Single or Double Induction With 7 + 3 Containing Standard or High-Dose Daunorubicin for Newly Diagnosed AML: The Randomized DaunoDouble Trial by the Study Alliance Leukemia

Journal of Clinical Oncology, vol. 43, pp. 65–74

Abstract

PURPOSE To determine the optimal daunorubicin dose and number of 7 + 3 induction cycles in newly diagnosed AML, this randomized controlled trial compared a once daily dose of 60 mg/m 2 with 90 mg/m 2 daunorubicin in the first 7 + 3 induction and one versus two cycles of 7 + 3 induction. PATIENTS AND METHODS Patients age 18-65 years with newly diagnosed AML were randomly assigned to 60 versus 90 mg/m 2 daunorubicin once daily plus cytarabine. Patients with marrow blasts below 5% on day 15 after first induction were randomly assigned to receive a second induction cycle or no second induction cycle. RESULTS Eight hundred and sixty-four patients with a median age of 52 years were randomly assigned. After a preplanned interim analysis showing no significant difference in response between 60 and 90 mg/m 2 , all consecutive patients received 60 mg/m 2 daunorubicin once daily. The proportion of good early responders was 44% versus 48% ( P = .983) with a composite complete remission (CRc) rate of 90% versus 89% after induction ( P = .691); the 3-year relapse-free survival (RFS) after 60 versus 90 mg/m 2 once daily was 54% versus 50% ( P = .561), and the 3-year overall survival (OS) was 65% versus 58% ( P = .242). Among 389 good responders, CRc rates at the end of induction were 87% after single induction and 85% after double induction. The 3-year RFS was 51% versus 60% (hazard ratio [HR], 1.3; P = .091), and the 3-year OS was 76% versus 75% after single versus double induction (HR, 1.0; P = .937). CONCLUSION The use of 90 mg/m 2 daunorubicin once daily in the context of classical 7 + 3 induction does not significantly improve early response and does not lead to higher remission rates or longer survival than 60 mg/m 2 once daily. In patients with a good early response after first induction, a second induction has only a limited impact on RFS and does not result in an OS benefit.

Authors 43

1. Christoph Röllig

   Technische Universität Dresden

   Affiliation as printed

   Department of Internal Medicine I, University Hospital TU Dresden, Dresden, Germany

2. Björn Steffen

   University Hospital Frankfurt

   Affiliation as printed

   Department of Internal Medicine II, University Hospital Frankfurt, Frankfurt, Germany

3. Christoph Schliemann

   University Hospital Münster

   Affiliation as printed

   Department of Medicine A, University Hospital Münster, Münster, Germany

4. Jan‐Henrik Mikesch

   University Hospital Münster

   Affiliation as printed

   Department of Medicine A, University Hospital Münster, Münster, Germany

5. Nael Alakel

   Technische Universität Dresden

   Affiliation as printed

   Department of Internal Medicine I, University Hospital TU Dresden, Dresden, Germany

6. Regina Herbst

   Klinikum Chemnitz

   Affiliation as printed

   Department of Internal Medicine III, Chemnitz Hospital, Chemnitz, Germany

7. Mathias Hänel

   Klinikum Chemnitz

   Affiliation as printed

   Department of Internal Medicine III, Chemnitz Hospital, Chemnitz, Germany

8. Richard Noppeney

   Essen University Hospital · University of Duisburg-Essen

   Affiliation as printed

   Department of Hematology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

9. Maher Hanoun

   Essen University Hospital · University of Duisburg-Essen

   Affiliation as printed

   Department of Hematology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

10. Martin Kaufmann

    Robert Bosch Hospital

    Affiliation as printed

    Department of Hematology, Robert-Bosch-Krankenhaus, Stuttgart, Germany

11. Barbora Weinbergerová

    University Hospital Brno

    Affiliation as printed

    Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic

12. Kerstin Schäfer‐Eckart

    Nuremberg Hospital · Paracelsus Medizinische Privatuniversität

    Affiliation as printed

    Department of Internal Medicine V, Nuremberg Hospital North, Paracelsus Medical University, Nuremberg, Germany

13. Tim Sauer

    Heidelberg University

    Affiliation as printed

    Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany

14. Andreas Neubauer

    Universitätsklinikum Gießen und Marburg

    Affiliation as printed

    Department of Internal Medicine, Hematology, Oncology and Immunology, University Hospital Marburg, Marburg, Germany

15. Andreas Burchert

    Universitätsklinikum Gießen und Marburg

    Affiliation as printed

    Department of Internal Medicine, Hematology, Oncology and Immunology, University Hospital Marburg, Marburg, Germany

16. Claudia Dorothea Baldus

    University Hospital Schleswig-Holstein

    Affiliation as printed

    Department of Hematology and Oncology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany

17. Jolana Mertová

    Institute of Haematology and Blood Transfusion

    Affiliation as printed

    Institute of Hematology and Blood Transfusion, Prague, Czech Republic

18. Edgar Jost Aachen Department of Hematology, Oncology

    RWTH Aachen University · Universitätsklinikum Aachen

    Affiliation as printed

    Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, University Hospital Aachen & CIO ABCD Aachen, RWTH Aachen, Aachen, Germany

    Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, University Hospital Aachen & CIO ABCD Aachen, RWTH Aachen, Aachen, Germany

19. Dirk Niemann

    Gemeinschaftsklinikum Mittelrhein

    Affiliation as printed

    Department of Hematology, Oncology and Palliative Care, Gemeinschaftsklinikum Mittelrhein, Koblenz, Germany

20. Stefan W. Krause

    Universitätsklinikum Erlangen

    Affiliation as printed

    Department of Internal Medicine V, Universitätsklinikum Erlangen, Erlangen, Germany

21. Sebastian Scholl

    Jena University Hospital

    Affiliation as printed

    Klinik für Innere Medizin, Universitätsklinikum Jena, Jena, Germany

22. Andreas Hochhaus

    Jena University Hospital

    Affiliation as printed

    Klinik für Innere Medizin, Universitätsklinikum Jena, Jena, Germany

23. Gerhard Held

    Westpfalz Klinikum

    Affiliation as printed

    Klinik für Innere Medizin 1, Westpfalzklinikum, Kaiserslautern, Germany

24. Tomáš Szotkowski

    Palacký University Olomouc

    Affiliation as printed

    Department of Hemato-Oncology, Palacký University, Olomouc, Czech Republic

25. Andreas Rank

    University Hospital Augsburg

    Affiliation as printed

    II. Medizinische Klinik, Universitätsklinikum Augsburg, Augsburg, Germany

26. Christoph Schmid

    University Hospital Augsburg

    Affiliation as printed

    II. Medizinische Klinik, Universitätsklinikum Augsburg, Augsburg, Germany

27. Lars R. Fransecky

    University Hospital Schleswig-Holstein

    Affiliation as printed

    Department of Hematology and Oncology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany

28. Sabine Käyser

    Heidelberg University · German Cancer Research Center · National Center for Tumor Diseases · Medizinische Fakultät Mannheim · University Hospital Leipzig · Leipzig University

    Affiliation as printed

    Department of Internal Medicine I, Hematology and Cellular Therapy, University Hospital Leipzig, Leipzig, Germany

    Insitute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany

    NCT Trial Center, National Center of Tumor Diseases, German Cancer Research Center (DKFZ), Heidelberg, Germany

29. Markus Andreas Schaich

    Rems-Murr-Klinikum

    Affiliation as printed

    Department of Hematology, Oncology and Palliative Care, Rems-Murr-Kliniken, Winnenden, Germany

30. Michael Krämer

    Technische Universität Dresden

    Affiliation as printed

    Department of Internal Medicine I, University Hospital TU Dresden, Dresden, Germany

31. Frank Fiebig

    Technische Universität Dresden

    Affiliation as printed

    Department of Internal Medicine I, University Hospital TU Dresden, Dresden, Germany

32. Annett Haake

    Technische Universität Dresden

    Affiliation as printed

    Department of Internal Medicine I, University Hospital TU Dresden, Dresden, Germany

33. Johannes Schetelig

    Technische Universität Dresden

    Affiliation as printed

    Department of Internal Medicine I, University Hospital TU Dresden, Dresden, Germany

34. Jan Moritz Middeke

    Technische Universität Dresden

    Affiliation as printed

    Department of Internal Medicine I, University Hospital TU Dresden, Dresden, Germany

35. Friedrich Stölzel

    University Hospital Schleswig-Holstein

    Affiliation as printed

    Department of Hematology and Oncology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany

36. Uwe Platzbecker

    University Hospital Leipzig · Leipzig University

    Affiliation as printed

    Department of Internal Medicine I, Hematology and Cellular Therapy, University Hospital Leipzig, Leipzig, Germany

37. Christian Thiede

    Technische Universität Dresden

    Affiliation as printed

    Agendix GmbH, Dresden, Germany

    Department of Internal Medicine I, University Hospital TU Dresden, Dresden, Germany

38. Carsten Müller‐Tidow

    Heidelberg University

    Affiliation as printed

    Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany

39. Wolfgang E. Berdel

    University Hospital Münster

    Affiliation as printed

    Department of Medicine A, University Hospital Münster, Münster, Germany

40. Gerhard Ehninger

    Technische Universität Dresden

    Affiliation as printed

    Department of Internal Medicine I, University Hospital TU Dresden, Dresden, Germany

41. Jiřı́ Mayer

    University Hospital Brno

    Affiliation as printed

    Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic

42. Hubert L. Serve

    University Hospital Frankfurt

    Affiliation as printed

    Department of Internal Medicine II, University Hospital Frankfurt, Frankfurt, Germany

43. Martin Bornhäuser

    Technische Universität Dresden

    Affiliation as printed

    Department of Internal Medicine I, University Hospital TU Dresden, Dresden, Germany