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浙江大学学报（医学版）
浙江大学学报（医学版）  2016, Vol. 45 Issue (4): 379-386    DOI: 10.3785/j.issn.1008-9292.2016.07.08
癌分子医学专题     
贝伐珠单克隆抗体联合化疗用于Her2阴性乳腺癌患者新辅助治疗的meta分析
韩瑞, 王冠英, 张玉姣, 赵新汉
西安交通大学医学院第一附属医院肿瘤内科, 陕西 西安 710061
Efficacy of neoadjuvant chemotherapy combined with bevacizumab versus neoadjuvant chemotherapy alone for Her2-negative breast cancer: a meta-analysis of randomized controlled clinical trials
HAN Rui, WANG Guanying, ZHANG Yujiao, ZHAO Xinhan
Department of Oncology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
全文: PDF(1018 KB)  
摘要: 

目的：评价贝伐珠单克隆抗体（贝伐珠单抗）联合化疗在Her2阴性乳腺癌患者新辅助治疗中的有效性和安全性。方法：检索PubMed、the Cochrane Library、Web of Science、中国期刊全文数据库、万方医药期刊全文数据库和近5年重要国际肿瘤学会议摘要，严格按照纳入与排除标准收集Her2阴性乳腺癌患者使用新辅助化疗联合贝伐珠单抗（联合组）对比单用新辅助化疗（化疗组）的有效性和安全性的前瞻性随机对照研究。按Cochrane系统评价方法进行质量评价，资料提取后运用RevMan 5.3软件进行meta分析。结果：最终纳入六项随机对照临床试验，共4440例患者符合条件。Meta分析结果显示，联合组较化疗组病理完全缓解率有所提高（24.7%与20.1%，RR=1.23，95%CI：1.10~1.37，P<0.01）；联合组无论激素受体是否阳性均可提高病理完全缓解率（激素受体阳性亚组：13.1%与10.2%，RR=1.28，95%CI：1.04~1.58，P<0.05；激素受体阴性亚组：46.3%与37.1%，RR=1.25，95%CI：1.12~1.39，P<0.01）；联合组高血压（3.2%与0.6%，RR=5.292，95%CI：2.933~9.549，P<0.01）、黏膜炎（10.5%与2.0%，RR=5.340，95%CI：3.743~7.617，P<0.01）的发生率更高，其他不良反应如中性粒细胞减少性发热、感染、手术并发症、中性粒细胞减少、手足综合征联合组的发生率均高于化疗组（均P<0.05），而周围神经病变发生率两组间差异并无统计学意义（P>0.05）。结论：在Her2阴性乳腺癌患者的新辅助治疗中，不论患者激素受体阳性与否，采用新辅助化疗联合贝伐珠单抗靶向治疗效果较好，但一些不良反应发生率也相应增加，需要更多的临床研究来筛选出优势人群。
关键词 ： Meta分析,  乳腺肿瘤/药物疗法,  抗体,单克隆/治疗应用,  受体,表皮生长因子/分析,  化学疗法,辅助    
Abstract：

Objective: To evaluate the efficacy and safety of neoadjuvant chemotherapy combined with bevacizumab versus neoadjuvant chemotherapy alone for Her2-negative breast cancer.Methods: We searched PubMed, the Cochrane Library, Web of Science, CNKI, Wanfang Database and the abstracts of major international conferences in recent 5 years to identify prospective randomized controlled clinical trials that met the inclusion and exclusion criteria. Study selection and analyses were undertaken according to the Cochrane Handbook. Meta-analysis was performed using RevMan 5.3 software.Results: Six trials were identified with 4440 eligible patients. The results of this meta-analysis showed that the rate of pathological complete response (pCR) was higher in Her-2 negative breast cancer patients receiving bevacizumab combined with neoadjuvant chemotherapy than that in patients with neoadjuvant chemotherapy alone (24.7% vs 20.1%, RR=1.23, 95%CI:1.10-1.37, P<0.01). In addition, the pCR rate rose up when bevacizumab was added to neoadjuvant chemotherapy both in hormone receptor-positive patients (13.1% vs 10.2%,RR=1.28, 95%CI:1.04-1.58,P<0.05) and in hormone receptor-negative patients (46.3% vs 37.1%, RR=1.25, 95%CI:1.12-1.39, P<0.01). Statistical differences were observed in the rate of relevant adverse events such as hypertention (3.2% vs 0.6%, RR=5.292, 95%CI:2.933-9.549, P<0.01) and mucositis (10.5% vs 2.0%, RR=5.340, 95%CI:3.743-7.617, P<0.01) between the combination group and the chemotherapy alone group. Differences in other toxicities such as febrile neutropenia, infection, surgical complications, neutropenia and hand-foot syndrome were also found to be statistically significant between the combination group and the chemotherapy alone group (all P<0.05), while such difference was not found in the occurrence of peripheral neuropathy (P>0.05). Conclusion: The addition of bevacizumab to neoadjuvant chemotherapy in Her2-negative breast cancer can significantly improve pathological complete response, but may bring more grade 3 and 4 toxicities.More neoadjuvant trials need to be done to define subgroups of Her2-negative breast cancer that would have clinically significant long-term benefit from bevacizumab treatment.
Key words： Meta-analysis    Breast neoplasms/drug therapy    Antibodies, monoclonal/therapeutic use    Receptor, epidermal growth factor/analysis    Chemotherapy, adjuvant
收稿日期: 2016-06-03
CLC:  R686  
通讯作者: 赵新汉(1964-),男,博士,教授,博士生导师,主要从事肿瘤综合治疗和靶向基因治疗研究;E-mail:zhaoxinhanprof@163.com;http://orcid.org/0000-0002-8525-4178     E-mail: zhaoxinhanprof@163.com
作者简介: 韩瑞(1991-),女,博士研究生,主要从事肿瘤综合治疗和靶向基因治疗研究;E-mail:13119190368@163.com;http://orcid.org/0000-0003-2612-3570
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引用本文:

韩瑞 等. 贝伐珠单克隆抗体联合化疗用于Her2阴性乳腺癌患者新辅助治疗的meta分析[J]. 浙江大学学报（医学版）, 2016, 45(4): 379-386.
HAN Rui, WANG Guanying, ZHANG Yujiao, ZHAO Xinhan. Efficacy of neoadjuvant chemotherapy combined with bevacizumab versus neoadjuvant chemotherapy alone for Her2-negative breast cancer: a meta-analysis of randomized controlled clinical trials. Journal of ZheJiang University(Medical Science), 2016, 45(4): 379-386.

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http://www.zjujournals.com/xueshu/med/CN/10.3785/j.issn.1008-9292.2016.07.08      或      http://www.zjujournals.com/xueshu/med/CN/Y2016/V45/I4/379

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