（每两周每千克体重5毫克）治疗，411例接受IFL联合安慰剂治疗。主要终点是总生存期。次要终点是无进展生存期、缓解率、缓解持续时间、安全性和生活质量。
结果：接受IFL联合贝伐珠单抗治疗组的中位生存期为20.3个月，而接受IFL联合安慰剂治疗组为15.6个月，相应的死亡风险比为0.66（P<0.001）。接受IFL联合贝伐珠单抗治疗组的无进展生存期为10.6个月，接受IFL联合安慰剂治疗组为6.2个月（风险比为0.54，P<0.001）。接受IFL联合贝伐珠单抗治疗组的缓解率为44.8%，接受IFL联合安慰剂治疗组为34.8%（P = 0.004）。两组的缓解持续时间中位数均为7.1个月。贝伐珠单抗治疗组最常见的不良反应是高血压（22.4%）、蛋白尿（11.0%）和鼻出血（10.0%）。接受IFL联合贝伐珠单抗治疗组的生活质量评分在大多数时间点与接受IFL联合安慰剂治疗组相似。
结论：在接受IFL治疗的转移性结直肠癌患者中，添加贝伐珠单抗可显著提高总生存期和无进展生存期，并提高缓解率，同时具有可接受的安全性和对生活质量无不良影响。
Background: Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, has shown promising preclinical and clinical activity against metastatic colorectal cancer, particularly in combination with chemotherapy.Methods: Of 813 patients with previously untreated metastatic colorectal cancer, we randomly assigned 402 to receive irinotecan, bolus fluorouracil, and leucovorin (IFL) plus bevacizumab (5 mg per kilogram of body weight every two weeks) and 411 to receive IFL plus placebo. The primary end point was overall survival. Secondary end points were progression-free survival, the response rate, the duration of the response, safety, and the quality of life.Results: The median duration of survival was 20.3 months in the group given IFL plus bevacizumab, as compared with 15.6 months in the group given IFL plus placebo, corresponding to a hazard ratio for death of 0.66 (P