曲妥珠单抗相关不良反应的监测及防治研究进展

doi:10.3969/j.issn.1674-490X.2020.03.005

摘要/Abstract

摘要： 曲妥珠单抗是人表皮生长因子受体-2(human epidermal growth factor receptor-2,HER-2)的特异性拮抗剂,是治疗乳腺癌的第一个分子靶向药物,自1998年上市以来,已有20余年的临床应用史。但随着应用时间的延长,其引发的不良反应报道也越来越多。通过查阅文献,就曲妥珠单抗相关不良反应的类型、监测及防治手段进行了综述,为临床合理用药提供参考。

关键词: 曲妥珠单抗, 不良反应, 心脏毒性, 监测, 防治

Abstract: Trastuzumab is a specific antagonist of human epidermal growth factor receptor-2(HER-2). It is the first molecular-targeted drug for the treatment of breast cancer. Since its market debut in 1998, trastuzumab has been in clinical application for more than 20 years. However, with the extension of clinical application, more and more adverse reactions are reported. By consulting the literature, the types, monitoring and prevention of trastuzumab related adverse reactions were reviewed in this paper so as to provide reference for clinical rational drug use.

Key words: trastuzumab, adverse reactions, cardiotoxicity, monitoring, prevention

中图分类号:

毕亮亮, 韩若凌, 焦子义. 曲妥珠单抗相关不良反应的监测及防治研究进展[J]. 医学研究与教育, 2020, 37(3): 32-38.

参考文献

[1] 沈媛, 陆琳, 王晓玉. 赫赛汀诱导子宫内膜癌Ishikawa细胞凋亡并增强其对化疗的敏感性[J]. 中国病理生理杂志, 2015, 31(9): 1568-1571. DOI: 10.3969/j.issn.1000-4718.2015.09.006.
[2] AITELHAJ M, LKHOUYAALI S, RAIS G, et al. Cardiac safety of the adjuvant trastuzumab in a moroccan population: observational monocentric study of about 100 patients[J]. BMC Res Notes, 2013, 6: 339. DOI: 10.1186/1756-0500-6-339.
[3] FAROLFI A, MELEGARI E, AQUILINA M, et al. Trastuzumab-induced cardiotoxicity in early breast cancer patients: a retrospective study of possible risk and protective factors[J]. Heart, 2013, 99(9): 634-639. DOI: 10.1136/heartjnl-2012-303151.
[4] EWER M S, VOOLETICH M T, DURAND J B, et al. Reversibility of trastuzumab-related cardiotoxicity: new insights based on clinical course and response to medical treatment[J]. J Clin Oncol, 2005, 23(31): 7820-7826. DOI: 10.1200/jco.2005.13.300.
[5] TSAI H T, ISAACS C, FU A Z, et al. Risk of cardiovascular adverse events from trastuzumab(Herceptin^®)in elderly persons with breast cancer: a population-based study[J]. Breast Cancer Res Treat, 2014, 144(1): 163-170. DOI: 10.1007/s10549-014-2836-7.
[6] 曾慧, 唐雪苗. 曲妥珠单抗在乳腺癌患者治疗中的心脏毒性[J]. 实用医学杂志, 2017, 33(12): 2056-2058. DOI: 10.3969/j.issn.1006-5725.2017.12.044.
[7] 薛剑, 金欣, 于农, 等. 心电图对曲妥珠单抗介导心脏毒性的预测价值[J]. 中国循证心血管医学杂志, 2014, 6(6): 693-695. DOI: 10.3969/j.1674-4055.2014.06.11.
[8] TELLI M L, HUNT S A, CARLSON R W, et al. Trastuzumab-related cardiotoxicity: calling into question the concept of reversibility[J]. J Clin Oncol, 2007, 25(23): 3525-3533. DOI: 10.1200/jco.2007.11.0106.
[9] KASNER M, WESTERMANN D, STEENDIJK P, et al. Utility of Doppler echocardiography and tissue Doppler imaging in the estimation of diastolic function in heart failure with normal ejection fraction[J]. Circulation, 2007, 116(6): 637-647. DOI: 10.1161/circulationaha.106.661983.
[10] 杨菲, 陈勇, 张西志, 等. 超声心动图评价乳腺癌患者曲妥珠单抗靶向药物治疗后早期心脏毒性的价值[J]. 实用临床医药杂志, 2016, 20(11): 99-101. DOI: 10.7619/jcmp.201611028.
[11] CAO L, CAI G, CHANG C, et al. Diastolic dysfunction occurs early in HER2-positive breast cancer patients treated concurrently with radiation therapy and trastuzumab[J]. Oncol, 2015, 20(6): 605-614. DOI: 10.1634/theoncologist.2014-0299.
[12] COLLIER P, PHELAN D, KLEIN A. A test in context: myocardial strain measured by speckle-tracking echocardiography[J]. J Am Coll Cardiol, 2017, 69(8): 1043-1056. DOI: 10.1016/j.jacc.2016.12.012.
[13] EMREN S V, TULUCE S Y, LEVENT F, et al. Evaluation of Trastuzumab-induced early cardiac dysfunction using two-dimensional strain echocardiography[J]. Med Ultrason, 2015, 17(4): 496-502. DOI: 10.11152/mu.2013.2066.174.tzb.
[14] 郑军, 李晶, 李树深, 等. 二维斑点追踪成像技术评价乳腺癌患者曲妥珠单抗药物靶向治疗后左室早期心肌功能的损害[J]. 宁夏医学杂志, 2017, 39(12): 1151-1153. DOI: 10.13621/j.1001-5949.2017.12.1151.
[15] ARCINIEGAS CALLE M C, SANDHU N P, XIA H M, et al. Two-dimensional speckle tracking echocardiography predicts early subclinical cardiotoxicity associated with anthracycline-trastuzumab chemotherapy in patients with breast cancer[J]. BMC Cancer, 2018, 18: 1037. DOI: 10.1186/s12885-018-4935-z.
[16] MOUSTAFA S, MURPHY K, NELLURI B K, et al. Temporal trends of cardiac Chambers function with trastuzumab in human epidermal growth factor receptor II-positive breast cancer patients[J]. Echocardiography, 2016, 33(3): 406-415. DOI: 10.1111/echo.13087.
[17] MIYOSHI T, TANAKA H, KANEKO A, et al. Left ventricular endocardial dysfunction in patients with preserved ejection fraction after receiving anthracycline[J]. Echocardiography, 2014, 31(7): 848-857. DOI: 10.1111/echo.12473.
[18] WEN H, LIANG Z, ZHAO Y, et al. Feasibility of detecting early left ventricular systolic dysfunction using global area strain: a novel index derived from three-dimensional speckle-tracking echocardiography[J]. Eur J Echocardiogr, 2011, 12(12): 910-916. DOI: 10.1093/ejechocard/jer162.
[19] MOUSAVI N, TAN T C, ALI M, et al. Echocardiographic parameters of left ventricular size and function as predictors of symptomatic heart failure in patients with a left ventricular ejection fraction of 50-59% treated with anthracyclines[J]. Eur Heart J-Cardiovasc Imaging, 2015, 16(9): 977-984. DOI: 10.1093/ehjci/jev113.
[20] CARDINALE D, COLOMBO A, TORRISI R, et al. Trastuzumab-induced cardiotoxicity: clinical and prognostic implications of troponin I evaluation[J]. J Clin Oncol, 2010, 28(25): 3910-3916. DOI: 10.1200/jco.2009.27.3615.
[21] NAKANO S, TAKAHASHI M, KIMURA F, et al. Cardiac magnetic resonance imaging-based myocardial strain study for evaluation of cardiotoxicity in breast cancer patients treated with trastuzumab: a pilot study to evaluate the feasibility of the method[J]. Cardiol J, 2016, 23(3): 270-280. DOI: 10.5603/cj.a2016.0023.
[22] SWAIN S M, EWER M S, CORTÉS J, et al. Cardiac tolerability of pertuzumab plus trastuzumab plus docetaxel in patients with HER2-positive metastatic breast cancer in CLEOPATRA: a randomized, double-blind, placebo-controlled phase III study[J]. Oncol, 2013, 18(3): 257-264. DOI: 10.1634/theoncologist.2012-0448.
[23] 盛李明, 杜向慧. 乳腺癌患者赫赛汀相关心脏毒性机制及处理[J]. 中国临床药理学与治疗学, 2011, 16(9): 1077-1080.
[24] GOLDHIRSCH A, GELBER R D, PICCART-GEBHART M J, et al. 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer(HERA): an open-label, randomised controlled trial[J]. Lancet, 2013, 382(9897): 1021-1028. DOI: 10.1016/s0140-6736(13)61094-6.
[25] 刘倩欣, 向倩, 李晓颖, 等. 1例曲妥珠单抗导致的心脏毒性病例分析[J]. 临床药物治疗杂志, 2016, 14(5): 75-78. DOI: 10.3969/j.issn.1672-3384.2016.05.019.
[26] RYU M H, YOO C, KIM J G, et al. Multicenter phase Ⅱ study of trastuzumab in combination with capecitabine and oxaliplatin for advanced gastric cancer[J]. Eur J Cancer, 2015, 51(4): 482-488. DOI: 10.1016/j.ejca.2014.12.015.
[27] 蔡晔芬, 李佳, 王燕莉, 等. 曲妥珠单抗治疗HER2阳性晚期胃癌血液/骨髓药物不良反应的Meta分析[J]. 海峡药学, 2016, 28(12): 83-86.
[28] 刘小林, 符一岚, 朱秋燕, 等. 曲妥珠单抗致不良反应分析[J]. 药学与临床研究, 2017, 25(1): 63-66. DOI: 10.13664/j.cnki.pcr.2017.01.018.
[29] 赵冬梅, 陈静, 李晶, 等. 注射用曲妥珠单抗安全输注问题与建议[J]. 武警医学, 2016, 27(10): 1061-1063. DOI: 10.14010/j.cnki.wjyx.2016.10.031.
[30] TANZ R, MEILLAN N, LIBERT N, et al. Successful readministration of trastuzumab after severe immune reactions in two breast cancer patients[J]. Investig New Drugs, 2014, 32(3): 573-574. DOI: 10.1007/s10637-014-0085-6.
[31] 孙晓春. 583例曲妥珠单抗不良反应/不良事件文献分析[DB/OL].(2017-07-25)[2019-08-26]. http://med.wanfangdata.com.cn/Paper/Detail?id=ConferencePaper_9058387&dbid=WF_HY.
[32] 韩敏, 王坚, 郑玮薇. 曲妥珠单抗联合紫杉醇脂质体及卡培他滨对HER-2阳性复发转移性乳腺癌患者血清LCN-2及Sixl表达的影响[J]. 临床药物治疗杂志, 2018, 16(8): 26-34. DOI: 10.3969/j.issn.1672-3384.2018.08.006.
[33] 周宁, 刘翠云, 唐勇. DOX方案对比曲妥珠单抗联合DOX用于进展期胃癌新辅助治疗的疗效[J]. 实用药物与临床, 2017, 20(5): 512-516. DOI: 10.14053/j.cnki.ppcr.201705006.
[34] 董利森, 刘璐. 临床药师参与1例曲妥珠单抗致不良反应治疗方案的制定[J]. 中国药师, 2015, 18(12): 2112-2113.
[35] 景天闯. 曲妥珠单抗联合紫杉醇脂质体致呼吸衰竭病例分析[DB/OL].(2017-07-25)[2019-08-18]. http://med.wanfangdata.com.cn/Paper/Detail?id=ConferencePaper_9059104&dbid=WF_HY.
[36] COSTA R B, KURRA G, GREENBERG L, et al. Efficacy and cardiac safety of adjuvant trastuzumab-based chemotherapy regimens for HER2-positive early breast cancer[J]. Ann Oncol, 2010, 21(11): 2153-2160. DOI: 10.1093/annonc/mdq096.
[37] ISHIZUNA K, NINOMIYA J, OGAWA T, et al. Hepatotoxicity induced by trastuzumab used for breast cancer adjuvant therapy: a case report[J]. J Med Case Rep, 2014, 8: 417. DOI: 10.1186/1752-1947-8-417.
[38] 解染, 赵楠, 崔一民. 1例曲妥珠单抗致肝毒性的病例报告及药物不良反应分析[J]. 中国临床药理学杂志, 2017, 33(10): 936-938. DOI: 10.13699/j.cnki.1001-6821.2017.10.019.