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Risk of Acute Leukemia Following Epirubicin-Based Adjuvant Chemotherapy: A Report From the National Cancer Institute of Canada Clinical Trials Group

From the National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario, Canada.

Address reprint requests to Michael Crump, MD, Princess Margaret Hospital, 610 University Ave, Room 5-108, Toronto, Canada M5G 2M9; email: michael.crump{at}uhn.on.ca.

Purpose: Cyclophosphamide, epirubicin, and fluorouracil (CEF), compared with classical cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy. has lead to an improvement in relapse-free and overall survival in premenopausal women with node-positive breast cancer. We undertook this analysis to more accurately define the estimate of risk of secondary acute leukemia (sAL) following epirubicin-containing chemotherapy regimens.

Patients and Methods: We assessed the conditional probability of sAL among 1,545 women who received adjuvant (n = 1,477) or neoadjuvant (n = 68) chemotherapy in four National Cancer Institute of Canada Clinical Trials Group trials from 1990 to 1999. The risks associated with epirubicin-containing regimens (CEF or epirubicin and cyclophosphamide [EC]) and other regimens (doxorubicin and cyclophosphamide [AC] or CMF) were determined.

Results: A total of 10 cases of sAL were observed (eight acute myelogeneous leukemia, two acute lymphoblastic leukemia): seven among women treated with CEF, two who had received AC, and one following CMF. Using competing risk statistics, the conditional probability of sAL was 1.7% (95% confidence interval [CI], 0.5 to 3.6) among 539 women treated with CEF chemotherapy at a follow-up of 8 years, 0.4% (95% CI, 0% to 1.3%) among the 678 who received CMF, and 1.3% (95% CI, 0% to 4.7%) among the 231 treated with AC. The conditional probability of death from breast cancer at 8 years for the entire group of women treated with epirubicin-containing regimens in all four trials was approximately 34.9%.

Conclusion: CEF chemotherapy for breast cancer carries a small increased risk of sAL compared with CMF. These estimates of acute leukemia risk are important in discussing treatment with women, especially patients with a lower risk of death from breast cancer, such as those with node-negative breast cancer.

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