Anthracycline dose intensification in acute myeloid leukemia

Hugo F. Fernandez, Zhuoxin Sun, Xiaopan Yao, Mark R Litzow, Selina M. Luger, Elisabeth M. Paietta, Janis Racevskis, Gordon W. Dewald, Rhett P. Ketterling, John M. Bennett, Jacob M. Rowe, Hillard M. Lazarus, Martin S. Tallman

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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.)

Original languageEnglish (US)
Pages (from-to)1249-1259
Number of pages11
JournalNew England Journal of Medicine
Volume361
Issue number13
DOIs
StatePublished - Sep 24 2009

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Anthracyclines
Acute Myeloid Leukemia
Daunorubicin
Cytarabine
Survival
Young Adult
Intention to Treat Analysis
Body Surface Area
Hematopoietic Stem Cell Transplantation
Stem Cell Transplantation
Therapeutics
Intravenous Infusions
Monoclonal Antibodies
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Fernandez, H. F., Sun, Z., Yao, X., Litzow, M. R., Luger, S. M., Paietta, E. M., ... Tallman, M. S. (2009). Anthracycline dose intensification in acute myeloid leukemia. New England Journal of Medicine, 361(13), 1249-1259. https://doi.org/10.1056/NEJMoa0904544

Anthracycline dose intensification in acute myeloid leukemia. / Fernandez, Hugo F.; Sun, Zhuoxin; Yao, Xiaopan; Litzow, Mark R; Luger, Selina M.; Paietta, Elisabeth M.; Racevskis, Janis; Dewald, Gordon W.; Ketterling, Rhett P.; Bennett, John M.; Rowe, Jacob M.; Lazarus, Hillard M.; Tallman, Martin S.

In: New England Journal of Medicine, Vol. 361, No. 13, 24.09.2009, p. 1249-1259.

Research output: Contribution to journalArticle

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 2009, 'Anthracycline dose intensification in acute myeloid leukemia', New England Journal of Medicine, vol. 361, no. 13, pp. 1249-1259. https://doi.org/10.1056/NEJMoa0904544
Fernandez, Hugo F. ; Sun, Zhuoxin ; Yao, Xiaopan ; Litzow, Mark R ; Luger, Selina M. ; Paietta, Elisabeth M. ; Racevskis, Janis ; Dewald, Gordon W. ; Ketterling, Rhett P. ; Bennett, John M. ; Rowe, Jacob M. ; Lazarus, Hillard M. ; Tallman, Martin S. / Anthracycline dose intensification in acute myeloid leukemia. In: New England Journal of Medicine. 2009 ; Vol. 361, No. 13. pp. 1249-1259.
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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.)",
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AU - Fernandez, Hugo F.

AU - Sun, Zhuoxin

AU - Yao, Xiaopan

AU - Litzow, Mark R

AU - Luger, Selina M.

AU - Paietta, Elisabeth M.

AU - Racevskis, Janis

AU - Dewald, Gordon W.

AU - Ketterling, Rhett P.

AU - Bennett, John M.

AU - Rowe, Jacob M.

AU - Lazarus, Hillard M.

AU - Tallman, Martin S.

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N2 - 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.)

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.)

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