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慢性髓性白血病靶向治疗的心血管并发症

Cardiovascular Complications of Targeted Therapies for Chronic Myeloid Leukemia.

作者信息

Damrongwatanasuk Rongras, Fradley Michael G

机构信息

Cardio-Oncology Program, Division of Cardiovascular Medicine, University of South Florida and H. Lee Moffitt Cancer Center & Research Institute, 2 Tampa General Circle, Tampa, FL, 33606, USA.

出版信息

Curr Treat Options Cardiovasc Med. 2017 Apr;19(4):24. doi: 10.1007/s11936-017-0524-8.

DOI:10.1007/s11936-017-0524-8
PMID:28316033
Abstract

The development of tyrosine kinase inhibitors (TKIs) dramatically changed the treatment landscape for many different cancers including chronic myeloid leukemia (CML). With the introduction of imatinib, the first TKI developed and approved to effectively treat CML, patient survival has increased dramatically and, in some cases, this fatal cancer can be managed as a chronic disease. Since the approval of imatinib in 2002, four additional TKIs have been developed to treat this disease including the second-generation TKIs nilotinib, dasatinib, and bosutinib and the third-generation TKI ponatinib. Despite their significant impact on the progression of CML, there is increasing recognition of cardiovascular toxicities which can limit their long-term use and impact patient morbidity and mortality. The majority of the cardiotoxicities are associated with the second- and third-generation TKIs, the most concerning of which are vascular events including myocardial infarction, stroke and peripheral arterial disease. In addition, QT prolongation, pleural effusions, and both systemic and pulmonary hypertension are also observed. It is essential for both cardiologists and oncologists to possess knowledge of these issues in order to develop appropriate monitoring and risk mitigation strategies to prevent these toxicities and avoid premature cessation of the drug.

摘要

酪氨酸激酶抑制剂(TKIs)的发展极大地改变了包括慢性髓性白血病(CML)在内的多种不同癌症的治疗格局。随着首个研发并获批用于有效治疗CML的TKI伊马替尼的引入,患者生存率大幅提高,在某些情况下,这种致命癌症可作为慢性病进行管理。自2002年伊马替尼获批以来,又研发了另外四种TKI用于治疗该疾病,包括第二代TKI尼罗替尼、达沙替尼和博舒替尼以及第三代TKI普纳替尼。尽管它们对CML的进展有重大影响,但人们越来越认识到心血管毒性,这可能会限制它们的长期使用,并影响患者的发病率和死亡率。大多数心脏毒性与第二代和第三代TKI有关,其中最令人担忧的是血管事件,包括心肌梗死、中风和外周动脉疾病。此外,还观察到QT间期延长、胸腔积液以及全身性和肺动脉高压。心脏病专家和肿瘤学家都必须了解这些问题,以便制定适当的监测和风险缓解策略,以预防这些毒性并避免过早停药。

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