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/m2 with 90 mg/m2 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/m2 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/m2, all consecutive patients received 60 mg/m2 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/m2 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/m2 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/m2 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.

2 Medizinische Klinik Universitätsklinikum Augsburg Augsburg Germany

Agendix GmbH Dresden Germany

Department of Haematology 3rd Faculty of Medicine Charles University and University Hospital Kralovske Vinohrady Hràdec Kralovè Czech Republic

Department of Hemato Oncology Palacký University Olomouc Czech Republic

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

Department of Hematology Oncology and Palliative Care Gemeinschaftsklinikum Mittelrhein Koblenz Germany

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

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

Department of Hematology Robert Bosch Krankenhaus Stuttgart Germany

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

Department of Internal Medicine 1 Hematology and Cellular Therapy University Hospital Leipzig Leipzig Germany

Department of Internal Medicine 1 University Hospital TU Dresden Dresden Germany

Department of Internal Medicine 2 University Hospital Frankfurt Frankfurt Germany

Department of Internal Medicine 3 Chemnitz Hospital Chemnitz Germany

Department of Internal Medicine 5 Nuremberg Hospital North Paracelsus Medical University Nuremberg Germany

Department of Internal Medicine 5 Universitätsklinikum Erlangen Erlangen Germany

Department of Internal Medicine 5 University of Heidelberg Heidelberg Germany

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

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

Department of Medicine A University Hospital Münster Münster Germany

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

Institute of Hematology and Blood Transfusion Prague Czech Republic

Klinik für Innere Medizin 1 Westpfalzklinikum Kaiserslautern Germany

Klinik für Innere Medizin Universitätsklinikum Jena Jena Germany

NCT Trial Center National Center of Tumor Diseases German Cancer Research Center Heidelberg Germany

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