Bansal Neha, Amdani Shahnawaz, Lipshultz Emma R, Lipshultz Steven E
a Department of Pediatrics , Wayne State University School of Medicine and Children's Hospital of Michigan , Detroit , MI , USA.
c Department of Pediatric Oncology , Dana-Farber Cancer Institute , Boston , MA , USA.
Expert Opin Drug Metab Toxicol. 2017 Aug;13(8):817-832. doi: 10.1080/17425255.2017.1351547. Epub 2017 Jul 13.
With advances in clinical oncology, the burden of morbidity and mortality for cancer survivors due to the cardiac side effects of the chemotherapy is steadily increasing. Treatment-related cardiac damage is progressive and often irreversible. Primary prevention of cardiotoxicity during treatment is possible with strategies like limiting the cumulative anthracycline dose, the use of anthracycline structural analogs, and especially cardioprotective agents. Areas covered: This review covers the various cardiotoxic chemotherapeutic agents, the pathophysiology of cardiotoxicity due to anthracyclines, and the clinical and subclinical presentations and progression of childhood anthracycline cardiotoxicity. We also discuss preventive measures and strategies, especially the cardioprotectant agent dexrazoxane where there is strong evidence-based support for its use with anthracycline chemotherapy. However, there is a paucity of evidence-based recommendations for diagnosing and treating cancer therapy-induced cardiovascular complications. Finally, we discuss the potential of cardio-oncology. Expert opinion: There is no 'safe' anthracycline dose if the goal is normal long-term cardiovascular status but higher lifetime cumulative doses of anthracyclines, higher dose rates, female sex, longer follow-up, younger age at anthracycline treatment, pre-existing cardiovascular disease, and cardiac irradiation are associated with more severe cardiotoxicity. With deeper understanding of the mechanisms of the adverse cardiac effects and identification of driver mutations causing these effects, personalized cancer therapy to limit cardiotoxic effects can be achieved, such as with the cardioprotectant dexrazoxane.
随着临床肿瘤学的进展，癌症幸存者因化疗的心脏副作用而导致的发病和死亡负担正在稳步增加。与治疗相关的心脏损伤是渐进性的，且往往不可逆转。在治疗期间，通过限制蒽环类药物的累积剂量、使用蒽环类药物结构类似物，尤其是心脏保护剂等策略，可以对心脏毒性进行一级预防。涵盖领域：本综述涵盖了各种具有心脏毒性的化疗药物、蒽环类药物导致心脏毒性的病理生理学，以及儿童蒽环类药物心脏毒性的临床和亚临床表现及进展。我们还讨论了预防措施和策略，特别是心脏保护剂右丙亚胺，有强有力的循证支持其与蒽环类化疗联合使用。然而，对于癌症治疗引起的心血管并发症的诊断和治疗，缺乏基于证据的建议。最后，我们讨论了心脏肿瘤学的潜力。专家观点：如果目标是长期保持正常心血管状态，那么不存在“安全”的蒽环类药物剂量，但蒽环类药物的终身累积剂量越高、给药速率越高、女性、随访时间越长、蒽环类药物治疗时年龄越小、既往有心血管疾病以及接受过心脏放疗，与更严重的心脏毒性相关。随着对不良心脏效应机制的更深入理解以及对导致这些效应的驱动突变的识别，可以实现限制心脏毒性效应的个性化癌症治疗，例如使用心脏保护剂右丙亚胺。
