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贝伐珠单抗改善晚期宫颈癌患者的生存情况
Improved Survival with Bevacizumab in Advanced Cervical Cancer


Krishnansu S. Tewari ... 肿瘤 妇产科和儿科 • 2014.02.20
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摘要


背景

血管内皮生长因子(VEGF)可促进血管生成,是宫颈癌发展的调节因子。贝伐珠单抗是人源化抗VEGF单克隆抗体,在既往接受过治疗及复发的宫颈癌患者中具有单药抗肿瘤活性。大多数之前接受过顺铂与放疗的宫颈癌患者肿瘤复发时,顺铂的有效性明显减低。本文评估了贝伐珠单抗与非铂类药物联合化疗方案对复发性、持续性或转移性宫颈癌的有效性。


方法

采用2×2析因设计,452名患者被随机分配为两组,一组为单纯化疗组,另一组在化疗基础上加用贝伐珠单抗(15 mg/kg)。化疗方案包括在第一天至第三天服用顺铂50 mg/m2+紫杉醇135或175 mg/m2,或在第一天服用拓扑替康0.75 mg/m2+第一天紫杉醇175 mg/m2。上述方案每21天重复1次,直至疾病进展,出现无法耐受的毒性反应,或疾病获得完全缓解。主要终点是总生存期,死亡风险比减少30%被认为有临床意义。


结果

各组患者在年龄、病理类型、体力状况评分、之前是否应用过铂类药物作为放射性增敏剂和疾病状态等方面较为平衡。拓扑替康-紫杉醇方案并不优于顺铂-紫杉醇方案(死亡风险比1.20)。两种化疗方案的联合数据显示,与单纯化疗相比,贝伐珠单抗联合化疗可提高患者的总生存期(17.0个月对13.3个月;风险比,0.71;98% CI,0.54~0.95;单侧检验P=0.004),并提高化疗缓解率(48%对36%,P=0.008)。与单纯化疗相比,贝伐珠单抗联合化疗组副反应增加,包括2级及以上的高血压(25%对2%),3级或以上的血栓栓塞事件(8%对1%)和3级或以上的胃肠道穿孔(3%对0%)。


结论

联合化疗加上贝伐珠单抗可使复发、持续或转移性宫颈癌患者的中位总生存期提高3.7个月(本研究由美国国家癌症研究[National Cancer Institute]所资助;GOG 240在ClinicalTrials.gov注册号为NCT00803062)。





作者信息

Krishnansu S. Tewari, M.D., Michael W. Sill, Ph.D., Harry J. Long, III, M.D., Richard T. Penson, M.D., Helen Huang, M.S., Lois M. Ramondetta, M.D., Lisa M. Landrum, M.D., Ana Oaknin, M.D., Thomas J. Reid, M.D., Mario M. Leitao, M.D., Helen E. Michael, M.D., and Bradley J. Monk, M.D.
From the University of California, Irvine, Medical Center, Orange (K.S.T.); Roswell Park Cancer Institute, State University of New York at Buffalo, Buffalo (M.W.S., H.H.); Mayo Clinic, Rochester, MN (H.J.L.); Massachusetts General Hospital, Boston (R.T.P.); M.D. Anderson Cancer Center, Houston (L.M.R.); University of Oklahoma, Oklahoma City (L.M.L.); Vall d'Hebron University Hospital, Barcelona (A.O.); University of Cincinnati College of Medicine–Women's Cancer Center at Kettering, Kettering, OH (T.J.R.); Memorial Sloan-Kettering Cancer Center, New York (M.M.L.); Indiana University School of Medicine, Indianapolis (H.E.M.); and the University of Arizona Cancer Center and Creighton University at St. Joseph's Hospital and Medical Center, Phoenix (B.J.M.). Address reprint requests to Dr. Tewari at the Division of Gynecologic Oncology, University of California, Irvine, Medical Center, 101 City Dr. S., Bldg. 56, Orange, CA 92868, or at ktewari@uci.edu.

 

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