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Therapy

Non-infusional vs intravenous consolidation chemotherapy in elderly patients with acute myeloid leukemia: final results of the EORTC-GIMEMA AML-13 randomized phase III trial

Leukemia volume 20, pages 1723–1730 (2006)Cite this article

Abstract

In this trial, acute myeloid leukemia patients (pts) aged 61–80 years received MICE (mitoxantrone, etoposide and cytarabine) induction chemotherapy in combination with different schedules of granulocyte colony-stimulating factor administration. Pts in complete remission were subsequently randomized for two cycles of consolidation therapy: mini-ICE regimen (idarubicin, etoposide and cytarabine) given according to either an intravenous (i.v.) or a ‘non-infusional’ schedule. Among the 346 pts randomized for the second step, 331 pts received consolidation-1 and 182 consolidation-2. A total of 290 events (255 relapses, 35 deaths in first CR) have been reported. The median follow-up was 4.4 years. No significant differences were detected in terms of disease-free survival (median 9 vs 10.4 months, P=0.15, hazard ratio (HR) =1.18, 95% confidence interval (CI) 0.94–1.49) – primary end point – and survival (median 15.7 vs 17.8 months, P=0.19, HR=1.17, 95% CI 0.92–1.50). In the ‘non-infusional’ arm grade 3–4 vomiting (10 vs 2%; P=0.001) and diarrhea (10 vs 4%; P=0.03) were higher than in the ‘i.v.’ arm, whereas time to platelet recovery >20 × 109/l (median: 19 vs 23 days; P=0.02) and duration of hospitalization (mean: 15 vs 27 days; P<0.0001) was shorter. The ‘non-infusional’ consolidation regimen resulted in an antileukemic effect similar to the intravenous regimen, which was less myelosuppressive and associated with less hospitalization days.

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Acknowledgements

We acknowledge St Jude Children's Research Hospital for providing of a SAS macro allowing the computation of the cumulative incidences of relapse and of death in CR1, and their comparisons (Gray test).

We thank the Cytogeneticists of the different institutions and the members of the cytogenetic committee: A Bernheim (Institut Gustave Roussy, Villejuif), M Mancini (University La Sapienza, Rome), D Olde-Weghuis (Radboud University Nijmegen Medical Center, Nijmegen) and A Hagemeijer (UZ Gasthuisberg, Leuven). We thank the former data managers of this study: G Solbu, M Dardenne.This work was supported in part by grants from the National Cancer Institute (grant numbers 2U10-CA11488-25 through 2U10-CA11488-36). Its contents are solely the responsibility of the authors and do not represent the official views of the National Cancer Institute (Bethesda, MA, USA). This work was also supported by grants from Deutsche Krebshilfe (Germany). Pharmacia-Upjohn provided an educational grant and Zavedos free of charge. The list of EORTC-GIMEMA members who participated in this study is indicated in the appendix (‘Supplementary Information’).

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Authors and Affiliations

  1. Department of Hematology, Klinikum Grosshadern, Ludwig-Maximilians University, Munich, Germany

    U Jehn

  2. EORTC Data Center, Brussels, Belgium

    S Suciu & F Beeldens

  3. Department of Hematology, Hopital Edouard Herriot, Lyon, France

    X Thomas

  4. Department of Hematology, Hopital Necker, Paris, France

    F Lefrère

  5. Department of Hematology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

    P Muus & T de Witte

  6. Department of Hematology, Universitair Ziekenhuis Antwerpen, Edegem, Belgium

    Z Berneman

  7. Department of Hematology, Hotel-Dieu, Paris, France

    J-P Marie

  8. Department of Hematology, Ospedale Oncologico A Businco, Cagliari, Italy

    F Adamo

  9. Department of Hemato-Oncology, Centre Hospitalier Universitaire Sart-Tilman, Liège, Belgium

    G Fillet

  10. Department of Hematology, Azienda Ospedaliera Bianchi-Melacrino-Morelli, Reggio Calabria, Italy

    F Nobile

  11. Department of Hematology, Ospedale San Carlo, Potenza, Italy

    F Ricciuti

  12. Department of Hematology, Universita Del Sacro Cuore, Policlinico A Gemelli, Roma, Italy

    G Leone

  13. Department of Hematology, University degli Study Di Parma, Parma, Italy

    V Rizzoli

  14. Department of Hematology, Ospedale Di Montefiascone, Montefiascone, Italy

    M Montanaro

  15. GIMEMA Data Center, Universita Degli Studi La Sapienza, Roma, Italy

    P Fazi

  16. Fondazione GIMEMA, Universita Degli Studi La Sapienza, Roma, Italy

    F Mandelli

  17. Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands

    R Willemze

  18. Department of Hematology, Ospedale San Eugenio, Roma, Italy

    S Amadori

Authors
  1. U Jehn
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  2. S Suciu
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  3. X Thomas
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  7. J-P Marie
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  9. G Fillet
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  10. F Nobile
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  11. F Ricciuti
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  12. G Leone
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  13. V Rizzoli
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  14. M Montanaro
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  15. F Beeldens
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  16. P Fazi
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  17. F Mandelli
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  18. R Willemze
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  19. T de Witte
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  20. S Amadori
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Corresponding author

Correspondence to S Suciu.

Additional information

Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Jehn, U., Suciu, S., Thomas, X. et al. Non-infusional vs intravenous consolidation chemotherapy in elderly patients with acute myeloid leukemia: final results of the EORTC-GIMEMA AML-13 randomized phase III trial. Leukemia 20, 1723–1730 (2006). https://doi.org/10.1038/sj.leu.2404356

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