Effect of doxorubicin plus cyclophosphamide on left ventricular ejection fraction in patients with breast cancer in the North Central Cancer Treatment Group N9831 Intergroup Adjuvant Trial.
OBJECTIVE
To evaluate changes in left ventricular ejection fraction (LVEF) after four cycles of adjuvant doxorubicin plus cyclophosphamide (AC) in women with human epidermal growth factor receptor 2-positive (node-positive or node-negative) breast cancer enrolled onto the North Central Cancer Treatment Group N9831 Intergroup Adjuvant Trial.


METHODS
Patients were randomly assigned to receive standard doxorubicin (60 mg/m2) plus cyclophosphamide (600 mg/m2) every 3 weeks for four cycles followed by (1) weekly paclitaxel for 12 weeks; (2) weekly paclitaxel for 12 weeks, then weekly trastuzumab for 52 weeks; or (3) weekly paclitaxel plus trastuzumab for 12 weeks, then weekly trastuzumab for 40 weeks. LVEF was monitored before and after AC.


RESULTS
Of the 1,576 eligible patients who completed AC, 1,458 had pre- and post-AC LVEF measurements taken using the same methodology (multiple-gated acquisition in 1,153 patients and echocardiogram in 305 patients). Among these 1,458 patients, 745 (51.1%) had < or = 15% decrease in LVEF and LVEF that remained at or above the radiologic lower limit of normal (LLN); 42 patients (2.9%) had < or = 15% decrease in LVEF and LVEF that decreased to or below the LLN; and 37 patients (2.5%) had an LVEF decrease of more than 15%. There was grade 2 LVEF toxicity in 96 (6.6%) of the 1,458 patients.


CONCLUSIONS
Standard AC chemotherapy is associated with frequent decreases in LVEF, which are noted when measured 3 weeks after completion of the fourth cycle. Patients are being observed to determine the long-term significance of this and the potential impact on subsequent treatment options.
Perez
Edith A
EA
North Central Cancer Treatment Group, Division of Hematology/Oncology, Mayo Clinic, Jacksonville, FL 32224, USA. perez.edith@mayo.edu
Suman
Vera J
VJ
Davidson
Nancy E
NE
Kaufman
Peter A
PA
Martino
Silvana
S
Dakhil
Shaker R
SR
Ingle
James N
JN
Rodeheffer
Richard J
RJ
Gersh
Bernard J
BJ
Jaffe
Allan S
AS
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D013318:Stroke Volume / Q000187:drug effects*; D000068878:Trastuzumab; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D004317:Doxorubicin; D003520:Cyclophosphamide; D000068878:Trastuzumab; D017239:Paclitaxel