Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: Results from the Eastern Cooperative Oncology Group Study E3200
Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: Results from the Eastern Cooperative Oncology Group Study E3200
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DOI：
10.1200/jco.2006.09.6305
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发表时间：
2007-04-20
影响因子：
45.3
通讯作者：
Benson, Al B., III
中科院分区：
文献类型：
--
作者：
Giantonio, Bruce J.;Catalano, Paul J.;Benson, Al B., III
在美国，结直肠癌是导致癌症死亡的第二大原因。贝伐单抗联合化疗的抗血管生成治疗提高了先前未经治疗的转移性结直肠癌的生存率。本研究旨在确定贝伐单抗（10mg /kg）对先前治疗过的转移性结直肠癌患者奥沙利铂化疗的生存时间的影响。患者和方法829例先前接受氟嘧啶和伊立替康治疗的转移性结直肠癌患者被随机分配到三个治疗组之一：奥沙利铂、氟尿嘧啶和亚叶酸钙（FOLFOX4）联合贝伐单抗；FOLFOX4不含贝伐单抗；或者单独使用贝伐单抗。主要终点是总生存期，并附加无进展生存期、反应和毒性的测定。结果FOLFOX4联合贝伐单抗治疗组的中位生存期为12.9个月，而FOLFOX4单独治疗组的中位生存期为10.8个月（相应的死亡风险比= 0.75;P = 0.0011），贝伐单抗单独治疗组的中位生存期为10.2个月。FOLFOX4联合贝伐单抗治疗组的中位无进展生存期为7.3个月，而FOLFOX4单独治疗组的中位无进展生存期为4.7个月（相应的进展风险比= 0.61;P < 0.0001），贝伐单抗单独治疗组的中位无进展生存期为2.7个月。相应的总缓解率分别为22.7%、8.6%和3.3% （FOLFOX4与贝伐单抗与FOLFOX4的比较P < 0.0001）。贝伐单抗与高血压、出血和呕吐相关。结论贝伐单抗联合奥沙利铂、氟尿嘧啶和亚叶酸钙可改善转移性结直肠癌患者的生存期。
Purpose Colorectal cancer is the second leading cause of cancer mortality in the United States. Antiangiogenic therapy with bevacizumab combined with chemotherapy improves survival in previously untreated metastatic colorectal cancer. This study was conducted to determine the effect of bevacizumab (at 10 mg/kg) on survival duration for oxaliplatin-based chemotherapy in patients with previously treated metastatic colorectal cancer.Patients and Methods Eight hundred twenty-nine metastatic colorectal cancer patients previously treated with a fluoropyrimidine and irinotecan were randomly assigned to one of three treatment groups: oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) with bevacizumab; FOLFOX4 without bevacizumab; or bevacizumab alone. The primary end point was overall survival, with additional determinations of progression-free survival, response, and toxicity.Results The median duration of survival for the group treated with FOLFOX4 and bevacizumab was 12.9 months compared with 10.8 months for the group treated with FOLFOX4 alone (corresponding hazard ratio for death = 0.75; P = .0011), and 10.2 months for those treated with bevacizumab alone. The median progression-free survival for the group treated with FOLFOX4 in combination with bevacizumab was 7.3 months, compared with 4.7 months for the group treated with FOLFOX4 alone (corresponding hazard ratio for progression = 0.61; P < .0001), and 2.7 months for those treated with bevacizumab alone. The corresponding overall response rates were 22.7%, 8.6%, and 3.3%, respectively (P < .0001 for FOLFOX4 with bevacizumab v FOLFOX4 comparison). Bevacizumab was associated with hypertension, bleeding, and vomiting.Conclusion The addition of bevacizumab to oxaliplatin, fluorouracil, and leucovorin improves survival duration for patients with previously treated metastatic colorectal cancer.