The safety of dose-dense doxorubicin and cyclophosphamide followed by paclitaxel with trastuzumab in HER-2/neu overexpressed/amplified breast cancer Journal Article


Authors: Dang, C.; Fornier, M.; Sugarman, S.; Troso-Sandoval, T.; Lake, D.; D'Andrea, G.; Seidman, A.; Sklarin, N.; Dickler, M.; Currie, V.; Gilewski, T.; Moynahan, M. E.; Drullinsky, P.; Robson, M.; Wasserheit Leiblich, C.; Mills, N.; Steingart, R.; Panageas, K.; Norton, L.; Hudis, C.
Article Title: The safety of dose-dense doxorubicin and cyclophosphamide followed by paclitaxel with trastuzumab in HER-2/neu overexpressed/amplified breast cancer
Abstract: Purpose: Dose-dense (dd) doxorubicin and cyclophosphamide (AC) followed by paclitaxel (P) is superior to every 3-weekly AC followed by P. Given the demonstrated cardiac safety for trastuzuamb (T) with conventionally scheduled AC followed by P, we tested the safety of dd AC followed by P with T. The primary end point was cardiac safety, and the secondary end points were time to recurrence and overall survival. Methods: Patients with HER-2/neu immunohistochemistry (IHC) 3+ or fluorescent in situ hybridization (FISH)-amplified breast cancer and baseline left ventricular ejection fraction (LVEF) of ≥ 55% were enrolled, regardless of tumor size or nodal status. Treatment consisted of AC (60/600 mg/m2) × 4 followed by P (175 mg/m2) × 4 every 2-weekly with pegfilgrastim (6 mg on day 2) + T ×1 year. LVEF by radionuclide scan was obtained at baseline, at months 2, 6, 9, and 18. Results: From January 2005 to November 2005, 70 patients were enrolled. The median age was 49 years (range, 27 to 72 years); median LVEF at baseline was 68% (range, 55% to 81%). At month 2 in 70 of 70 patients, the median LVEF was 67% (range, 58% to 79%); at month 6 in 67 of 70 patients, it was 66% (range, 52% to 75%); at month 9 in 68 of 70 patients, it was 65% (range, 50% to 75%); and at month 18 in 48 of 70 patients, it was 66% (range, 57% to 75%). As of December 1, 2007, the median follow-up was 28 months (range, 25 to 35 months). One patient (1%) experienced conestive heart failure (CHF). There were no cardiac deaths. Conclusion: Dose-dense AC followed by P/T followed by T is feasible and is not likely to increase the incidence of cardiac events compared to established regimens. © 2008 by American Society of Clinical Oncology.
Keywords: immunohistochemistry; adult; controlled study; human tissue; aged; middle aged; human cell; major clinical study; overall survival; clinical trial; cancer recurrence; doxorubicin; diarrhea; dose response; drug dose comparison; drug dose reduction; drug safety; paclitaxel; adjuvant therapy; chemotherapy, adjuvant; neoadjuvant therapy; drug megadose; antineoplastic agent; metabolism; in situ hybridization, fluorescence; controlled clinical trial; phase 2 clinical trial; breast cancer; gene amplification; antineoplastic combined chemotherapy protocols; epidermal growth factor receptor 2; combination chemotherapy; cyclophosphamide; deep vein thrombosis; drug effect; dose-response relationship, drug; breast neoplasms; monoclonal antibody; abdominal pain; febrile neutropenia; fever; hyperglycemia; loading drug dose; pneumonia; antibodies, monoclonal; fluorescence in situ hybridization; feasibility study; add on therapy; feasibility studies; heart failure; chemically induced disorder; adjuvant chemotherapy; breast tumor; heat shock protein 90 inhibitor; tanespimycin; colitis; receptor, erbb-2; estrogen receptor; progesterone receptor; trastuzumab; recombinant granulocyte colony stimulating factor; dyspepsia; heart left ventricle ejection fraction; heart atrium fibrillation; congestive heart failure; heart; lapatinib; pericarditis; cellulitis; heart function; sinus bradycardia; novel erythropoiesis stimulating protein; 4 [3 chloro 4 (2 pyridinylmethoxy)anilino] 3 cyano 6 (4 dimethylaminocrotonamido) 7 ethoxyquinoline; heart left ventricle function; sinusitis; diverticulitis; nail infection; ventricular dysfunction, left
Journal Title: Journal of Clinical Oncology
Volume: 26
Issue: 8
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2008-03-10
Start Page: 1216
End Page: 1222
Language: English
DOI: 10.1200/jco.2007.12.0733
PUBMED: 18323546
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 18" - "Export Date: 17 November 2011" - "CODEN: JCOND" - "Source: Scopus"
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