Cardiac dysfunction in the trastuzumab clinical trials experience
Cardiac dysfunction in the trastuzumab clinical trials experience
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DOI：
10.1200/jco.20.5.1215
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发表时间：
2002-03-01
影响因子：
45.3
通讯作者：
Keefe, D
中科院分区：
文献类型：
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作者：
Seidman, A;Hudis, C;Keefe, D
目的.本研究旨在估计接受曲妥珠单抗治疗的患者的心功能不全（CD）风险;根据严重程度、治疗和临床结局描述观察到的CD特征;评估基线临床风险因素对CD的影响;并评估累积剂量的蒽环类药物和曲妥珠单抗对CD的影响。患者和方法回顾性分析7项II期和III期曲妥珠单抗临床试验中任何一项的患者记录被执行。使用预先定义的标准进行诊断，并使用纽约心脏协会功能分类系统记录CD严重程度。产品的限制估计被用来总结累计蒽环类抗生素和曲妥珠单抗剂量在CD onset.Results的时间：曲妥珠单抗治疗的患者被发现是在CD的风险增加。在接受曲妥珠单抗和蒽环类药物+环磷酰胺合并治疗的患者中，发生率最高（27%）。接受紫杉醇和曲妥珠单抗（13%）或曲妥珠单抗单药（3%-7%）治疗的患者的风险显著降低;然而，这些患者中的大多数既往接受过蒽环类药物治疗。在接受蒽环类药物加环磷酰胺治疗的患者中，8%的患者出现CD，而接受紫杉醇单药治疗的患者中，1%的患者出现CD。大多数曲妥珠单抗治疗的CD患者有症状（75%），最改善充血性心力衰竭的标准治疗（79%）。结论：曲妥珠单抗与CD的风险增加，这是最大的并发接受蒽环类药物的患者。在大多数转移性乳腺癌患者中，考虑到既往报告的曲妥珠单抗治疗的总生存期改善，CD风险是合理的。(C)2002年，美国临床肿瘤学会。
Purpose. This study sought to estimate cardiac dysfunction (CD) risk for patients receiving trastuzurnab; to characterize observed CD by severity, treatment, and clinical outcome; to assess effects of baseline clinical risk factors on CD; and to assess effects of cumulative doses of anthracyclines and trostuzumab on CD.Patients and Methods A retrospective review of records for patients enrolled onto any of seven phase II and III trastuzumob clinical trials was performed. Predefined criteria were used for the diagnosis, and the New York Heart Association functional classification system was used to document CD severity. Product-limit estimates were used to summarize the cumulative anthracycline and trastuzurnab doses at the time of CD onset.Results: Patients treated with trastuzurnab were found to be at an increased risk for CD. The incidence was greatest in patients receiving concomitant trastuzumab and anthracycline plus cyclophosphamide (27%). The risk was substantially lower in patients receiving paclitaxel and trastuzumab (13%) or trastuzurnab alone (3% to 7%); however, most of these patients had received prior anthracycline therapy. CD was noted in 8% of patients receiving anthracycline plus cyclophosphamide and 1% receiving paclitaxel alone. Most trastuzurnab-treated patients developing CD were symptomatic (75%), and most improved with standard treatment for congestive heart failure (79%).Conclusion: Trastuzumab is associated with an increased risk of CD, which is greatest in patients receiving concurrent anthracyclines. In most patients with metastatic breast cancer, the risk of CD can be justified given the improvement in overall survival previously reported with trastuzumab. (C) 2002 by American Society of Clinical Oncology.