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High-dose cytarabine in induction treatment improves the outcome of adult patients younger than age 46 years with acute myeloid leukemia: results of the EORTC-GIMEMA AML-12 trial.
- Source :
-
Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2014 Jan 20; Vol. 32 (3), pp. 219-28. Date of Electronic Publication: 2013 Dec 02. - Publication Year :
- 2014
-
Abstract
- Purpose: Cytarabine plays a pivotal role in the treatment of patients with acute myeloid leukemia (AML). Most centers use 7 to 10 days of cytarabine at a daily dose of 100 to 200 mg/m(2) for remission induction. Consensus has not been reached on the benefit of higher dosages of cytarabine.<br />Patients and Methods: The European Organisation for Research and Treatment of Cancer (EORTC) and Gruppo Italiano Malattie Ematologiche dell' Adulto (GIMEMA) Leukemia Groups conducted a randomized trial (AML-12; Combination Chemotherapy, Stem Cell Transplant and Interleukin-2 in Treating Patients With Acute Myeloid Leukemia) in 1,942 newly diagnosed patients with AML, age 15 to 60 years, comparing remission induction treatment containing daunorubicin, etoposide, and either standard-dose (SD) cytarabine (100 mg/m(2) per day by continuous infusion for 10 days) or high-dose (HD) cytarabine (3,000 mg/m(2) every 12 hours by 3-hour infusion on days 1, 3, 5, and 7). Patients in complete remission (CR) received a single consolidation cycle containing daunorubicin and intermediate-dose cytarabine (500 mg/m(2) every 12 hours for 6 days). Subsequently, a stem-cell transplantation was planned. The primary end point was survival.<br />Results: At a median follow-up of 6 years, overall survival was 38.7% for patients randomly assigned to SD cytarabine and 42.5% for those randomly assigned to HD cytarabine (log-rank test P = .06; multivariable analysis P = .009). For patients younger than age 46 years, survival was 43.3% and 51.9%, respectively (P = .009; multivariable analysis P = .003), and for patients age 46 to 60 years, survival was 33.9% and 32.9%, respectively (P = .91). CR rates were 72.0% and 78.7%, respectively (P < .001) and were 75.6% and 82.4% for patients younger than age 46 years (P = .01) and 68.3% and 74.8% for patients age 46 years and older (P = .03). Patients of all ages with very-bad-risk cytogenetic abnormalities and/or FLT3-ITD (internal tandem duplication) mutation, or with secondary AML benefitted from HD cytarabine.<br />Conclusion: HD cytarabine produces higher remission and survival rates than SD cytarabine, especially in patients younger than age 46 years.
- Subjects :
- Adolescent
Adult
Consolidation Chemotherapy
Daunorubicin administration & dosage
Drug Administration Schedule
Etoposide administration & dosage
Europe
Female
Humans
Infusions, Intravenous
Leukemia, Myeloid, Acute diagnosis
Leukemia, Myeloid, Acute genetics
Male
Middle Aged
Mutation
Risk Assessment
Risk Factors
Treatment Outcome
Antimetabolites, Antineoplastic administration & dosage
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Cytarabine administration & dosage
Induction Chemotherapy methods
Leukemia, Myeloid, Acute drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1527-7755
- Volume :
- 32
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of clinical oncology : official journal of the American Society of Clinical Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 24297940
- Full Text :
- https://doi.org/10.1200/JCO.2013.51.8571