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Anticancer drug-induced cardiac rhythm disorders: Current knowledge and basic underlying mechanisms
Pharmacology & Therapeutics ( IF 12.0 ) Pub Date : 2018-04-24 , DOI: 10.1016/j.pharmthera.2018.04.009
Joachim Alexandre , Javid J. Moslehi , Kevin R. Bersell , Christian Funck-Brentano , Dan M. Roden , Joe-Elie Salem

Significant advances in cancer treatment have resulted in decreased cancer related mortality for many malignancies with some cancer types now considered chronic diseases. Despite these improvements, there is increasing recognition that many cancer patients or cancer survivors can develop cardiovascular diseases, either due to the cancer itself or as a result of anticancer therapy. Much attention has focused on heart failure; however, other cardiotoxicities, notably cardiac rhythm disorders, can occur without underlying cardiomyopathy.

Supraventricular tachycardias occur in cancer patients treated with cytotoxic chemotherapy (anthracyclines, gemcitabine, cisplatin and alkylating-agents) or kinase-inhibitors (KIs) such as ibrutinib. Ventricular arrhythmias, with a subset of them being torsades-de-pointes (TdP) favored by QTc prolongation have been reported: this may be the result of direct hERG-channel inhibition or a more recently-described mechanism of phosphoinositide-3-kinase inhibition. The major anticancer drugs responsible for QTc prolongation in this context are KIs, arsenic trioxide, anthracyclines, histone deacetylase inhibitors, and selective estrogen receptor modulators.

Anticancer drug-induced cardiac rhythm disorders remain an underappreciated complication even by experienced clinicians. Moreover, the causal relationship of a particular anticancer drug with cardiac arrhythmia occurrence remains challenging due in part to patient comorbidities and complex treatment regimens. For example, any cancer patient may also be diagnosed with common diseases such as hypertension, diabetes or heart failure which increase an individual's arrhythmia susceptibility. Further, anticancer drugs are generally usually used in combination, increasing the challenge around establishing causation.

Thus, arrhythmias appear to be an underappreciated adverse effect of anticancer agents and the incidence, significance and underlying mechanisms are now being investigated.



中文翻译:

抗癌药诱发的心律失常:最新知识和基本潜在机制

癌症治疗的重大进展已导致许多恶性肿瘤的癌症相关死亡率降低,而某些恶性肿瘤现已被视为慢性疾病。尽管有这些改进,但人们越来越认识到,许多癌症患者或癌症幸存者仍可能由于癌症本身或由于抗癌疗法而患上心血管疾病。很多注意力都集中在心力衰竭上。但是,在没有潜在的心肌病的情况下,也可能发生其他心脏毒性反应,尤其是心律失常。

室上性心动过速发生在接受细胞毒性化学疗法(蒽环类,吉西他滨,顺铂和烷化剂)或激酶抑制剂(KIs)(如依鲁替尼)治疗的癌症患者中。室性心律失常,其中的一部分为QTc延长所致​​的扭转性扭转(TdP),已有报道:这可能是直接的hERG通道抑制或最近描述的磷酸肌醇-3-激酶抑制机制的结果。 。在这种情况下,导致QTc延长的主要抗癌药物是KIs,三氧化二砷,蒽环类,组蛋白脱乙酰基酶抑制剂和选择性雌激素受体调节剂。

即使是有经验的临床医生,抗癌药诱发的心律失常仍未引起人们的重视。此外,部分由于患者合并症和复杂的治疗方案,特定抗癌药物与心律不齐的发生之间的因果关系仍然具有挑战性。例如,任何癌症患者也可以被诊断出患有常见疾病,例如高血压,糖尿病或心力衰竭,这些疾病会增加个体的心律不齐的易感性。此外,抗癌药通常通常组合使用,增加了建立因果关系的挑战。

因此,心律不齐似乎是抗癌药的一种被低估的不良反应,目前正在研究其发生率,意义和潜在机制。

更新日期:2018-04-24
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