Azacitidine in combination with intensive induction chemotherapy in older patients with acute myeloid leukemia: The AML-AZA trial of the study alliance leukemia

被引：41

作者：

Mueller-Tidow, C. ^{[1
,2
]}

Tschanter, P. ^{[1
,2
]}

Roellig, C. ^{[3
]}

Thiede, C. ^{[3
]}

Koschmieder, A. ^{[2
,4
]}

Stelljes, M. ^{[2
]}

Koschmieder, S. ^{[2
,4
]}

Dugas, M. ^{[5
]}

Gerss, J. ^{[6
]}

Butterfass-Bahloul, T. ^{[7
]}

Wagner, R. ^{[7
]}

Eveslage, M. ^{[6
]}

Thiem, U. ^{[8
]}

Krause, S. W. ^{[9
]}

Kaiser, U. ^{[10
]}

Kunzmann, V. ^{[11
]}

Steffen, B. ^{[12
]}

Noppeney, R. ^{[13
]}

Herr, W. ^{[14
]}

Baldus, C. D. ^{[15
]}

Schmitz, N. ^{[16
]}

Goetze, K. ^{[17
]}

Reichle, A. ^{[14
]}

Kaufmann, M. ^{[18
]}

Neubauer, A. ^{[19
]}

Schaefer-Eckart, K. ^{[20
]}

Haenel, M. ^{[21
]}

Peceny, R. ^{[22
]}

Frickhofen, N. ^{[23
]}

Kiehl, M. ^{[24
]}

Giagounidis, A. ^{[25
]}

Goerner, M. ^{[26
]}

Repp, R. ^{[27
]}

Link, H. ^{[28
]}

Kiani, A. ^{[29
]}

Naumann, R. ^{[30
]}

Bruemmendorf, Th ^{[4
]}

Serve, H. ^{[12
]}

Ehninger, G. ^{[3
]}

Berdel, W. E. ^{[2
]}

Krug, U. ^{[2
,31
]}

机构：

[1] Univ Halle, Dept Med Hematol & Oncol, Ernst Grube Str 40, D-06120 Halle, Germany

[2] Univ Munster, Dept Med Hematol Oncol & Pneumol A, Munster, Germany

[3] Dresden Univ, Med Ctr, Dept Internal Med 1, Dresden, Germany

[4] RWTH Aachen Univ Hosp, Dept Hematol Oncol Hemostaseol & Stem Cell Transp, Aachen, Germany

[5] Univ Hosp Muenster, Inst Med Informat, Munster, Germany

[6] Univ Hosp Muenster, Inst Biometry, Munster, Germany

[7] Univ Hosp Muenster, Ctr Clin Trials, Munster, Germany

[8] Univ Bochum, Dept Med Informat Biometry & Epidemiol, Bochum, Germany

[9] Univ Erlangen Nurnberg, Med Ctr, Dept Internal Med 5, D-91054 Erlangen, Germany

[10] St Bernward Hosp, Hematol & Oncol, Hildesheim, Germany

[11] Univ Wurzburg, Dept Internal Med 2, D-97070 Wurzburg, Germany

[12] Goethe Univ Frankfurt, Dept Med Hematol Oncol, D-60054 Frankfurt, Germany

[13] Univ Essen Gesamthsch, Med Ctr, Dept Hematol, Essen, Germany

[14] Univ Regensburg, Dept Hematol Oncol, D-93053 Regensburg, Germany

[15] Charite Campus Benjamin Franklin, Dept Hematol & Oncol, Berlin, Germany

[16] ASKLEPIOS Klin St Georg, Dept Hematol & Stem Cell Transplantat, Hamburg, Germany

[17] Univ Hosp Munich, Dept Internal Med 3, Munich, Germany

[18] Robert Bosch Krankenhaus, Hematol & Oncol, Stuttgart, Germany

[19] Univ Marburg, Dept Hematol Oncol & Immunol, Marburg, Germany

[20] Klinikum Nuernberg Nord, Dept Internal Med 5, Nurnberg, Germany

[21] Klinikum Chemnitz GmbH, Dept Internal Med 3, Chemnitz, Germany

[22] Klinikum Osnabruck, Dept Hematol & Oncol, Osnabruck, Germany

[23] Dr Horst Schmidt Klin, Dept Hematol & Oncol, HSK, Wiesbaden, Germany

[24] Frankfurt Oder Gen Hosp, Dept Internal Med, Frankfurt, Germany

[25] Marien Hosp, Dept Hematol & Oncol, Dusseldorf, Germany

[26] Stadt Kliniken, Dept Hematol & Oncol, Bielefeld, Germany

[27] Klinikum Bruderwald, Dept Med 5, Bamberg, Germany

[28] Westpfalz Klinikum, Dept Internal Med 1, Kaiserslautern, Germany

[29] Klinikum Bayreuth, Dept Hematol & Onkol 4, Bayreuth, Germany

[30] Stiftungsklinikum Mittelrhein, Dept Internal Med, Koblenz, Germany

[31] Klinikum Leverkusen, Dept Med Hematol & Oncol, Leverkusen, Germany

来源：

LEUKEMIA | 2016年 / 30卷 / 03期

关键词：

CONVENTIONAL CARE REGIMENS; ELDERLY-PATIENTS; DNMT3A MUTATIONS; DNA METHYLATION; OPEN-LABEL; PHASE-III; 5-AZACYTIDINE; OUTCOMES; RECOMMENDATIONS; DECITABINE;

D O I：

10.1038/leu.2015.306

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：555 / 561

页数：7

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