贝伐单抗联合奥沙利铂、氟尿嘧啶和亚叶酸钙（FOLFOX4）用于既往治疗过的转移性结直肠癌：东部肿瘤协作组E3200研究结果

Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200.

作者信息

Giantonio Bruce J, Catalano Paul J, Meropol Neal J, O'Dwyer Peter J, Mitchell Edith P, Alberts Steven R, Schwartz Michael A, Benson Al B

机构信息

University of Pennsylvania, Philadelphia, PA, USA.

出版信息

J Clin Oncol. 2007 Apr 20;25(12):1539-44. doi: 10.1200/JCO.2006.09.6305.

DOI:10.1200/JCO.2006.09.6305

PMID:17442997

Abstract

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.

摘要

目的

结直肠癌是美国癌症死亡的第二大主要原因。贝伐单抗联合化疗的抗血管生成疗法可提高先前未治疗的转移性结直肠癌患者的生存率。本研究旨在确定贝伐单抗（10mg/kg）对先前接受过治疗的转移性结直肠癌患者基于奥沙利铂的化疗生存期的影响。

患者与方法

829例先前接受过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（FOLFOX4）联合贝伐单抗；FOLFOX4不联合贝伐单抗；或单独使用贝伐单抗。主要终点是总生存期，同时还测定了无进展生存期、缓解率和毒性。

结果

FOLFOX4联合贝伐单抗治疗组的中位生存期为12.9个月，而单独使用FOLFOX4治疗组为10.8个月（相应的死亡风险比=0.75；P=0.0011），单独使用贝伐单抗治疗组为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，而单独使用FOLFOX4治疗组为4.7个月（相应的进展风险比=0.61；P<0.0001），单独使用贝伐单抗治疗组为2.7个月。相应的总缓解率分别为22.7%、8.6%和3.3%（FOLFOX4联合贝伐单抗与FOLFOX4比较，P<0.0001）。贝伐单抗与高血压、出血和呕吐有关。