Esteva Francisco J, Valero Vicente, Booser Daniel, Guerra Laura T, Murray James L, Pusztai Lajos, Cristofanilli Massimo, Arun Banu, Esmaeli Bita, Fritsche Herbert A, Sneige Nour, Smith Terry L, Hortobagyi Gabriel N
Department of Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
J Clin Oncol. 2002 Apr 1;20(7):1800-8. doi: 10.1200/JCO.2002.07.058.
To evaluate the safety and efficacy of weekly docetaxel plus trastuzumab in women with HER-2-overexpressing metastatic breast cancer. Efficacy was correlated with serum HER-2 extracellular domain (ECD) levels.
Thirty women with metastatic breast cancer were treated with weekly docetaxel and trastuzumab as first- or second-line therapy. Both docetaxel 35 mg/m(2)/wk and trastuzumab 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 trastuzumab 4 mg/kg was administered 1 day before the start of the first cycle.
The median delivered dose-intensity of docetaxel was 24 mg/m(2)/wk (range, 18 to 27 mg/m(2)/wk). The intent-to-treat overall response rate (ORR) was 63% (95% confidence interval [CI], 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% CI, 45% to 84%). In patients with elevated serum HER-2 ECD at baseline, the ORR was 76% (95% CI, 53% to 92%), compared with 33% (95% CI, 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.
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.
评估每周使用多西他赛联合曲妥珠单抗治疗HER-2过表达转移性乳腺癌女性患者的安全性和疗效。疗效与血清HER-2细胞外结构域（ECD）水平相关。
30例转移性乳腺癌女性患者接受每周一次多西他赛和曲妥珠单抗治疗，作为一线或二线治疗方案。多西他赛35mg/m²/周和曲妥珠单抗2mg/kg/周均以4周为一个周期给药，包括每周3次治疗，随后休息1周。在第一个周期开始前1天给予曲妥珠单抗4mg/kg的负荷剂量。
多西他赛的中位给药剂量强度为24mg/m²/周（范围为18至27mg/m²/周）。意向性治疗的总缓解率（ORR）为63%（95%置信区间[CI]，44%至80%）。通过荧光原位杂交检测肿瘤为HER-2阳性的患者的ORR为67%（24例患者中的16例；95%CI，45%至84%）。基线时血清HER-2 ECD升高的患者的ORR为76%（95%CI，53%至92%），而HER-2 ECD水平低的患者为33%（95%CI，7%至70%）（P = 0.04）。治疗期间HER-2 ECD浓度的变化与治疗反应相关。中位疾病进展时间为9个月。急性毒性，包括骨髓抑制，较轻。随着重复给药，疲劳、液体潴留和流泪变得更加常见。
每周使用多西他赛和曲妥珠单抗是治疗HER-2过表达转移性乳腺癌患者的有效联合方案。血清HER-2 ECD检测可能是监测接受曲妥珠单抗治疗患者的一种有前景的方法。
