Cytarabine dose for acute myeloid leukemia Full Text
New England Journal of Medicine, 03/18/2011
Clinical Article
Löwenberg B et al. – Induction therapy with cytarabine at the lower dose already produced maximal antileukemic effects for all response end points, suggesting a plateau in the dose–response relationship above this dose level. High-dose cytarabine results in excessive toxic effects without therapeutic benefit.
Methods- Compared 2 induction regimens in patients 18 to 60 years of age (median, 49) who had newly diagnosed AML
- Intermediate-dose group, totaling 431 patients, received cytarabine at dose of 200 mg per square meter given by continuous intravenous infusion for 24 hours during cycle 1 of induction therapy and 1000 mg per square meter by infusion for 3 hours twice daily during cycle 2 of induction therapy
- High-dose group, totaling 429 patients, received dose-escalated regimen of 1000 mg of cytarabine per square meter every 12 hours in cycle 1 and 2000 mg per square meter twice daily in cycle 2
- Patients with complete response did not receive additional cytarabine but received consolidation therapy in third cycle of chemotherapy (mitoxantrone–etoposide) or underwent autologous or allogeneic stem-cell transplantation
- Complete remission rates, survival rates, and toxic effects assessed for each treatment group
- At median follow-up of 5 years, no significant differences noted between intermediate-dose group and high-dose group with respect to complete remission rates (80% and 82%), probability of relapse, event-free survival at 5 years (34% and 35%), or OS (40% and 42%)
- High-dose cytarabine provided no clear advantage in any prognostic subgroup
- High-dose treatment resulted in higher incidences of grade 3 and grade 4 toxic effects (in cycle 1), prolonged hospitalization, and delayed neutrophil recovery (in cycle 2) and platelet recovery (in cycles 2 and 3)
