Intermediate-dose cytarabine plus mitoxantrone versus standard-dose cytarabine plus daunorubicin for acute myeloid leukemia in elderly patients

被引：28

作者：

Roellig, C. ^{[1
]}

Kramer, M. ^{[1
]}

Gabrecht, M. ^{[1
,2
]}

Haenel, M. ^{[3
]}

Herbst, R. ^{[3
]}

Kaiser, U. ^{[4
]}

Schmitz, N. ^{[5
]}

Kullmer, J. ^{[6
]}

Fetscher, S. ^{[7
]}

Link, H. ^{[8
]}

Mantoyani-Loeffler, L. ^{[9
]}

Kruempelmann, U. ^{[10
]}

Neuhaus, T. ^{[11
]}

Heits, F. ^{[12
]}

Einsele, H. ^{[13
]}

Ritter, B. ^{[14
]}

Bornhaeuser, M. ^{[1
]}

Schetelig, J. ^{[1
,15
]}

Thiede, C. ^{[1
]}

Mohr, B. ^{[1
]}

Schaich, M. ^{[16
]}

Platzbecker, U. ^{[1
]}

Schaefer-Eckart, K. ^{[17
]}

Kraemer, A. ^{[18
,19
]}

Berdel, W. E. ^{[20
]}

Serve, H. ^{[21
,22
,23
]}

Ehninger, G. ^{[1
]}

Schuler, U. S. ^{[1
]}

机构：

[1] Tech Univ Dresden, Univ Hosp, Dept Med 1, Dresden, Germany

[2] Univ Hosp Leipzig, Univ Canc Ctr Leipzig, Leipzig, Germany

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

[4] St Bernward Hosp, Dept Med 2, Hildesheim, Germany

[5] Asklepios Klin St Georg, Dept Haematol Oncol & Stem Cell Transplantat, Hamburg, Germany

[6] DIAKO, Dept Med 2, Bremen, Germany

[7] Sana Kliniken, Dept Med 3, Lubeck, Germany

[8] Westpfalzklinikum, Dept Internal Med 1, Kaiserslautern, Germany

[9] Klinikum St Georg, Dept Med Oncol & Haematol, Leipzig, Germany

[10] Klinikum Bielefeld, Dept Haematol Oncol & Palliat Care, Bielefeld, Germany

[11] St Vincenz Hosp, Dept Haemaol Med Oncol & Palliat Care, Limburg, Germany

[12] Agaples Diakonieklinikum, Dept Haematol & Oncol, Stem Cell Transplantat, Rotenburg, Germany

[13] Univ Hosp Wurzburg, Dept Med 2, Wurzburg, Germany

[14] Klinikum Kassel, Dept Haematol & Oncol, Kassel, Germany

[15] German Bone Marrow Donor Ctr, DKMS, Dresden, Germany

[16] Rems Murr Klinikum, Dept Haematol Oncol & Palliat Care, Winnenden, Germany

[17] Paracelsus Med Univ, Dept Internal Med 5, Nurnberg, Germany

[18] Heidelberg Univ, Dept Internal Med 5, Heidelberg, Germany

[19] German Canc Res Ctr, Heidelberg, Germany

[20] Univ Hosp Munster, Dept Med A, Munster, Germany

[21] Univ Hosp Frankfurt, Dept Med 2, Frankfurt, Germany

[22] German Canc Consortium, Heidelberg, Germany

[23] DKFZ, Heidelberg, Germany

来源：

ANNALS OF ONCOLOGY | 2018年 / 29卷 / 04期

关键词：

acute myeloid leukemia; cytarabine dose; elderly; REAL-WORLD; ADULTS; CHEMOTHERAPY; DIAGNOSIS; CANCER; AGE;

D O I：

10.1093/annonc/mdy030

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: The combination of intermediate-dose cytarabine plus mitoxantrone (IMA) can induce high complete remission rates with acceptable toxicity in elderly patients with acute myeloid leukemia (AML). We present the final results of a randomized-controlled trial comparing IMA with the standard 7+3 induction regimen consisting of continuous infusion cytarabine plus daunorubicin (DA). Patients and methods: Patients with newly diagnosed AML>60 years were randomized to receive either intermediate-dose cytarabine (1000 mg/m(2) twice daily on days 1, 3, 5, 7) plus mitoxantrone (10 mg/m(2) days 1-3) (IMA) or standard induction therapy with cytarabine (100 mg/m(2) continuously days 1-7) plus daunorubicin (45 mg/m(2) days 3-5) (DA). Patients in complete remission after DA received intermediate-dose cytarabine plus amsacrine as consolidation treatment, whereas patients after IMA were consolidated with standard-dose cytarabine plus mitoxantrone. Results: Between February 2005 and October 2009, 485 patients were randomized; 241 for treatment arm DA and 244 for IMA; 76% of patients were >65 years. The complete response rate after DA was 39% [95% confidence interval (95% CI): 33-45] versus 55% (95% CI: 49-61) after IMA (odds ratio 1.89, P = 0.001). The 6-week early-death rate was 14% in both arms. Relapse-free survival curves were superimposable in the first year, but separated afterwards, resulting in 3-year relapse-free survival rates of 29% versus 14% in the DA versus IMA arms, respectively (P = 0.042). The median overall survival was 10 months in both arms (P = 0.513). Conclusion: The dose escalation of cytarabine in induction therapy lead to improved remission rates in the elderly AML patients. This did not translate into a survival advantage, most likely due to differences in consolidation treatment. Thus, effective consolidation strategies need to be further explored. In combination with an effective consolidation strategy, the use of intermediate-dose cytarabine in induction may improve curative treatment for elderly AML patients.

引用

页码：973 / 978

页数：6

共 15 条

[1]

[Anonymous], 2016, BLOOD

[2] Age and acute myeloid leukemia [J].

Appelbaum, FR ;

Gundacker, H ;

Head, DR ;

Slovak, ML ;

Willman, CL ;

Godwin, JE ;

Anderson, JE ;

Petersdorf, SH .

BLOOD, 2006, 107 (09) :3481-3485

[3] Establishment of baseline toxicity expectations with standard frontline chemotherapy in acute myelogenous leukemia [J].

Atallah, Ehab ;

Cortes, Jorge ;

O'Brien, Susan ;

Pierce, Sherry ;

Rios, Mary Beth ;

Estey, Elihu ;

Markman, Maurie ;

Keating, Michael ;

Freireich, Emil J. ;

Kantarjian, Hagop .

BLOOD, 2007, 110 (10) :3547-3551

[4] Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel [J].

Doehner, Hartmut ;

Estey, Elihu ;

Grimwade, David ;

Amadori, Sergio ;

Appelbaum, Frederick R. ;

Buechner, Thomas ;

Dombret, Herve ;

Ebert, Benjamin L. ;

Fenaux, Pierre ;

Larson, Richard A. ;

Levine, Ross L. ;

Lo-Coco, Francesco ;

Naoe, Tomoki ;

Niederwieser, Dietger ;

Ossenkoppele, Gert J. ;

Sanz, Miguel ;

Sierra, Jorge ;

Tallman, Martin S. ;

Tien, Hwei-Fang ;

Wei, Andrew H. ;

Lowenberg, Bob ;

Bloomfield, Clara D. .

BLOOD, 2017, 129 (04) :424-447

[5] Equivalence Ratio for Daunorubicin to Doxorubicin in Relation to Late Heart Failure in Survivors of Childhood Cancer [J].

Feijen, Elizabeth A. M. ;

Leisenring, Wendy M. ;

Stratton, Kayla L. ;

Ness, Kirsten K. ;

van der Pal, Helena J. H. ;

Caron, Huib N. ;

Armstrong, Gregory T. ;

Green, Daniel M. ;

Hudson, Melissa M. ;

Oeffinger, Kevin C. ;

Robison, Leslie L. ;

Stovall, Marilyn ;

Kremer, Leontien C. M. ;

Chow, Eric J. .

JOURNAL OF CLINICAL ONCOLOGY, 2015, 33 (32) :3774-+

[6] Acute myeloid leukemia in the real world: why population-based registries are needed [J].

Juliusson, Gunnar ;

Lazarevic, Vladimir ;

Horstedt, Ann-Sofi ;

Hagberg, Oskar ;

Hoglund, Martin .

BLOOD, 2012, 119 (17) :3890-3899

[7] Age and acute myeloid leukemia: real world data on decision to treat and outcomes from the Swedish Acute Leukemia Registry [J].

Juliusson, Gunnar ;

Antunovic, Petar ;

Derolf, Asa ;

Lehmann, Soren ;

Mollgard, Lars ;

Stockelberg, Dick ;

Tidefelt, Ulf ;

Wahlin, Anders ;

Hoglund, Martin .

BLOOD, 2009, 113 (18) :4179-4187

[8] Long-term follow-up of the AML97 study for patients aged 60 years and above with acute myeloid leukaemia: a study of the East German Haematology and Oncology Study Group (OSHO) [J].

Kahl, C. ;

Krahl, R. ;

Becker, C. ;

Al-Ali, H. K. ;

Sayer, H. G. ;

Schulze, A. ;

Herold, M. ;

Haenel, M. ;

Scholl, S. ;

Hochhaus, A. ;

Uharek, L. ;

Maschmeyer, G. ;

Haehling, D. ;

Junghanss, C. ;

Peter, N. ;

Kaempfe, D. ;

Kettner, E. ;

Heinicke, T. ;

Fischer, T. ;

Kreibich, U. ;

Wolf, H. -H. ;

Niederwieser, D. .

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 2016, 142 (01) :305-315

[9] Increasing intensity of therapies assigned at diagnosis does not improve survival of adults with acute myeloid leukemia [J].

Krug, U. ;

Berdel, W. E. ;

Gale, R. P. ;

Haferlach, C. ;

Schnittger, S. ;

Mueller-Tidow, C. ;

Braess, J. ;

Spiekermann, K. ;

Staib, P. ;

Beelen, D. ;

Serve, H. ;

Schliemann, C. ;

Stelljes, M. ;

Balleisen, L. ;

Maschmeyer, G. ;

Grueneisen, A. ;

Eimermacher, H. ;

Giagounidis, A. ;

Rasche, H. ;

Hehlmann, R. ;

Lengfelder, E. ;

Thiel, E. ;

Reichle, A. ;

Aul, C. ;

Ludwig, W-D ;

Kern, W. ;

Haferlach, T. ;

Koepcke, W. ;

Goerlich, D. ;

Sauerland, M. C. ;

Heinecke, A. ;

Woermann, B. J. ;

Hiddemann, W. ;

Buechner, T. .

LEUKEMIA, 2016, 30 (06) :1230-1236

[10] Final results of a phase III randomized trial of CPX-351 versus 7+3 in older patients with newly diagnosed high risk (secondary) AML. [J].

Lancet, Jeffrey E. ;

Uy, Geoffrey L. ;

Cortes, Jorge E. ;

Newell, Laura F. ;

Lin, Tara L. ;

Ritchie, Ellen K. ;

Stuart, Robert K. ;

Strickland, Stephen Anthony ;

Hogge, Donna ;

Solomon, Scott R. ;

Stone, Richard M. ;

Bixby, Dale L. ;

Kolitz, Jonathan E. ;

Schiller, Gary J. ;

Wieduwilt, Matthew Joseph ;

Ryan, Daniel H. ;

Hoering, Antje ;

Chiarella, Michael ;

Louie, Arthur Chin ;

Medeiros, Bruno C. .

JOURNAL OF CLINICAL ONCOLOGY, 2016, 34 (15)

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