PURPOSE: We reviewed data from all adjuvant NSABP breast cancer trials that tested regimens containing both doxorubicin (A) and cyclophosphamide (C) to characterize the incidence of subsequent acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). MATERIALS AND METHODS: Six complete NSABP trials have investigated AC regimens (B-15, B-16, B-18, B-22, B-23, and B-25). Six distinct AC regimens have been tested and are distinguished by differences in cyclophosphamide intensity and cumulative dose and by the presence or absence of mandated prophylactic support with growth factor and ciprofloxacin. In all regimens, A was given at 60 mg/m(2) q 21 days x 4. C was given as follows: 600 mg/m(2) q 21 days x 4 ("standard AC"); 1,200 mg(2) q 21 days x 2; 1,200 mg/m(2) q 21 days x 4; 2,400 mg/m(2) q 21 days x 2; and 2,400 mg/m(2) q 21 days x 4. Occurrence of AML/MDS was summarized by incidence per 1,000 patient-years at risk and by cumulative incidence. Rates were compared across regimens, by age, and by treatment with or without breast radiotherapy. RESULTS: The incidence of AML/MDS was sharply elevated in the more intense regimens. In patients receiving two or four cycles of C at 2,400 mg/m(2) with granulocyte colony-stimulating factor (G-CSF) support, cumulative incidence of AML/MDS at 5 years was 1.01% (95% confidence interval [CI], 0.63% to 1.62%), compared with 0.21% (95% CI, 0.11% to 0.41%) for patients treated with standard AC. Patients who received breast radiotherapy experienced more secondary AML/MDS than those who did not (RR = 2.38, P=.006), and the data indicated that G-CSF does may possibly also be independently correlated with increased risk. CONCLUSION: AC regimens employing intensified doses of cyclophosphamide requiring G-CSF support were characterized by increased rates of subsequent AML/MDS, although the incidence of AML/MDS was small relative to that of breast cancer relapse. Breast radiotherapy appeared to be associated with an increased risk of AML/MDS.
PURPOSE: We reviewed data from all adjuvant NSABP breast cancer trials that tested regimens containing both doxorubicin (A) and cyclophosphamide (C) to characterize the incidence of subsequent acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). MATERIALS AND METHODS: Six complete NSABP trials have investigated AC regimens (B-15, B-16, B-18, B-22, B-23, and B-25). Six distinct AC regimens have been tested and are distinguished by differences in cyclophosphamide intensity and cumulative dose and by the presence or absence of mandated prophylactic support with growth factor and ciprofloxacin. In all regimens, A was given at 60 mg/m(2) q 21 days x 4. C was given as follows: 600 mg/m(2) q 21 days x 4 ("standard AC"); 1,200 mg(2) q 21 days x 2; 1,200 mg/m(2) q 21 days x 4; 2,400 mg/m(2) q 21 days x 2; and 2,400 mg/m(2) q 21 days x 4. Occurrence of AML/MDS was summarized by incidence per 1,000 patient-years at risk and by cumulative incidence. Rates were compared across regimens, by age, and by treatment with or without breast radiotherapy. RESULTS: The incidence of AML/MDS was sharply elevated in the more intense regimens. In patients receiving two or four cycles of C at 2,400 mg/m(2) with granulocyte colony-stimulating factor (G-CSF) support, cumulative incidence of AML/MDS at 5 years was 1.01% (95% confidence interval [CI], 0.63% to 1.62%), compared with 0.21% (95% CI, 0.11% to 0.41%) for patients treated with standard AC. Patients who received breast radiotherapy experienced more secondary AML/MDS than those who did not (RR = 2.38, P=.006), and the data indicated that G-CSF does may possibly also be independently correlated with increased risk. CONCLUSION: AC regimens employing intensified doses of cyclophosphamide requiring G-CSF support were characterized by increased rates of subsequent AML/MDS, although the incidence of AML/MDS was small relative to that of breast cancer relapse. Breast radiotherapy appeared to be associated with an increased risk of AML/MDS.
Authors: Hilda Rachel Diamond; Maria Helena Ornellas; Alberto Orfao; Bernadete E Gomes; Mércia M Campos; Teresa S Fernandez; Roberto I da Silva; Gilda Alves; Claudia Lage; Dayse A da Silva; Arthur Moellmann-Coelho; Geydson S da Cruz; Luis Fernando Bouzas; Eliana Abdelhay Journal: J Hematol Oncol Date: 2011-09-27 Impact factor: 17.388
Authors: HeeJin Cheon; Karolina H Dziewulska; Katharine B Moosic; Kristine C Olson; Alejandro A Gru; David J Feith; Thomas P Loughran Journal: Curr Hematol Malig Rep Date: 2020-04 Impact factor: 3.952
Authors: Brian H Kushner; Kim Kramer; Shakeel Modak; Li-Xuan Qin; Karima Yataghena; Suresh C Jhanwar; Nai-Kong V Cheung Journal: Pediatr Blood Cancer Date: 2009-07 Impact factor: 3.167