Cardiology Service, Hospital of Santa Maria, University Clinic of Cardiology, Lisbon, Portugal.
Adv Ther. 2009 Jul;26 Suppl 1:S9-17. doi: 10.1007/s12325-009-0048-z. Epub 2009 Jul 24.
Although having high clinical efficacy in the treatment of human epidermal growth factor receptor-2 (HER2+) metastatic breast cancer, trastuzumab has been associated with cardiotoxicity, and the etiology and pathogenesis of this condition is currently under investigation.
This paper reviews the cardiotoxicity, associated with trastuzumab use and discusses the risk assessment and management of cardiac dysfunction.
The increased risk of cardiotoxicity is lower when trastuzumab is given as monotherapy (3%-7%) compared with anthracyclines + trastuzumab therapy (27%). Type II cardiac changes occur in trastuzumab-treated patients, which do not appear to be dose-related, are not associated with histological changes, and are generally reversible. Several risk factors for cardiac events have been identified and assessing levels of troponin I and N-terminal pro-brain B-type natriuretic peptide before and after treatment with trastuzumab may allow early detection of cardiotoxicity. A symptomatic and functional evaluation scheme for patients indicated for treatment with trastuzumab has also been proposed to work alongside therapeutic options for the treatment of heart failure.
The risk of cardiac dysfunction associated with trastuzumab can be justified given the increase in overall survival. This risk is lower when trastuzumab is given as monotherapy. The paradigm for cardiologists remains the same: treat the cancer effectively whilst preventing cardiotoxicity.
曲妥珠单抗在治疗人表皮生长因子受体-2(HER2+)转移性乳腺癌方面具有很高的临床疗效,但与心脏毒性相关,其病因和发病机制目前正在研究中。
本文综述了曲妥珠单抗相关的心脏毒性,并讨论了心脏功能障碍的风险评估和管理。
与蒽环类药物+曲妥珠单抗治疗(27%)相比,曲妥珠单抗单药治疗(3%-7%)的心脏毒性风险增加较低。曲妥珠单抗治疗患者出现 II 型心脏改变,似乎与剂量无关,与组织学改变无关,且通常是可逆的。已经确定了几个心脏事件的风险因素,在使用曲妥珠单抗治疗前后检测肌钙蛋白 I 和 N 末端脑利钠肽前体的水平可能有助于早期发现心脏毒性。还提出了一种针对曲妥珠单抗治疗适应证患者的症状和功能评估方案,以配合心力衰竭的治疗选择。
鉴于总生存期的增加,曲妥珠单抗相关心脏功能障碍的风险是合理的。当曲妥珠单抗单药治疗时,这种风险较低。心脏病专家的范例仍然不变:既要有效地治疗癌症,又要预防心脏毒性。