Cohen Martin H, Gootenberg Joe, Keegan Patricia, Pazdur Richard
Division of Biological Oncology Products, Office of Oncology Drug Products, Center for Drug Evaluation and Research, US Food and Drug Administration, HFD-150, 5600 Fishers Lane, Rockville, Maryland 20857, USA.
Oncologist. 2007 Mar;12(3):356-61. doi: 10.1634/theoncologist.12-3-356.
On June 20, 2006, the U.S. Food and Drug Administration (FDA) approved bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA), administered in combination with FOLFOX4 (5-fluorouracil, leucovorin, and oxaliplatin) for the second-line treatment of metastatic carcinoma of the colon or rectum. Efficacy and safety were demonstrated in one Eastern Cooperative Oncology Group (ECOG) open-label, multicenter, randomized, three-arm, active-controlled trial enrolling 829 adult patients. Patients had received a fluoropyrimidine- and irinotecan-based regimen as initial therapy for metastatic disease; or they had received prior adjuvant irinotecan-based chemotherapy and had recurred within 6 months of completing therapy. Treatments included bevacizumab, 10 mg/kg, as a 90-minute i.v. infusion on day 1, every 2 weeks, either alone or in combination with FOLFOX4, or FOLFOX4 alone. The bevacizumab monotherapy arm was closed to accrual after an interim efficacy analysis suggested a possibly shorter survival in that arm. Overall survival (OS), the primary study endpoint, was significantly longer for patients receiving bevacizumab in combination with FOLFOX4 than for those receiving FOLFOX4 alone. The objective response rate was significantly higher in the FOLFOX4 plus bevacizumab arm than in the FOLFOX4 alone arm. The duration of response was approximately 6 months for both treatment arms. Patients treated with the bevacizumab combination were also reported, based on investigator assessment, to have significantly longer progression-free survival. There were no new bevacizumab safety signals. The most serious, and sometimes fatal, bevacizumab toxicities are gastrointestinal perforation, wound-healing complications, hemorrhage, arterial thromboembolic events, hypertensive crisis, nephrotic syndrome, and congestive heart failure.
2006年6月20日，美国食品药品监督管理局（FDA）批准了贝伐单抗（阿瓦斯汀；基因泰克公司，加利福尼亚州南旧金山），其与FOLFOX4（5-氟尿嘧啶、亚叶酸钙和奥沙利铂）联合用于结肠或直肠癌转移癌的二线治疗。在一项东部肿瘤协作组（ECOG）开放标签、多中心、随机、三臂、活性对照试验中，纳入829例成年患者，证明了其疗效和安全性。患者接受过以氟嘧啶和伊立替康为基础的方案作为转移性疾病的初始治疗；或者他们之前接受过以伊立替康为基础的辅助化疗，且在完成治疗后6个月内复发。治疗方案包括：贝伐单抗，10mg/kg，在第1天静脉输注90分钟，每2周一次，可单独使用或与FOLFOX4联合使用，或仅使用FOLFOX4。在一项中期疗效分析表明该组可能生存期较短后，贝伐单抗单药治疗组停止入组。总生存期（OS）是主要研究终点，接受贝伐单抗联合FOLFOX4治疗的患者的总生存期显著长于仅接受FOLFOX4治疗的患者。FOLFOX4加贝伐单抗组的客观缓解率显著高于仅FOLFOX4组。两个治疗组的缓解持续时间均约为6个月。根据研究者评估，接受贝伐单抗联合治疗的患者无进展生存期也显著更长。未发现新的贝伐单抗安全信号。最严重且有时致命的贝伐单抗毒性包括胃肠道穿孔、伤口愈合并发症、出血、动脉血栓栓塞事件、高血压危象、肾病综合征和充血性心力衰竭。
