PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. 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.
PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. 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.
Authors: Eduardo Sanabria-Figueroa; Siobhan M Donnelly; Kevin C Foy; Meghan C Buss; Robert C Castellino; Elisavet Paplomata; Latonia Taliaferro-Smith; Pravin T P Kaumaya; Rita Nahta Journal: Mol Pharmacol Date: 2014-11-12 Impact factor: 4.436
Authors: Smitha Reddy; Calvin C Shaller; Mohan Doss; Irina Shchaveleva; James D Marks; Jian Q Yu; Matthew K Robinson Journal: Clin Cancer Res Date: 2010-12-21 Impact factor: 12.531
Authors: Heidrun Karlic; Harald Herrmann; Axel Schulenburg; Thomas W Grunt; Sylvia Laffer; Irina Mirkina; Rainer Hubmann; Medhat Shehata; Brigitte Marian; Edgar Selzer; Michael Pfeilstöcker; Elisabeth Pittermann; Ulrich Jäger; Hubert Pehamberger; Christoph Zielinski; Peter Valent Journal: Wien Klin Wochenschr Date: 2010-07-22 Impact factor: 1.704