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

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