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尼洛替尼治疗慢性髓性白血病相关不良反应:机制与管理策略。

Adverse events associated with nilotinib in chronic myeloid leukemia: mechanisms and management strategies.

机构信息

Department of Colorectal Pharmacy, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Hangzhou, China.

Center for Drug Safety Evaluation and Research of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.

出版信息

Expert Rev Clin Pharmacol. 2021 Apr;14(4):445-456. doi: 10.1080/17512433.2021.1894129. Epub 2021 Feb 28.

DOI:10.1080/17512433.2021.1894129
PMID:33618586
Abstract

: Nilotinib is a second-generation tyrosine kinase inhibitor (TKI) targeting BCR/ABL, which is used for the first-line treatment of newly diagnosed chronic myeloid leukemia (CML) patients and the second-line treatment of most CML patients who are resistant or intolerant to prior therapy that includes imatinib. In addition to common adverse reactions, long-term use of nilotinib shows some toxicities that are different from those of occurring during other BCR/ABL TKI treatments, such as cardiovascular toxicity. It is life-threatening, which would affect not only the choice of initial treatment of CML patients but also the safety of long-term medication.: Through searching literature and reports from PubMed and clinical trials, here we review a profile of the adverse effects induced by nilotinib. We also discuss the potential molecular toxicological mechanisms and clinical management, which may provide strategies to prevent or intervene the toxicity associated with nilotinib.: Severe adverse effects associated with nilotinib limit its long-term clinical application. However, the exact mechanisms underlying these toxicities remain unclear. Future research should focus on the developing strategies to reduce the toxicities of nilotinib as well as to avoid similar toxicity in the development of new drugs.

摘要

尼洛替尼是一种针对 BCR/ABL 的第二代酪氨酸激酶抑制剂 (TKI),用于初诊慢性髓性白血病 (CML) 患者的一线治疗,以及对包括伊马替尼在内的既往治疗耐药或不耐受的大多数 CML 患者的二线治疗。除了常见的不良反应外,尼洛替尼的长期使用还表现出一些与其他 BCR/ABL TKI 治疗期间不同的毒性,如心血管毒性。它具有致命性,不仅会影响 CML 患者初始治疗的选择,还会影响长期用药的安全性。

通过检索文献和 PubMed 中的报告以及临床试验,我们在此综述了尼洛替尼引起的不良反应特征。我们还讨论了潜在的分子毒理学机制和临床管理,这可能为预防或干预与尼洛替尼相关的毒性提供策略。

与尼洛替尼相关的严重不良反应限制了其长期临床应用。然而,这些毒性的确切机制仍不清楚。未来的研究应集中于开发减少尼洛替尼毒性的策略,以及避免在新药开发中出现类似毒性。

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