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
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.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (44)
Christoph Röllig
22Department of Internal Medicine I, University Hospital TU Dresden, Dresden, Germany
Björn Steffen
26Department of Medicine II, Hematology/Oncology, Goethe University Frankfurt, University Hospital, Frankfurt, Germany
Christoph Schliemann
Jan-Henrik Mikesch
1Department of Medicine A, Hematology, Oncology, and Pneumology, University Hospital Münster, Münster, Germany
Nael Alakel
Department of Internal Medicine I, University Hospital TU Dresden, Dresden, Germany
Regina Herbst
7Department III of Internal Medicine, Klinikum Chemnitz, Chemnitz, Germany
Mathias Hänel
7Department III of Internal Medicine, Klinikum Chemnitz, Chemnitz, Germany
Richard Noppeney
11Division of Hematology/Oncology, Medizinische Klinik I, Krankenhaus der Barmherzigen Brüder, Trier, Germany
Maher Hanoun
19Department of Hematology and Stem Cell Transplantation, University Hospital Essen, Essen, Germany
Martin Kaufmann
22Department of Hematology, Oncology and Palliative Medicine, Robert Bosch Hospital, Stuttgart, Germany
Barbora Weinbergerova
7Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic
Kerstin Schäfer-Eckart
25Department of Internal Medicine 5, Oncology, Hematology and Bone Marrow Transplantation, Klinikum Nürnberg Campus Nord, Paracelsus Medical University, Nürnberg, Germany
Tim Sauer
3Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany
Andreas Neubauer
Andreas Burchert
6Universitätsklinikum Gießen und Marburg, Marburg, Germany
Claudia D. Baldus
Jolana Mertová
12Institute of Hematology and Blood Transfusion, Prague, Czech Republic
Edgar Jost
Dirk Niemann
14Department of Hematology, Oncology and Palliative Care, Gemeinschaftsklinikum Mittelrhein, Koblenz, Germany
Jan Novak
Stefan W. Krause
7Department of Internal Medicine 5, Universitätsklinikum Erlangen, Erlangen, Germany
Sebastian Scholl
Klinik für Innere Medizin, Universitätsklinikum Jena, Jena, Germany
Andreas Hochhaus
18Department of Hematology/Oncology, Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Germany
Gerhard Held
18Klinik für Innere Medizin 1, Westpfalzklinikum, Kaiserslautern, Germany
Tomas Szotkowski
19Department of Hemato-Oncology, Palacký University, Olomouc, Czech Republic
Andreas Rank
Christoph Schmid
Augsburg University Hospital
Lars Fransecky
14Department of Internal Medicine II, University Hospital Schleswig Holstein, Campus Kiel, Kiel, Germany
Sabine Kayser
Department of Internal Medicine I, Hematology and Cellular Therapy, University Hospital Leipzig, Leipzig, Germany
Markus Schaich
21Department of Hematology, Oncology and Palliative Care, Rems-Murr-Kliniken, Winnenden, Germany
Michael Krämer
Frank Fiebig
1Department of Internal Medicine I, University Hospital Dresden, Dresden, Germany
Annett Haake
1Department of Internal Medicine I, University Hospital Dresden, Dresden, Germany
Johannes Schetelig
4Department of Internal Medicine I, University Hospital Dresden, Dresden University of Technology, Dresden, Germany
Jan Moritz Middeke
Friedrich Stölzel
8Department of Internal Medicine II, Hematology and Oncology, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany
Uwe Platzbecker
Christian Thiede
7University Hospital, Dresden University of Technology, Dresden, Germany
Carsten Müller-Tidow
Wolfgang E. Berdel
Gerhard Ehninger
4Department of Internal Medicine I, University Hospital Dresden, Dresden University of Technology, Dresden, Germany
Jiri Mayer
6Department of Internal Medicine, Hematology and Oncology, University Hospital Brno and Masaryk University Brno, Brno, Czech Republic
Hubert Serve
Martin Bornhäuser