Reversibility of trastuzumab-related cardiotoxicity: New insights based on clinical course and response to medical treatment
Reversibility of trastuzumab-related cardiotoxicity: New insights based on clinical course and response to medical treatment
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DOI：
10.1200/jco.2005.13.300
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发表时间：
2005-11-01
影响因子：
45.3
通讯作者：
Lenihan, DJ
中科院分区：
文献类型：
--
作者：
Ewer, MS;Vooletich, MT;Lenihan, DJ
目的曲妥珠单抗是一种重要的生物制剂，在HER2/neu标记过表达的乳腺癌中具有显著的活性。然而，曲妥珠单抗与心脏毒性有关，尚未得到充分研究。我们介绍了发生曲妥珠单抗相关心脏毒性的患者的经验。患者和方法在4年的时间里，38名HER2/neu阳性乳腺癌患者被转诊为怀疑曲妥珠单抗相关的心脏毒性。结果阿霉素治疗后曲妥珠单抗前左室射血分数(LVEF)平均(+/-标准差)为0.61+/-0.13，曲妥珠单抗后左室射血分数(LVEF)降至0.43+/-0.16(P<；0.0001)。停用曲妥珠单抗后，左心室射血分数增加至0.56+/-0.11。平均左心室射血分数恢复时间为1.5个月，在38例患者中，32例(84%)与药物治疗有关，但6例(16%)未经治疗。38例患者中有37例左心室射血分数增加。其中25名患者再次接受曲妥珠单抗治疗；3名患者有复发的左心功能不全，但22名患者(88%)没有。所有再次接受治疗的患者在再次接受曲妥珠单抗挑战时，都继续接受心力衰竭的治疗方案。9例患者接受了心内膜心肌活检。未见超微结构改变。结论曲妥珠单抗治疗期间出现心脏毒性的患者在撤药后一般会有所改善。曲妥珠单抗相关的心功能障碍的机制不同于蒽环类药物的心脏毒性，部分原因是缺乏类蒽环素样的超微结构改变。重新使用曲妥珠单抗可能适合一些以前经历过曲妥珠单抗相关心功能不全的患者。
Purpose Trastuzumab is an important biologic agent with significant activity in breast cancers that overexpress the HER2/neu marker. However, trastuzumab is associated with cardiotoxicity that has not yet been fully explored. We present our experience with patients who developed trastuzumab-related cardiotoxicity.Patients and Methods Over a 4-year period, 38 patients with HER2/neu-positive breast cancer were referred for suspected trastuzumab-related cardiotoxicity. All patients had previously received anthracycline-based chemotherapy.Results After doxorubicin but before trastuzumab, the mean (+/- standard deviation) left ventricular ejection fraction (LVEF) was 0.61 +/- 0.13, and the LVEF decreased to 0.43 +/- 0.16 after trastuzumab (P < .0001). After withdrawal of trastuzumab, the LVEF increased to 0.56 +/- 0.11. Mean time to recovery of LVEF was 1.5 months and was temporally associated with medical treatment in 32 (84%) of the 38 patients but occurred without treatment in six patients (16%). Increases in LVEF were noted in 37 of the 38 patients. Twenty-five of these patients were re-treated with trastuzumab; three patients had recurrent left ventricular dysfunction, but 22 patients (88%) did not. All re-treatment patients continued on their therapeutic regimen for heart failure when rechallenged with trastuzumab. Nine patients underwent endomyocardial biopsy. Ultrastructural changes were not seen.Conclusion Patients who develop cardiotoxicity while receiving trastuzumab therapy generally improve on removal of the agent. The mechanism of trastuzumab-related cardiac dysfunction is different from that of anthracycline cardiotoxicity, in part, demonstrated by the absence of anthracycline-like ultrastructural changes. Reintroducing trastuzumab may be appropriate for some individuals who previously have experienced trastuzumab-related cardiac dysfunction.