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曲妥珠单抗恩美曲妥珠单抗(T-DM1)治疗HER2阳性乳腺癌患者的不良事件

Adverse Events of Trastuzumab Emtansine (T-DM1) in the Treatment of HER2-Positive Breast Cancer Patients.

作者信息

Kowalczyk Lidia, Bartsch Rupert, Singer Christian F, Farr Alex

机构信息

Clinical Unit of Anesthesiology and Perioperative Intensive-Care Medicine, University of Veterinary Medicine, Vienna, Austria.

Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria.

出版信息

Breast Care (Basel). 2017 Dec;12(6):401-408. doi: 10.1159/000480492. Epub 2017 Dec 3.

Abstract

The human epidermal growth factor receptor 2 (HER2) is commonly associated with poor prognosis and is overexpressed in approximately 15-20% of all breast cancers. The introduction of HER2-targeted therapies led to significant improvement in the prognosis of patients with HER2-positive breast cancer, for both early and advanced disease. These targeted therapies include the antibodies trastzumab and pertuzumab, the tyrosine kinase inhibitor lapatinib, and the antibody-drug conjugate trastuzumab emtansine (T-DM1). T-DM1 combines the anti-tumor activity of trastuzumab with that of DM1, a highly potent derivative of the anti-microtubule agent maytansine, resulting in increased anti-tumor activity. Notably, this agent has been demonstrated to be safe and is associated with low toxicity rates. However, maytansinoid, the cytotoxic component of T-DM1, does have the potential to induce various adverse events, particularly radiation necrosis, when used in combination with stereotactic radiosurgery. In this review, we aimed to summarize the current literature regarding T-DM1 safety and toxicity, with special emphasis on the existing landmark studies.

摘要

人表皮生长因子受体2(HER2)通常与预后不良相关,在所有乳腺癌中约15%-20%呈过表达。HER2靶向治疗的引入显著改善了HER2阳性乳腺癌患者的预后,无论是早期还是晚期疾病。这些靶向治疗包括抗体曲妥珠单抗和帕妥珠单抗、酪氨酸激酶抑制剂拉帕替尼以及抗体药物偶联物曲妥珠单抗 emtansine(T-DM1)。T-DM1将曲妥珠单抗的抗肿瘤活性与DM1(抗微管药物美登素的高效衍生物)的抗肿瘤活性相结合,从而增强了抗肿瘤活性。值得注意的是,该药物已被证明是安全的,且毒性率较低。然而,T-DM1的细胞毒性成分美登素类药物在与立体定向放射外科联合使用时,确实有可能引发各种不良事件,尤其是放射性坏死。在本综述中,我们旨在总结当前关于T-DM1安全性和毒性的文献,特别强调现有的标志性研究。

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