Dose-dense adjuvant Doxorubicin and cyclophosphamide is not associated with frequent short-term changes in left ventricular ejection fraction.
OBJECTIVE
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).


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.


CONCLUSIONS
Dose-dense AC with or without concurrent bevacizumab is not associated with frequent acute or short-term declines in LVEF.
Morris
Patrick G
PG
Memorial Sloan-Kettering Cancer Center, New York, NY, USA. morrisp1@mskcc.org
Dickler
Maura
M
McArthur
Heather L
HL
Traina
Tiffany
T
Sugarman
Steven
S
Lin
Nancy
N
Moy
Beverly
B
Come
Steven
S
Godfrey
Laura
L
Nulsen
Benjamin
B
Chen
Carol
C
Steingart
Richard
R
Rugo
Hope
H
Norton
Larry
L
Winer
Eric
E
Hudis
Clifford A
CA
Dang
Chau T
CT
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D054849:Cardiac Electrophysiology; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects; D006331:Heart Diseases / Q000139:chemically induced*; D006801:Humans; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D013318:Stroke Volume / Q000187:drug effects*; D000068878:Trastuzumab; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000068258:Bevacizumab; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D004317:Doxorubicin; D003520:Cyclophosphamide; D000068878:Trastuzumab; D017239:Paclitaxel; D000069585:Filgrastim