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

Edith A. Perez, Vera J. Suman, Nancy E. Davidson, Peter A. Kaufman, Silvana Martino, Shaker R. Dakhil, James N. Ingle, Richard J. Rodeheffer, Bernard J. Gersh, Allan S. Jaffe

Research output: Contribution to journalArticle

Abstract

Purpose: 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. Patients and 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 ≤ 15% decrease in LVEF and LVEF that remained at or above the radiologic lower limit of normal (LLN); 42 patients (2.9%) had <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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)3700-3704
Number of pages5
JournalJournal of Clinical Oncology
Volume22
Issue number18
DOIs
StatePublished - 2004
Externally publishedYes

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Stroke Volume
Doxorubicin
Cyclophosphamide
Breast Neoplasms
Neoplasms
Paclitaxel
Therapeutics
Drug Therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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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. / Perez, Edith A.; Suman, Vera J.; Davidson, Nancy E.; Kaufman, Peter A.; Martino, Silvana; Dakhil, Shaker R.; Ingle, James N.; Rodeheffer, Richard J.; Gersh, Bernard J.; Jaffe, Allan S.

In: Journal of Clinical Oncology, Vol. 22, No. 18, 2004, p. 3700-3704.

Research output: Contribution to journalArticle

Perez, Edith A. ; Suman, Vera J. ; Davidson, Nancy E. ; Kaufman, Peter A. ; Martino, Silvana ; Dakhil, Shaker R. ; Ingle, James N. ; Rodeheffer, Richard J. ; Gersh, Bernard J. ; Jaffe, Allan S. / 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. In: Journal of Clinical Oncology. 2004 ; Vol. 22, No. 18. pp. 3700-3704.
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title = "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",
abstract = "Purpose: 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. Patients and 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 ≤ 15{\%} decrease in LVEF and LVEF that remained at or above the radiologic lower limit of normal (LLN); 42 patients (2.9{\%}) had <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. Conclusion: 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.",
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T1 - 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

AU - Perez, Edith A.

AU - Suman, Vera J.

AU - Davidson, Nancy E.

AU - Kaufman, Peter A.

AU - Martino, Silvana

AU - Dakhil, Shaker R.

AU - Ingle, James N.

AU - Rodeheffer, Richard J.

AU - Gersh, Bernard J.

AU - Jaffe, Allan S.

PY - 2004

Y1 - 2004

N2 - Purpose: 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. Patients and 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 ≤ 15% decrease in LVEF and LVEF that remained at or above the radiologic lower limit of normal (LLN); 42 patients (2.9%) had <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. Conclusion: 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.

AB - Purpose: 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. Patients and 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 ≤ 15% decrease in LVEF and LVEF that remained at or above the radiologic lower limit of normal (LLN); 42 patients (2.9%) had <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. Conclusion: 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.

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