Phase II study of weekly docetaxel and trastuzumab for patients with HER-2-overexpressing metastatic breast cancer
Phase II study of weekly docetaxel and trastuzumab for patients with HER-2-overexpressing metastatic breast cancer
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DOI：
10.1200/jco.2002.07.058
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发表时间：
2002-04-01
影响因子：
45.3
通讯作者：
Hortobagyi, GN
中科院分区：
文献类型：
--
作者：
Esteva, FJ;Valero, V;Hortobagyi, GN
目的：评价每周一次多西紫杉醇联合曲妥昔单抗治疗HER-2过表达的转移性乳腺癌的安全性和有效性。疗效与血清HER-2胞外区(ECD)水平相关。患者和方法：30例转移性乳腺癌患者接受每周一次的多西紫杉醇联合曲妥昔单抗治疗，作为一线或二线治疗。多西紫杉醇35 mg/m(2)/wk和曲妥昔单抗2 mg/kg/wk均以4周为周期给药，每周治疗3次，休息1周。结果：多西紫杉醇的中位给药剂量强度为24 mg/m(2)/wk(范围为27 mg/m(2)/wk)。意向治疗总有效率(ORR)为63%(95%可信区间[CI]，44%~80%)。HER-2荧光原位杂交阳性患者ORR为67%(16/24，95%CI，45%~84%)。在基线水平HER-2 ECD升高的患者中，ORR为76%(95%CI，53%~92%)，而在HER-2ECD水平较低的患者中，ORR为33%(95%CI，7%~70%)(P=0.04)。治疗期间HER-2 ECD浓度的变化与治疗反应相关。中位进展时间为9个月。急性毒性，包括骨髓抑制，是轻微的。随着重复给药，疲乏、液体滞留和过度流泪变得更加常见。结论：每周一次的多西紫杉醇联合曲妥珠单抗是治疗HER-2过度表达的转移性乳腺癌的有效组合。血清HER-2 ECD检测可能是监测曲妥珠单抗治疗患者的一种有前途的方法。(C)2002年，由美国临床肿瘤学会提供。
Purpose: To evaluate the safety and efficacy of weekly docetaxel plus trastuxumab in women with HER-2-overexpressing metastatic breast cancer. Efficacy was correlated with serum HER-2 extracellular domain (ECD) levels.Patients and Methods: Thirty women with metastatic breast cancer were treated with weekly docetaxel and trastuxumab as first- or second-line therapy. Both docetaxel 35 mg/m(2)/wk and trastuxumab 2 mg/kg/wk were delivered in 4-week cycles consisting of three weekly treatments followed by 1 week of rest. A loading dose of trastuxumab 4 mg/kg was administered I day before the start of the first cycle.Results: The median delivered dose-intensity of docetaxel was 24 mg/m(2)/wk (range, IS to 27 mg/m(2)/wk). The intent-to-treat overall response rate (ORR) was 63% (95% confidence interval [Cl], 44% to 80%). The ORR in patients whose tumors were HER-2-positive by fluorescence in situ hybridization was 67% (16 of 24 patients, 95% Cl, 45% to 84%). In patients with elevated serum HER-2 ECD at baseline, the ORR was 76% (95% Cl, 53% to 92%), compared with 33% (95% Cl, 7% to 70%) in patients with low HER-2 ECD levels (P = .04). Variations in HER-2 ECD concentrations during treatment correlated with response to treatment. Median time to progression was 9 months. Acute toxicity, including myelosuppression, was mild. Fatigue, fluid retention, and excessive tearing became more common with repetitive dosing.Conclusion: Weekly docetaxel and trastuzumab is an active combination for treating patients with HER-2-overexpressing metastatic breast cancer. Serum HER-2 ECD testing may be a promising method for monitoring patients on trastuzumab-based therapy. (C) 2002 by American Society of Clinical Oncology.