Weekly trastuzumab and paclitaxel therapy for metastatic breast cancer with analysis of efficacy by HER2 immunophenotype and gene amplification Journal Article

Authors: Seidman, A. D.; Fornier, M. N.; Esteva, F. J.; Tan, L.; Kaptain, S.; Bach, A.; Panageas, K. S.; Arroyo, C.; Valero, V.; Currie, V.; Gilewski, T.; Theodoulou, M.; Moynahan, M. E.; Moasser, M.; Sklarin, N.; Dickler, M.; D'Andrea, G.; Cristofanilli, M.; Rivera, E.; Hortobagyi, G. N.; Norton, L.; Hudis, C. A.
Article Title: Weekly trastuzumab and paclitaxel therapy for metastatic breast cancer with analysis of efficacy by HER2 immunophenotype and gene amplification
Abstract: Purpose: This phase II study evaluated weekly trastuzumab and paclitaxel therapy in women with HER2-normal and HER2-overexpressing metastatic breast cancer. Efficacy was correlated with immunohistochemical and fluorescent in situ hybridization (FISH) assay results. Patients and Methods: Eligible patients had bidimensionally measurable metastatic breast cancer. Up to three prior chemotherapy regimens, including prior anthracycline and taxane therapy, were allowed. Trastuzumab 4 mg/kg and paclitaxel 90 mg/m2 were administered on week 1, with trastuzumab 2 mg/kg and paclitaxel 90 mg/m2 administered on subsequent weeks. HER2 status was evaluated using four different immunohistochemical assays and FISH. Results: Patients received a median of 25 weekly infusions (range, one to 85 infusions). Median delivered paclitaxel dose-intensity was 82 mg/m2/wk (range, 52 to 90 mg/m2/wk). The intent-to-treat response rate for all 95 patients enrolled was 56.8% (95% confidence interval, 47% to 67%). A response rate of 61.4% (4.5% complete response, 56.8% partial response) was observed in 88 fully assessable patients. In patients with HER2-overexpressing tumors, overall response rates ranged from 67% to 81% compared with 41% to 46% in patients with HER2-normal expression (ranges reflect the different assay methods used to assess HER2 status). Differences in response rates between patients with HER2-overexpressing tumors and those with normal HER2 expression were statistically significant for all assay methods, with CB11 and TAB250 antibodies and FISH having the strongest significance. Therapy was generally well tolerated, although three patients had serious cardiac complications. Conclusion: Weekly trastuzumab and paclitaxel therapy is active in women with metastatic breast cancer. Therapy was relatively well tolerated; however, attention to cardiac function is necessary. © 2001 by American Society of Clinical Oncology.
Keywords: adult; cancer chemotherapy; treatment outcome; aged; middle aged; major clinical study; clinical trial; drug tolerability; dose response; drug efficacy; paclitaxel; neurotoxicity; in situ hybridization, fluorescence; metastasis; phase 2 clinical trial; breast cancer; gene amplification; blood toxicity; antineoplastic combined chemotherapy protocols; drug administration schedule; breast neoplasms; antibodies, monoclonal; fluorescence in situ hybridization; immunophenotyping; trastuzumab; genes, erbb-2; heart function; oncogene neu; humans; human; female; priority journal; article
Journal Title: Journal of Clinical Oncology
Volume: 19
Issue: 10
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2001-05-15
Start Page: 2587
End Page: 2595
Language: English
PUBMED: 11352950
PROVIDER: scopus
Notes: Export Date: 21 May 2015 -- Source: Scopus