PMID- 19776406 OWN - NLM STAT- MEDLINE DCOM- 20091002 LR - 20220321 IS - 1533-4406 (Electronic) IS - 0028-4793 (Print) IS - 0028-4793 (Linking) VI - 361 IP - 13 DP - 2009 Sep 24 TI - Anthracycline dose intensification in acute myeloid leukemia. PG - 1249-59 LID - 10.1056/NEJMoa0904544 [doi] AB - 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.) CI - 2009 Massachusetts Medical Society FAU - Fernandez, Hugo F AU - Fernandez HF AD - Department of Blood and Marrow Transplantation, Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, FL 33612, USA. hugo.fernandez@moffitt.org FAU - Sun, Zhuoxin AU - Sun Z FAU - Yao, Xiaopan AU - Yao X FAU - Litzow, Mark R AU - Litzow MR FAU - Luger, Selina M AU - Luger SM FAU - Paietta, Elisabeth M AU - Paietta EM FAU - Racevskis, Janis AU - Racevskis J FAU - Dewald, Gordon W AU - Dewald GW FAU - Ketterling, Rhett P AU - Ketterling RP FAU - Bennett, John M AU - Bennett JM FAU - Rowe, Jacob M AU - Rowe JM FAU - Lazarus, Hillard M AU - Lazarus HM FAU - Tallman, Martin S AU - Tallman MS LA - eng SI - ClinicalTrials.gov/NCT00049517 GR - CA14548/CA/NCI NIH HHS/United States GR - U10 CA013650/CA/NCI NIH HHS/United States GR - U10 CA021115/CA/NCI NIH HHS/United States GR - CA13650/CA/NCI NIH HHS/United States GR - U10 CA017145/CA/NCI NIH HHS/United States GR - U10 CA066636/CA/NCI NIH HHS/United States GR - CA17145/CA/NCI NIH HHS/United States GR - U10 CA073590/CA/NCI NIH HHS/United States GR - U10 CA015488/CA/NCI NIH HHS/United States GR - U10 CA014958/CA/NCI NIH HHS/United States GR - CA66636/CA/NCI NIH HHS/United States GR - U10 CA014548/CA/NCI NIH HHS/United States GR - U10 CA023318/CA/NCI NIH HHS/United States GR - U10 CA011083/CA/NCI NIH HHS/United States GR - CA15488/CA/NCI NIH HHS/United States GR - CA21115/CA/NCI NIH HHS/United States GR - U24 CA114737/CA/NCI NIH HHS/United States GR - CA23318/CA/NCI NIH HHS/United States PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 0 (Antibiotics, Antineoplastic) RN - 0 (KMT2A protein, human) RN - 04079A1RDZ (Cytarabine) RN - 149025-06-9 (Myeloid-Lymphoid Leukemia Protein) RN - EC 2.1.1.43 (Histone-Lysine N-Methyltransferase) RN - EC 2.7.10.1 (FLT3 protein, human) RN - EC 2.7.10.1 (fms-Like Tyrosine Kinase 3) RN - ZS7284E0ZP (Daunorubicin) SB - IM CIN - N Engl J Med. 2009 Sep 24;361(13):1301-3. PMID: 19776412 CIN - N Engl J Med. 2009 Dec 24;361(26):2578; author reply 2578. PMID: 20032330 MH - Adolescent MH - Adult MH - Age Factors MH - Antibiotics, Antineoplastic/*administration & dosage/adverse effects MH - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse effects MH - Combined Modality Therapy MH - Cytarabine/administration & dosage MH - Daunorubicin/*administration & dosage/adverse effects MH - Female MH - Histone-Lysine N-Methyltransferase MH - Humans MH - Infusions, Intravenous MH - Kaplan-Meier Estimate MH - Leukemia, Myelomonocytic, Acute/*drug therapy/genetics/mortality/therapy MH - Male MH - Middle Aged MH - Mutation MH - Myeloid-Lymphoid Leukemia Protein/genetics MH - Proportional Hazards Models MH - Remission Induction/methods MH - Risk Factors MH - Stem Cell Transplantation MH - Young Adult MH - fms-Like Tyrosine Kinase 3/genetics PMC - PMC4480917 MID - NIHMS435676 COIS- No other potential conflict of interest relevant to this article was reported. EDAT- 2009/09/25 06:00 MHDA- 2009/10/03 06:00 PMCR- 2015/06/25 CRDT- 2009/09/25 06:00 PHST- 2009/09/25 06:00 [entrez] PHST- 2009/09/25 06:00 [pubmed] PHST- 2009/10/03 06:00 [medline] PHST- 2015/06/25 00:00 [pmc-release] AID - 361/13/1249 [pii] AID - 10.1056/NEJMoa0904544 [doi] PST - ppublish SO - N Engl J Med. 2009 Sep 24;361(13):1249-59. doi: 10.1056/NEJMoa0904544.