First-Line Trastuzumab Plus Epirubicin and Cyclophosphamide Therapy in Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer: Cardiac Safety and Efficacy Data From the Herceptin, Cyclophosphamide, and Epirubicin (HERCULES) Trial
First-Line Trastuzumab Plus Epirubicin and Cyclophosphamide Therapy in Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer: Cardiac Safety and Efficacy Data From the Herceptin, Cyclophosphamide, and Epirubicin (HERCULES) Trial
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DOI：
10.1200/jco.2009.21.9709
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发表时间：
2010-03-20
影响因子：
45.3
通讯作者：
Lueck, Hans-Joachim
中科院分区：
文献类型：
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作者：
Untch, Michael;Muscholl, Michael;Lueck, Hans-Joachim
转移性乳腺癌（MBC）患者接受以阿霉素为基础的化疗和曲妥珠单抗治疗后，充血性心力衰竭（CHF）的发生率较高。赫赛汀，环磷酰胺，和Epiradine（HERCULES）试验评估曲妥珠单抗加环磷酰胺和心脏毒性较低的蒽环类epiradine.Patients和MethodsThis前瞻性试验相结合的第一阶段剂量发现阶段与第二阶段随机化阶段。总共有120例人表皮生长因子受体2（HER 2）阳性MBC和心脏功能良好的患者接受了一线曲妥珠单抗治疗。（4 mg/kg静脉负荷剂量，然后每周2 mg/kg）加环磷酰胺（600 mg/m2）和表阿霉素60 mg/m2（HEC-60）或90 mg/m2（HEC-90），共6个周期，随后进行曲妥珠单抗单药治疗直至进展。60例HER 2阴性疾病患者接受了表阿霉素（90 mg/m2）和环磷酰胺（EC-90）单药治疗。主要终点是剂量限制性心脏毒性（DLC）。结果DLC的发生率分别为5.0%，1.7%和0%，HEC-90，HEC-60，EC-90武器，分别。所有DLC事件均可控。无心脏相关死亡。除发热性中性粒细胞减少症外，其他不良事件特征在三个治疗组中相当，HEC-90治疗组中有10%的患者报告了发热性中性粒细胞减少症，而其他治疗组中有3%的患者报告了发热性中性粒细胞减少症。肿瘤反应率分别为57%，60%，和25%的HEC-60，HEC-90，EC-90武器，分别为中位时间进展为12.5，10.1，和7.6个月，分别为conclusionThe HEC方案是一个有前途的治疗方案，为患者与HER 2阳性MBC。与曲妥珠单抗+多柔比星相关的历史发生率相比，HEC的DLC发生率较低，支持进一步评价该方案，尤其是在辅助或新辅助治疗环境中。
PurposeA high incidence of congestive heart failure (CHF) has been observed in patients with metastatic breast cancer (MBC) receiving doxorubicin-based chemotherapy and trastuzumab. The Herceptin, Cyclophosphamide, and Epirubicin (HERCULES) trial evaluated trastuzumab plus cyclophosphamide and the less cardiotoxic anthracycline epirubicin.Patients and MethodsThis prospective trial combined a phase I dose-finding stage with a phase II randomized stage. In total, 120 patients with human epidermal growth factor receptor 2 (HER2) -positive MBC and adequate cardiac function received first-line trastuzumab (4 mg/kg intravenous loading dose, then 2 mg/kg every week) plus cyclophosphamide (600 mg/m(2)) and either epirubicin 60 mg/m(2) (HEC-60) or 90 mg/m(2) (HEC-90) for six cycles, followed by trastuzumab monotherapy until progression. Sixty patients with HER2-negative disease received epirubicin (90 mg/m(2)) and cyclophosphamide (EC-90) alone. The primary end point was dose-limiting cardiotoxicity (DLC).ResultsIncidence of DLC was 5.0%, 1.7%, and 0% in the HEC-90, HEC-60, and EC-90 arms, respectively. All DLC events were manageable. There were no cardiac-related deaths. Other adverse-event profiles were comparable across the three arms, except febrile neutropenia, which was reported in 10% of the HEC-90 arm compared with 3% of the other arms. Tumor response rates were 57%, 60%, and 25% in the HEC-60, HEC-90, and EC-90 arms, respectively; median time to progression was 12.5, 10.1, and 7.6 months, respectively.ConclusionThe HEC regimen is a promising treatment option for patients with HER2-positive MBC. The lower incidence of DLC with HEC, compared with the historic incidence associated with trastuzumab plus doxorubicin, supports further evaluation of the regimen, especially in adjuvant or neoadjuvant settings.