文章摘要

曲妥珠单抗治疗乳腺癌患者心脏毒性的Meta分析

作者: 1李信娟, 1黄浪, 1周建国, 1申莎莎, 2,3马虎
1 遵义医学院附属肿瘤医院胸部肿瘤科,贵州 遵义 563099
2 遵义医学院附属肿瘤医院胸部肿瘤科,贵州 遵义 563099
3 贵州省生物治疗人才基地及遵义医学院 转化医学研究中心,贵州 遵义 563099
通讯: 马虎 Email: mahuab@163.com
DOI: 10.3978/j.issn.2095-6959.2017.08.023

摘要

目的:探讨HER2阳性乳腺癌患者在接受曲妥珠单抗治疗后心脏毒性的发生情况。方法:搜索PubMed,EMBASE,Web of Science和Cochrane图书馆查找相关文献,检索日期从建库至2016年12月,根据纳入及排除标准收集III期RCT,按Cochrane Handbook 5.1.0系统评价方法,由2名评价者独立评价纳入研究质量,并提取数据及交叉核对。结果采用R软件进行Meta分析,比较曲妥珠单抗与传统治疗导致乳腺癌患者心脏毒性的发生情况及分级。结果以相对危险度(risk ratio,RR)、95%CI表示。结果:纳入6篇文章,共18 622例患者,其中使用曲妥珠单抗者11 766例,对照组6 856例。Meta分析结果显示:实验组相较于对照组,II级以上心脏毒性事件的发生明显增加(RR=3.56,95%CI 1.52~8.33,P<0.001),III,IV级心脏毒性的发生率更高(RR=2.89,95%CI 1.77~4.71,P<0.001),对于心源性死亡的发生,差异无统计学意义(RR=0.50,95%CI 0.12~2.05,P=0.334)。亚组分析结果显示:欧洲II级以上心脏毒性发生率显著高于美国。而在含与不含紫杉醇、蒽环类的亚组分析中,前者并未增加患者II,III级以上心脏毒性发生率。结论:在HER2阳性乳腺癌患者中,使用曲妥珠单抗治疗可增加II,III级以上心脏毒性的发生率,但并不会增加心源性死亡的发生。
关键词: 乳腺癌 HER2阳性 曲妥珠单抗 心脏毒性 meta分析

Cardiotoxicity of trastuzumab in breast cancer patients: a meta-analysis

Authors: 1LI Xinjuan, 1HUANG Lang, 1ZHOU Jianguo, 1SHEN Shasha, 2,3MA Hu
1 Department of Thoracic Oncology, Tumor Hospital of Zunyi Medical University, Zunyi Guizhou 563099
2 Department of Thoracic Oncology, Tumor Hospital of Zunyi Medical University, Zunyi Guizhou 563099
3 Biological Treatment Talent Base of Guizhou Province and Translation Medicine Research Center of Zunyi Medical University, Zunyi Guizhou 563099, China

CorrespondingAuthor: MA Hu Email: mahuab@163.com

DOI: 10.3978/j.issn.2095-6959.2017.08.023

Abstract

Objective: To investigate the incidence and classification of cardiac toxicity in patients with HER2 positive breast cancer who treated with trastuzumab. Methods: The relevant literature were searched in PubMed, EMBASE, Web of Science and Cochrane library until December, 2016. Phase III RCTs were included according to inclusion criteria for screening and assessment of the literature ultimately. As the system evaluation method of Cochrane Handbook 5.1.0, the literature was screened, data were extracted and checked by 2 reviewers respectively. Meta-analysis was then performed using R software to compare the treatment of trastuzumab and traditional treatment on cardiotoxicity in patients with breast cancer. Results expressed as the relative risk (RR) and 95% confidence interval (CI). Results: A total of 6 RCTs involving 18 622 patients were finally included, of which 11 766 cases in trastuzumab group, and 6 856 cases in the control group. Compared with the control group, Meta-analysis showed the occurrence of cardiac toxicity events which above grade II increased significantly in experience group (RR=3.56, 95%CI 1.52–8.33, P<0.001). While the incidence of grade III–IV was higher(RR=2.89, 95%CI 1.77–4.71, P<0.001). However, differences in the aspect of cardiac death had no significance. Subgroup analysis shows that the cardiotoxicity of grade II by trastuzumab in Europe was higher than that of the United states. But there was no difference between the group that contains paclitaxel and/or anthracyclines and the group of without paclitaxel and anthracycline. Conclusion: This pooled analysis suggests that trastuzumab for patients with HER2 overexpress breast cancer is associate with increased risk of adverse cardiac events upon grade II, III. Nevertheless ,there is no significant difference in the occurrence of cardiac death.
Keywords: breast cancer HER2 positive trastuzumab cardiotoxicity meta-analysis

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