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

共 25 条

[1] AVRAMIS VI, 1989, CANCER CHEMOTH PHARM, V24, P203
[2] Induction therapy of AML with ara-C plus daunorubicin versus ara-C plus gemtuzumab ozogamicin: a randomized phase II trial in elderly patients
Brunnberg, U.
Mohr, M.
Noppeney, R.
Duerk, H. A.
Sauerland, M. C.
Mueller-Tidow, C.
Krug, U.
Koschmieder, S.
Kessler, T.
Mesters, R. M.
Schulz, C.
Kosch, M.
Buechner, T.
Ehninger, G.
Duehrsen, U.
Serve, H.
Berdel, W. E.
[J]. ANNALS OF ONCOLOGY, 2012, 23 (04) : 990 - 996
[3] Age-Related Risk Profile and Chemotherapy Dose Response in Acute Myeloid Leukemia: A Study by the German Acute Myeloid Leukemia Cooperative Group
Buechner, Thomas
Berdel, Wolfgang E.
Haferlach, Claudia
Haferlach, Torsten
Schnittger, Susanne
Mueller-Tidow, Carsten
Braess, Jan
Spiekermann, Karsten
Kienast, Joachim
Staib, Peter
Grueneisen, Andreas
Kern, Wolfgang
Reichle, Albrecht
Maschmeyer, Georg
Aul, Carlo
Lengfelder, Eva
Sauerland, Maria-Cristina
Heinecke, Achim
Woermann, Bernhard
Hiddemann, Wolfgang
[J]. JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (01) : 61 - 69
[4] Revised recommendations of the international working group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia
Cheson, BD
Bennett, JM
Kopecky, KJ
Büchner, T
Willman, CL
Estey, EH
Schiffer, CA
Döhner, H
Tallman, MS
Lister, TA
LoCocco, F
Willemze, R
Biondi, A
Hiddemann, W
Larson, RA
Löwenberg, B
Sanz, MA
Head, DR
Ohno, R
Bloomfield, CD
[J]. JOURNAL OF CLINICAL ONCOLOGY, 2003, 21 (24) : 4642 - 4649
[5] Problems related to resistance to cytarabine in acute myeloid leukemia
Cros, E
Jordheim, L
Dumontet, C
Galmarini, CM
[J]. LEUKEMIA & LYMPHOMA, 2004, 45 (06) : 1123 - 1132
[6] Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet
Doehner, Hartmut
Estey, Elihu H.
Amadori, Sergio
Appelbaum, Frederick R.
Buechner, Thomas
Burnett, Alan K.
Dombret, Herve
Fenaux, Pierre
Grimwade, David
Larson, Richard A.
Lo-Coco, Francesco
Naoe, Tomoki
Niederwieser, Dietger
Ossenkoppele, Gert J.
Sanz, Miguel A.
Sierra, Jorge
Tallman, Martin S.
Loewenberg, Bob
Bloomfield, Clara D.
[J]. BLOOD, 2010, 115 (03) : 453 - 474
[7] Azacitidine Prolongs Overall Survival Compared With Conventional Care Regimens in Elderly Patients With Low Bone Marrow Blast Count Acute Myeloid Leukemia
Fenaux, Pierre
Mufti, Ghulam J.
Hellstrom-Lindberg, Eva
Santini, Valeria
Gattermann, Norbert
Germing, Ulrich
Sanz, Guillermo
List, Alan F.
Gore, Steven
Seymour, John F.
Dombret, Herve
Backstrom, Jay
Zimmerman, Linda
McKenzie, David
Beach, C. L.
Silverman, Lewis R.
[J]. JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (04) : 562 - 569
[8] Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study
Fenaux, Pierre
Mufti, Ghulam J.
Hellstrom-Lindberg, Eva
Santini, Valeria
Finelli, Carlo
Giagounidis, Aristoteles
Schoch, Robert
Gattermann, Norbert
Sanz, Guillermo
List, Alan
Gore, Steven D.
Seymour, John F.
Bennett, John M.
Byrd, John
Backstrom, Jay
Zimmerman, Linda
McKenzie, David
Beach, C. L.
Silverman, Lewis R.
[J]. LANCET ONCOLOGY, 2009, 10 (03) : 223 - 232
[9] Clinical impact of DNMT3A mutations in younger adult patients with acute myeloid leukemia: results of the AML Study Group (AMLSG)
Gaidzik, Verena I.
Schlenk, Richard F.
Paschka, Peter
Stoelzle, Anja
Spaeth, Daniela
Kuendgen, Andrea
von Lilienfeld-Toal, Marie
Brugger, Wolfram
Derigs, Hans Guenter
Kremers, Stephan
Greil, Richard
Raghavachar, Aruna
Ringhoffer, Mark
Salih, Helmut R.
Wattad, Mohammed
Kirchen, Heinz G.
Runde, Volker
Heil, Gerhard
Petzer, Andreas L.
Girschikofsky, Michael
Heuser, Michael
Kayser, Sabine
Goehring, Gudrun
Teleanu, Maria-Veronica
Schlegelberger, Brigitte
Ganser, Arnold
Krauter, Juergen
Bullinger, Lars
Doehner, Hartmut
Doehner, Konstanze
[J]. BLOOD, 2013, 121 (23) : 4769 - 4777
[10] Age and acute myeloid leukemia: real world data on decision to treat and outcomes from the Swedish Acute Leukemia Registry
Juliusson, Gunnar
Antunovic, Petar
Derolf, Asa
Lehmann, Soren
Mollgard, Lars
Stockelberg, Dick
Tidefelt, Ulf
Wahlin, Anders
Hoglund, Martin
[J]. BLOOD, 2009, 113 (18) : 4179 - 4187

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