title: Azacitidine in combination with intensive induction chemotherapy in older patients with acute myeloid leukemia: The AML-AZA trial of the Study Alliance Leukemia.
abstract: DNA methylation changes are a constant feature of acute myeloid leukemia. Hypomethylating drugs such as azacitidine are active in acute myeloid leukemia (AML) as monotherapy. Azacitidine monotherapy is not curative. The AML-AZA trial tested the hypothesis that DNA methyltransferase inhibitors such as azacitidine can improve chemotherapy outcome in AML. This randomized, controlled trial compared the efficacy of azacitidine applied before each cycle of intensive chemotherapy with chemotherapy alone in older patients with untreated AML. Event-free survival (EFS) was the primary end point. In total, 214 patients with a median age of 70 years were randomized to azacitidine/chemotherapy (arm-A) or chemotherapy (arm-B). More arm-A patients (39/105; 37%) than arm-B (25/109; 23%) showed adverse cytogenetics (P=0.057). Adverse events were more frequent in arm-A (15.44) versus 13.52 in arm-B, (P=0.26), but early death rates did not differ significantly (30-day mortality: 6% versus 5%, P=0.76). Median EFS was 6 months in both arms (P=0.96). Median overall survival was 15 months for patients in arm-A compared with 21 months in arm-B (P=0.35). Azacitidine added to standard chemotherapy increases toxicity in older patients with AML, but provides no additional benefit for unselected patients.
authors.affiliation: Department of Medicine, Hematology and Oncology, University of Halle, Halle, Germany.|Department of Medicine A - Hematology, Oncology and Pneumology, University of Muenster, Muenster, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Müller-Tidow
authors.affiliation: Department of Medicine, Hematology and Oncology, University of Halle, Halle, Germany.|Department of Medicine A - Hematology, Oncology and Pneumology, University of Muenster, Muenster, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Tschanter
authors.affiliation: Department of Internal Medicine I, Dresden University Medical Center, Dresden, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Röllig
authors.affiliation: Department of Internal Medicine I, Dresden University Medical Center, Dresden, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Thiede
authors.affiliation: Department of Medicine A - Hematology, Oncology and Pneumology, University of Muenster, Muenster, Germany.|Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, RWTH Aachen University Hospital, Aachen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Koschmieder
authors.affiliation: Department of Medicine A - Hematology, Oncology and Pneumology, University of Muenster, Muenster, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Stelljes
authors.affiliation: Department of Medicine A - Hematology, Oncology and Pneumology, University of Muenster, Muenster, Germany.|Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, RWTH Aachen University Hospital, Aachen, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Koschmieder
authors.affiliation: Institute of Medical Informatics, University Hospital of Muenster, Muenster, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Dugas
authors.affiliation: Institute of Biometry, University Hospital of Muenster, Muenster, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Gerss
authors.affiliation: Center for Clinical Trials, University Hospital Muenster, Muenster, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Butterfaß-Bahloul
authors.affiliation: Center for Clinical Trials, University Hospital Muenster, Muenster, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Wagner
authors.affiliation: Institute of Biometry, University Hospital of Muenster, Muenster, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Eveslage
authors.affiliation: Department of Medical Informatics, Biometry and Epidemiology, University Bochum, Bochum, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Thiem
authors.affiliation: Department of Internal Medicine 5, University of Erlangen-Nürnberg Medical Center, Erlangen, Germany.
authors.forename: S W
authors.initials: SW
authors.lastname: Krause
authors.affiliation: Hematology and Oncology, St Bernward Hospital, Hildesheim, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Kaiser
authors.affiliation: Department of Internal Medicine II, Julius-Maximilians-Universität Würzburg, Würzburg, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Kunzmann
authors.affiliation: Department of Medicine, Hematology/Oncology, Goethe University of Frankfurt, Frankfurt, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Steffen
authors.affiliation: Department of Hematology, University of Essen Medical Center, Essen, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Noppeney
authors.affiliation: Department for Hematology/Oncology, University of Regensburg, Regensburg, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Herr
authors.affiliation: Department of Hematology and Oncology, Charité Campus Benjamin Franklin, Berlin, Germany.
authors.forename: C D
authors.initials: CD
authors.lastname: Baldus
authors.affiliation: Department of Hematology and Stem Cell Transplantation, ASKLEPIOS Klinik St. Georg, Hamburg, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Schmitz
authors.affiliation: Department of Internal Medicine III, University Hospital of Munich, Munich, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Götze
authors.affiliation: Department for Hematology/Oncology, University of Regensburg, Regensburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Reichle
authors.affiliation: Hematology and Oncology, Robert-Bosch-Krankenhaus, Stuttgart, Germany.
authors.forename: M
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authors.lastname: Kaufmann
authors.affiliation: Department Hematology, Oncology and Immunology, Philipps University Marburg, Marburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Neubauer
authors.affiliation: Department of Internal Medicine V, Klinikum Nuernberg Nord, Nuernberg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Schäfer-Eckart
authors.affiliation: Department of Internal Medicine III, Klinikum Chemnitz GmbH, Chemnitz, Germany.
authors.forename: M
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authors.lastname: Hänel
authors.affiliation: Department of Hematology and Oncology, Klinikum Osnabrück, Osnabrück, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Peceny
authors.affiliation: Department of Hematology and Oncology, HSK, Dr -Horst-Schmidt-Klinik, Wiesbaden, Germany.
authors.forename: N
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authors.lastname: Frickhofen
authors.affiliation: Department of Internal Medicine, Frankfurt (Oder) General hospital, Frankfurt/Oder, Germany.
authors.forename: M
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authors.lastname: Kiehl
authors.affiliation: Department of Oncology and Hematology, Marien Hospital Düsseldorf, Duesseldorf, Germany.
authors.forename: A
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authors.lastname: Giagounidis
authors.affiliation: Department of Hematology and Oncology, Städtische Kliniken, Bielefeld, Germany.
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authors.lastname: Görner
authors.affiliation: Department of Medicine V, Klinikum am Bruderwald, Bamberg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Repp
authors.affiliation: Department of Internal Medicine I, Westpfalz-Klinikum, Kaiserslautern, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Link
authors.affiliation: Department IV Hematology and Onkology, Klinikum Bayreuth, Bayreuth, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Kiani
authors.affiliation: Department of Internal Medicine, Stiftungsklinikum Mittelrhein, Koblenz, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Naumann
authors.affiliation: Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, RWTH Aachen University Hospital, Aachen, Germany.
authors.forename: T H
authors.initials: TH
authors.lastname: Brümmendorf
authors.affiliation: Department of Medicine, Hematology/Oncology, Goethe University of Frankfurt, Frankfurt, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Serve
authors.affiliation: Department of Internal Medicine I, Dresden University Medical Center, Dresden, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Ehninger
authors.affiliation: Department of Medicine A - Hematology, Oncology and Pneumology, University of Muenster, Muenster, Germany.
authors.forename: W E
authors.initials: WE
authors.lastname: Berdel
authors.affiliation: Department of Medicine A - Hematology, Oncology and Pneumology, University of Muenster, Muenster, Germany.|Department of Medicine, Hematology and Oncology, Klinikum Leverkusen, Leverkusen, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Krug
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001374:Azacitidine / Q000627:therapeutic use*; D003561:Cytarabine / Q000627:therapeutic use; D020732:Cytogenetic Analysis; D003630:Daunorubicin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods*; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D016019:Survival Analysis
chemical_list: D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine; D001374:Azacitidine; D003630:Daunorubicin