CHU Caen, PICARO Cardio-oncology Program, Department of Pharmacology, F-14033 Caen, France; Normandie Univ, UNICAEN, CHU Caen, EA 4650, Signalisation, Électrophysiologie et Imagerie des Lésions d'Ischémie-Reperfusion Myocardique, 14000 Caen, France.
Vanderbilt University Medical Center, Cardio-oncology Program, Department of Medicine, Nashville, Tennessee, USA.
Pharmacol Ther. 2018 Sep;189:89-103. doi: 10.1016/j.pharmthera.2018.04.009. Epub 2018 Apr 24.
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.
癌症治疗的显著进展已经降低了许多恶性肿瘤的癌症相关死亡率，一些癌症类型现在被认为是慢性病。尽管取得了这些进展，但越来越多的人认识到，许多癌症患者或癌症幸存者可能会患上心血管疾病，这要么是由于癌症本身，要么是由于抗癌治疗的结果。人们非常关注心力衰竭；然而，其他心脏毒性，特别是心律失常，也可能在没有潜在心肌病的情况下发生。在接受细胞毒性化疗（蒽环类药物、吉西他滨、顺铂和烷化剂）或激酶抑制剂（如伊布替尼）治疗的癌症患者中会发生室上性心动过速。已经报道了一些心律失常，其中一些是尖端扭转型室性心动过速（TdP），由 QTc 延长引起：这可能是直接抑制 hERG 通道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激酶抑制剂、三氧化二砷、蒽环类药物、组蛋白去乙酰化酶抑制剂和选择性雌激素受体调节剂。即使是经验丰富的临床医生，也仍然低估了抗癌药物引起的心律失常这一并发症。此外，由于患者的合并症和复杂的治疗方案，特定抗癌药物与心律失常发生之间的因果关系仍然具有挑战性。例如，任何癌症患者也可能被诊断出患有常见疾病，如高血压、糖尿病或心力衰竭，这些疾病会增加个体发生心律失常的易感性。此外，抗癌药物通常联合使用，这增加了确定因果关系的难度。因此，心律失常似乎是抗癌药物的一种被低估的不良反应，其发生率、意义和潜在机制正在被研究。
