Intermediate-dose cytarabine plus mitoxantrone versus standard-dose cytarabine plus daunorubicin for acute myeloid leukemia in elderly patients
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/m2 twice daily on days 1, 3, 5, 7) plus mitoxantrone (10 mg/m2 days 1-3) (IMA) or standard induction therapy with cytarabine (100 mg/m2 continuously days 1-7) plus daunorubicin (45 mg/m2 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:29 |
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| Enthalten in: |
Annals of oncology : official journal of the European Society for Medical Oncology - 29(2018), 4 vom: 01. Apr., Seite 973-978 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Röllig, C [VerfasserIn] |
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| Links: |
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| Themen: |
04079A1RDZ |
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| Anmerkungen: |
Date Completed 25.11.2019 Date Revised 07.04.2020 published: Print Citation Status MEDLINE |
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| doi: |
10.1093/annonc/mdy030 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM28050019X |
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| 245 | 1 | 0 | |a Intermediate-dose cytarabine plus mitoxantrone versus standard-dose cytarabine plus daunorubicin for acute myeloid leukemia in elderly patients |
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| 500 | |a Date Completed 25.11.2019 | ||
| 500 | |a Date Revised 07.04.2020 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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) | ||
| 520 | |a Patients and methods: Patients with newly diagnosed AML >60 years were randomized to receive either intermediate-dose cytarabine (1000 mg/m2 twice daily on days 1, 3, 5, 7) plus mitoxantrone (10 mg/m2 days 1-3) (IMA) or standard induction therapy with cytarabine (100 mg/m2 continuously days 1-7) plus daunorubicin (45 mg/m2 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 | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 7 | |a Daunorubicin |2 NLM | |
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| 700 | 1 | |a Gabrecht, M |e verfasserin |4 aut | |
| 700 | 1 | |a Hänel, M |e verfasserin |4 aut | |
| 700 | 1 | |a Herbst, R |e verfasserin |4 aut | |
| 700 | 1 | |a Kaiser, U |e verfasserin |4 aut | |
| 700 | 1 | |a Schmitz, N |e verfasserin |4 aut | |
| 700 | 1 | |a Kullmer, J |e verfasserin |4 aut | |
| 700 | 1 | |a Fetscher, S |e verfasserin |4 aut | |
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| 700 | 1 | |a Mantovani-Löffler, L |e verfasserin |4 aut | |
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| 700 | 1 | |a Neuhaus, T |e verfasserin |4 aut | |
| 700 | 1 | |a Heits, F |e verfasserin |4 aut | |
| 700 | 1 | |a Einsele, H |e verfasserin |4 aut | |
| 700 | 1 | |a Ritter, B |e verfasserin |4 aut | |
| 700 | 1 | |a Bornhäuser, M |e verfasserin |4 aut | |
| 700 | 1 | |a Schetelig, J |e verfasserin |4 aut | |
| 700 | 1 | |a Thiede, C |e verfasserin |4 aut | |
| 700 | 1 | |a Mohr, B |e verfasserin |4 aut | |
| 700 | 1 | |a Schaich, M |e verfasserin |4 aut | |
| 700 | 1 | |a Platzbecker, U |e verfasserin |4 aut | |
| 700 | 1 | |a Schäfer-Eckart, K |e verfasserin |4 aut | |
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