| Title | Anthracycline dose intensification in acute myeloid leukemia. | | Author(s) | Fernandez HF, Sun Z, Yao X, Litzow MR, Luger SM, Paietta EM, Racevskis J, Dewald GW, Ketterling RP, Bennett JM, Rowe JM, Lazarus HM, Tallman MS | | Institution | Department of Blood and Marrow Transplantation, Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, FL 33612, USA. hugo.fernandez@moffitt.org | | Source | N Engl J Med 2009 Sep 24; 361(13):1249-59. | | MeSH | Adolescent
Adult
Age Factors
Antibiotics, Antineoplastic
Antineoplastic Combined Chemotherapy Protocols
Combined Modality Therapy
Cytarabine
Daunorubicin
Female
Humans
Infusions, Intravenous
Kaplan-Meiers Estimate
Leukemia, Myelomonocytic, Acute
Male
Middle Aged
Mutation
Myeloid-Lymphoid Leukemia Protein
Proportional Hazards Models
Remission Induction
Risk Factors
Stem Cell Transplantation
Young Adult
fms-Like Tyrosine Kinase 3
| | Abstract | BACKGROUND: In young adults with acute myeloid leukemia (AML), intensification of the anthracycline dose during induction therapy has improved the rate of complete remission but not of overall survival. We evaluated the use of cytarabine plus either standard-dose or high-dose daunorubicin as induction therapy, followed by intensive consolidation therapy, in inducing complete remission to improve overall survival.
METHODS: In this phase 3 randomized trial, we assigned 657 patients between the ages of 17 and 60 years who had untreated AML to receive three once-daily doses of daunorubicin at either the standard dose (45 mg per square meter of body-surface area) or a high dose (90 mg per square meter), combined with seven daily doses of cytarabine (100 mg per square meter) by continuous intravenous infusion. Patients who had a complete remission were offered either allogeneic hematopoietic stem-cell transplantation or high-dose cytarabine, with or without a single dose of the monoclonal antibody gemtuzumab ozogamicin, followed by autologous stem-cell transplantation. The primary end point was overall survival.
RESULTS: In the intention-to-treat analysis, high-dose daunorubicin, as compared with a standard dose of the drug, resulted in a higher rate of complete remission (70.6% vs. 57.3%, P<0.001) and improved overall survival (median, 23.7 vs. 15.7 months; P=0.003). The rates of serious adverse events were similar in the two groups. Median follow-up was 25.2 months.
CONCLUSIONS: In young adults with AML, intensifying induction therapy with a high daily dose of daunorubicin improved the rate of complete remission and the duration of overall survival, as compared with the standard dose. (ClinicalTrials.gov number, NCT00049517.) | | Language | eng | | Pub Type(s) | Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
| | PubMed ID | 19776406 |
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