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Long-term results of a randomized phase 3 trial comparing idarubicin and daunorubicin in younger patients with acute myeloid leukaemia

Leukemia volume 28, pages 440–443 (2014)Cite this article

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For decades, an induction chemotherapy combining daunorubicin with cytarabine, the so-called ‘3+7’, has remained the standard of care for younger adult patients with AML.1 Neither adding other drugs to this combination nor using higher doses of cytarabine during induction has been shown to significantly improve outcome.2 However, increasing the daily dose of daunorubicin from 45 to 90 mg/m2 has been associated with higher complete remission (CR) and overall survival (OS) rates, demonstrating that anthracycline intensification could be a critical issue during the induction phase.3 In 2001, because there had been no prospective study comparing idarubicin and daunorubicin at a daily dose higher than 50 mg/m2 for 3 days in patients under the age of 60 years, the Groupe Ouest-Est des Leucémies Aigues et autres Maladies du Sang (GOELAMS) conducted a phase 3 randomized trial comparing 60 mg/m2 daunorubicin for 3 days with 8 mg/m2 idarubicin for 5 days (clinicaltrials.gov, NCT01015196).

Although the cumulative incidences of CR were not significantly different between the two arms, there were significantly more patients with at least 5% marrow blasts at d15 in the daunorubicin arm than in the idarubicin arm (Supplementary Table S2) and a second induction chemotherapy course was more frequently given to the patients of the daunorubicin arm (28% vs 21%; P=0.02). These findings likely explained why CRs were more rapidly achieved in the idarubicin arm, as depicted on the cumulative incidence curves (Supplementary Figure S1). The incidence of adverse effects during the induction phase was not different between the two groups (Supplementary Table S3).

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Acknowledgements

We thank all the GOELAMS investigators. The sponsorship was assumed by the Centre Hospitalier de Nantes, France (Projet Hospitalier de Recherche Clinique, 1998).

Author contributions

BL, AP, J-LH, NI and J-YC wrote the protocol; M-CB and PG performed data collection management, validation and statistical analyses and wrote the manuscript; CR analysed data, recruited patients, provided clinical care, performed bibliographic searches and wrote the manuscript; BL, AP, NV, JD, MH, DG, DB, NF, EJ, SL, ME-J, CB, ER, RG, MO-U, FD, J-LH, NI and JYC recruited patients and provided clinical care; IL validated cytogenetic data. All authors contributed to the gathering of the clinical or biological data and approved the report. Norbert Ifrah is the chairman of the AML scientific council of the GOELAMS.

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Authors and Affiliations

  1. Service d’Hématologie, Centre Hospitalier Universitaire de Toulouse, Centre de Recherche en Cancérologie de Toulouse, Université Paul Sabatier, Toulouse, France

    C Récher

  2. Laboratoire d’Hématologie, Centre Hospitalier Universitaire de Nantes, Nantes, France

    M C Béné

  3. Service d’Hématologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France

    B Lioure

  4. Service d’Hématologie, Centre Hospitalier Universitaire de Bordeaux, LHLCT-Inserm U1035, Université Bordeaux Segalen, Bordeaux, France

    A Pigneux

  5. Département d’Hématologie, Institut Paoli-Calmettes, Marseille, France

    N Vey

  6. Service d’Hématologie, Centre Hospitalier Universitaire de Nantes, Nantes, France

    J Delaunay

  7. Laboratoire d’Hématologie, Centre Hospitalier Universitaire de Toulouse, Toulouse, France

    I Luquet

  8. Service d’Hématologie, Centre Hospitalier Universitaire d’Angers, Angers, France

    M Hunault, N Ifrah & P Guardiola

  9. Service d’Hématologie, Centre Hospitalier Universitaire de Saint-Etienne, Saint-Etienne, France

    D Guyotat

  10. Service d’Hématologie, Assistance Publique-Hopitaux de Paris Cochin, Paris, France

    D Bouscary & F Dreyfus

  11. Service d’Hématologie, Centre Hospitalier Universitaire de Montpellier, Montpellier, France

    N Fegueux

  12. Service d’Hématologie, Centre Hospitalier Universitaire de Nîmes, Nîmes, France

    E Jourdan

  13. Service d’Hématologie, Centre Hospitalier Universitaire de Tours, Tours, France

    S Lissandre

  14. Service d’Hématologie, Centre Hospitalier Universitaire de Rennes, Rennes, France

    M Escoffre-Barbe

  15. Service d’Hématologie, Centre Hospitalier Universitaire de Nancy, Vandoeuvre les Nancy, Nancy, France

    C Bonmati

  16. Service d’Hématologie, Centre Hospitalier Universitaire de Poitiers, Poitiers, France

    E Randriamalala

  17. Service d’Hématologie, Centre Hospitalier Universitaire de Clermont-Ferrand, Université Clermont 1, EA7283, Inserm CIC-501, Clermont-Ferrand, France

    R Guièze

  18. Service d’Hématologie, Hôpital E. Muller, Mulhouse, France

    M Ojeda-Uribe

  19. Institut de Cancérologie de l’Ouest, Centre René Gauducheau, Nantes St Herblain, Nantes, France

    J L Harousseau

  20. Service d’Hématologie, Centre Hospitalier Universitaire de Grenoble, UMR 5525 CNRS, Université Joseph Fournier, Grenoble, France

    J Y Cahn

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  1. C Récher
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for the Groupe Ouest-Est d’étude des Leucémies Aiguës et autres Maladies du Sang (GOELAMS)

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Correspondence to C Récher.

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Supplementary Information accompanies this paper on the Leukemia website

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Récher, C., Béné, M., Lioure, B. et al. Long-term results of a randomized phase 3 trial comparing idarubicin and daunorubicin in younger patients with acute myeloid leukaemia. Leukemia 28, 440–443 (2014). https://doi.org/10.1038/leu.2013.290

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