TY - JOUR
T1 - Risk of acute myeloid leukemia and myelodysplastic syndrome in trials of adjuvant epirubicin for early breast cancer
T2 - Correlation with doses of epirubicin and cyclophosphamide
AU - Praga, Claudio
AU - Bergh, Jonas
AU - Bliss, Judith
AU - Bonneterre, Jacques
AU - Cesana, Bruno
AU - Coombes, R. Charles
AU - Fargeot, Pierre
AU - Folin, Annika
AU - Fumoleau, Pierre
AU - Giuliani, Rosa
AU - Kerbrat, Pierre
AU - Hery, Michel
AU - Nilsson, Jonas
AU - Onida, Francesco
AU - Piccart, Martine
AU - Shepherd, Lois
AU - Therasse, Patrick
AU - Wils, Jacques
AU - Rogers, David
PY - 2005
Y1 - 2005
N2 - Purpose: We reviewed follow-up of patients treated in 19 randomized trials of adjuvant epirubicin in early breast cancer to determine incidence, risk, and risk factors for subsequent acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Patients and Methods: The patients (N = 9,796) were observed from the start of adjuvant treatment (53,080 patient-years). Cases of AML or MDS (AML/MDS) were reported, with disease characteristics. Incidence and cumulative risk were compared for possible risk factors, for assigned regimens, and for administered cumulative doses of epirubicin and cyclophosphamide. Results: In 7,110 patients treated with epirubicin-containing regimens (92% of whom also received cyclophosphamide), 8-year cumulative probability of AML/MDS was 0.55% (95% CI, 0.33% to 0.78%). The risk of developing AML/MDS increased in relation to planned epirubicin dose per cycle, planned epirubicin dose-intensity, and administered cumulative doses of epirubicin and cyclophosphamide. Patients with administered cumulative doses of both epirubicin and cyclophosphamide not exceeding those used in standard regimens (≤ 720 mg/m2 and ≤ 6,300 mg/m2, respectively) had an 8-year cumulative probability of developing AML/MDS of 0.37% (95% CI, 0.13% to 0.61%) compared with 4.97% (95% CI, 2.06% to 7.87%) for patients administered higher cumulative doses of both epirubicin and cyclophosphamide. Conclusion: Patients treated with standard cumulative doses of adjuvant epirubicin (≤ 720 mg/m2) and cyclophosphamide (≤ 6,300 mg/m2) for early breast cancer have a lower probability of secondary leukemia than patients treated with higher cumulative doses. Increased risk of secondary leukemia must be considered when assessing the potential benefit to risk ratio of higher than standard doses.
AB - Purpose: We reviewed follow-up of patients treated in 19 randomized trials of adjuvant epirubicin in early breast cancer to determine incidence, risk, and risk factors for subsequent acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Patients and Methods: The patients (N = 9,796) were observed from the start of adjuvant treatment (53,080 patient-years). Cases of AML or MDS (AML/MDS) were reported, with disease characteristics. Incidence and cumulative risk were compared for possible risk factors, for assigned regimens, and for administered cumulative doses of epirubicin and cyclophosphamide. Results: In 7,110 patients treated with epirubicin-containing regimens (92% of whom also received cyclophosphamide), 8-year cumulative probability of AML/MDS was 0.55% (95% CI, 0.33% to 0.78%). The risk of developing AML/MDS increased in relation to planned epirubicin dose per cycle, planned epirubicin dose-intensity, and administered cumulative doses of epirubicin and cyclophosphamide. Patients with administered cumulative doses of both epirubicin and cyclophosphamide not exceeding those used in standard regimens (≤ 720 mg/m2 and ≤ 6,300 mg/m2, respectively) had an 8-year cumulative probability of developing AML/MDS of 0.37% (95% CI, 0.13% to 0.61%) compared with 4.97% (95% CI, 2.06% to 7.87%) for patients administered higher cumulative doses of both epirubicin and cyclophosphamide. Conclusion: Patients treated with standard cumulative doses of adjuvant epirubicin (≤ 720 mg/m2) and cyclophosphamide (≤ 6,300 mg/m2) for early breast cancer have a lower probability of secondary leukemia than patients treated with higher cumulative doses. Increased risk of secondary leukemia must be considered when assessing the potential benefit to risk ratio of higher than standard doses.
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U2 - 10.1200/JCO.2005.05.029
DO - 10.1200/JCO.2005.05.029
M3 - Article
C2 - 15961765
AN - SCOPUS:23044482675
VL - 23
SP - 4179
EP - 4191
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
SN - 0732-183X
IS - 18
ER -