Dose-dense adjuvant doxorubicin and cyclophosphamide is not associated with frequent short-term changes in left ventricular ejection fraction Journal Article

Authors: Morris, P. G.; Dickler, M.; Mcarthur, H. L.; Traina, T.; Sugarman, S.; Lin, N.; Moy, B.; Come, S.; Godfrey, L.; Nulsen, B.; Chen, C.; Steingart, R.; Rugo, H.; Norton, L.; Winer, E.; Hudis, C. A.; Dang, C. T.
Article Title: Dose-dense adjuvant doxorubicin and cyclophosphamide is not associated with frequent short-term changes in left ventricular ejection fraction
Abstract: PURPOSE: Doxorubicin and cyclophosphamide (AC) every 3 weeks has been associated with frequent asymptomatic declines in left ventricular ejection fraction (LVEF). Dose-dense (dd) AC followed by paclitaxel (P) is superior to the same regimen given every third week. Herein, we report the early cardiac safety of three sequential studies of ddAC alone or with bevacizumab (B). PATIENTS AND METHODS: Patients with HER2-positive breast cancer were treated on two trials: ddAC followed by P and trastuzumab (T) and ddAC followed by PT and lapatinib. Patients with HER2-normal breast cancer were treated with B and ddAC followed by B and nanoparticle albumin-bound P. Prospective LVEF measurement by multigated radionuclide angiography scan before and after every 2 week AC for 4 cycles and at month 6 from all three trials were aggregated to determine the early risks of cardiac dysfunction. RESULTS: From January 2005 to May 2008, 245 patients were enrolled. The median age was 47 years (range, 27 to 75 years). Median LVEF pre-ddAC was 68% (range, 52% to 82%). LVEF post-ddAC was available in 241 patients (98%) and the median was unchanged at 68% (range, 47% to 81%). Per protocol no patients were ineligible for subsequent targeted biologic therapy based on LVEF decline post-ddAC. In addition, LVEF was available in 222 patients (92%) at 6 months, at which time the median LVEF was similar at 65% (range, 24% to 80%). Within 6 months of initiating chemotherapy, three patients (1.2%; 95% CI, 0.25% to 3.54%) developed CHF, all of whom received T. CONCLUSION: Dose-dense AC with or without concurrent bevacizumab is not associated with frequent acute or short-term declines in LVEF.
Keywords: adult; aged; chemotherapy, adjuvant; dose-response relationship, drug; electrophysiology; middle age; treatment outcomes; breast neoplasms -- pathology; antineoplastic agents, combined -- adverse effects; doxorubicin -- administration and dosage; paclitaxel -- administration and dosage; breast neoplasms -- drug therapy; heart diseases -- chemically induced; stroke volume -- drug effects; antibodies, monoclonal -- administration and dosage; antibodies, monoclonal -- adverse effects; antineoplastic agents, combined -- administration and dosage; cyclophosphamide -- administration and dosage; cyclophosphamide -- adverse effects; doxorubicin -- adverse effects; granulocyte colony-stimulating factor -- administration and dosage; granulocyte colony-stimulating factor -- adverse effects; paclitaxel -- adverse effects; cardiovascular system physiology -- drug effects
Journal Title: Journal of Clinical Oncology
Volume: 27
Issue: 36
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2009-12-20
Start Page: 6117
End Page: 6123
Language: English
PUBMED: 19901120
PMCID: PMC3664032
DOI: 10.1200/JCO.2008.20.2952
Notes: --- - "Accession Number: 2010512299" - "Entry Date: 20100205" - "Revision Date: 20100205" - "Publication Type: journal article" - "Journal Subset: Biomedical; Editorial Board Reviewed; Expert Peer Reviewed; Online/Print; Peer Reviewed; USA" - "Special Interest: Oncologic Care" - "NLM UID: 8309333" - "Source: cin20"
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MSK Authors
  1. Patrick Glyn Morris
    107 Morris
  2. Clifford Hudis
    840 Hudis
  3. Larry Norton
    562 Norton
  4. Chau Dang
    156 Dang
  5. Maura N Dickler
    237 Dickler
  6. Richard M Steingart
    113 Steingart
  7. Carol Chen
    25 Chen
  8. Tiffany A Traina
    153 Traina
  9. Benjamin Francis Nulsen
    8 Nulsen