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血液系统疾病相关心脏毒性:酪氨酸激酶抑制剂伊马替尼和尼罗替尼安全吗?

Cardiotoxicity in Hematological Diseases: Are the Tyrosine Kinase Inhibitors Imatinib and Nilotinib Safe?

机构信息

Cardiology Department, Faculty of Medicine, Santa Maria University Hospital (CHLN), Lisbon Academic Medical Centre and Cardiovascular Centre of the University of Lisbon, Av. Prof. Egas Moniz, 1649-035, Lisbon, Portugal.

Hematology Department, Faculty of Medicine, Santa Maria University Hospital (CHLN), Lisbon, Portugal.

出版信息

Cardiovasc Toxicol. 2018 Oct;18(5):431-435. doi: 10.1007/s12012-018-9453-3.

Abstract

Chemotherapy-induced cardiotoxicity is a growing concern. The cardiotoxic impact of new drugs such as tyrosine kinase inhibitors is unknown, especially the ones used for chronic myeloid leukemia. We aim to evaluate nilotinib- and imatinib-induced cardiotoxicity. Single-center prospective study of consecutive patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors was conducted during 2015. Patients underwent an initial clinical, laboratorial and echocardiographic evaluation, repeated after 1 year. Eleven patients were included [60.0 (11) years, 63.6% of males; seven patients treated with imatinib and four with nilotinib]. After 1 year of follow-up, all patients remained in functional NYHA class I, with a similar Minnesota quality of life score. Also there was no difference in the biomarkers evaluated (cystatin-C and NT-proBNP). Likewise, no modification in systolic or diastolic function evaluated by echocardiography was observed. All patients presented normal values of longitudinal, circumferential and radial strain in the baseline study, without changes during follow-up. In addition, there were no differences between the two tyrosine kinase inhibitors used, considering all the aforementioned variables. No clinical, laboratory or echocardiographic evidence of nilotinib- and imatinib-induced cardiotoxicity was observed. However, these results should be confirmed in multicenter studies given the low incidence of chronic myeloid leukemia.

摘要

化疗引起的心脏毒性是一个日益受到关注的问题。新型药物(如酪氨酸激酶抑制剂)的心脏毒性影响尚不清楚,特别是用于治疗慢性髓性白血病的药物。我们旨在评估尼洛替尼和伊马替尼引起的心脏毒性。

2015 年,我们进行了一项单中心前瞻性研究,纳入了接受酪氨酸激酶抑制剂治疗的慢性髓性白血病连续患者。患者接受了初始的临床、实验室和超声心动图评估,并在 1 年后重复评估。

11 名患者入组(年龄 60.0±11 岁,男性占 63.6%;7 名患者接受伊马替尼治疗,4 名患者接受尼洛替尼治疗)。随访 1 年后,所有患者仍保持纽约心脏协会(NYHA)心功能 I 级,明尼苏达生活质量评分相似。同时,所评估的生物标志物(胱抑素-C 和 NT-proBNP)也无差异。

同样,超声心动图评估的收缩和舒张功能也没有变化。所有患者在基线研究中均表现出正常的纵向、环向和径向应变值,随访期间无变化。此外,在考虑所有上述变量时,两种酪氨酸激酶抑制剂之间没有差异。

未观察到尼洛替尼和伊马替尼引起的心脏毒性的临床、实验室或超声心动图证据。然而,鉴于慢性髓性白血病的发病率较低,这些结果需要在多中心研究中得到证实。

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