Pathophysiology of cardiotoxicity induced by nonanthracycline chemotherapy
Pathophysiology of cardiotoxicity induced by nonanthracycline chemotherapy
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DOI：
10.2459/jcm.0000000000000376
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发表时间：
2016-05-01
影响因子：
3
通讯作者：
Mercuro, Giuseppe
中科院分区：
文献类型：
--
作者：
Madeddu, Clelia;Deidda, Martino;Mercuro, Giuseppe
化疗引起的心脏毒性(CTX)的风险和机制因抗癌方案的类型和强度而异。无数的化疗药物会产生不良的心血管效应，如动脉高血压、心力衰竭和血栓栓子事件。在这些药物的众多类别中，由于其明显的心血管作用和高相关的心力衰竭发生率，蒽环类药物得到了最广泛的研究。然而，CTX也可能由其他类型的化疗药物引起，包括烷基化药物(环磷酰胺、异环磷酰胺)、铂类药物、抗代谢药物(5-氟尿嘧啶、卡培他滨)、抗生素(米托蒽醌、丝裂霉素、博莱霉素)和抗微管药物(紫杉烷)。在这里，我们回顾了环磷酰胺的发病率，临床影响，和潜在的机制，与非蒽环类药物化疗用于癌症患者。公布的数据支持CTX风险显著增加，特别是某些药物，如5-氟尿嘧啶和顺铂。每种抗癌方案都与不同的心脏损害模式有关，包括有症状和无症状。然而，CTX的潜在机制仅在少数病例中建立，并且只有少数非蒽环类化疗药物(米托蒽酮、丝裂霉素、异环磷酰胺)通过可识别的机制起作用，并显示出可预测的剂量依赖关系。最后，非蒽环类药物化疗既可导致慢性损害，如收缩功能障碍，也可导致急性损害，如治疗后数小时或数天内发生的缺血。显然，需要更多地了解由各种非蒽环类化疗药物引起的CTX的发生率、机制和潜在的治疗靶点。
The risk and mechanism of chemotherapy-induced cardiotoxicity (CTX) vary depending on the type and intensity of the anticancer regimen. Myriad chemotherapeutic drugs produce adverse cardiovascular effects such as arterial hypertension, heart failure, and thromboembolic events. Among the numerous classes of these drugs, anthracyclines have been studied most extensively because of their overt cardiovascular effects and the high associated incidence of heart failure. However, CTX might also be caused by other types of chemotherapeutic agents, including alkylating agents (cyclophosphamide, ifosfamide), platinum agents, antimetabolites (5-fluorouracil, capecitabine), antibiotics (mitoxantrone, mitomycin, bleomycin), and antimicrotubule agents (taxanes). Here, we review the incidence, clinical impact, and potential mechanisms of CTX associated with nonanthracycline chemotherapy used for cancer patients. The published data support a marked increase in CTX risk, particularly with certain drugs such as 5-fluorouracil and cisplatin. Each anticancer regimen is associated with distinct modes of heart damage, both symptomatic and asymptomatic. However, the underlying mechanisms of CTX have been established only in a few cases, and only few nonanthracycline chemotherapeutics (mitoxantrone, mitomycin, ifosfamide) act through a recognizable mechanism and show a predictable dose dependence. Lastly, nonanthracycline chemotherapy can induce both chronic lesions, such as systolic dysfunction, and acute lesions, such as the ischemia that occurs within hours or days after treatment. An increased understanding of the incidence, mechanisms, and potential therapeutic targets of CTX induced by various nonanthracycline chemotherapeutic agents is clearly required.