A Randomized Multicenter Study of More Intensive Versus Less Intensive Post-Remission Therapy in Elderly Patients With Acute Myelogenous Leukemia (AML) or Transformed Refractory Anemia With Excess Blasts (RAEB-t).
Patients were randomized at baseline (first R1 randomization) to receive either daunorubicin
(DNR) or idarubicin (IDA) as an anthracycline for induction and post-remission therapy. This
first randomization was stratified on centers and AML type (de novo versus post-MDS AML).
Induction chemotherapy consisted of a 4+7 course with either DNR at a daily dosage of 45
mg/m2 or IDA at a daily dosage of 9 mg/m2 for four days (day 1 to day 4) in combination with
200 mg/m2 cytarabine per day as a continuous IV infusion for seven days (day 1 to 7).
Lenograstim granulocyte colony-stimulating factor (G-CSF) was administered in all patients
from day 9 until myeloid recovery (3 consecutive days with PMN more than 1.0 G/L) by IV
infusion and at a daily dosage of 263 microg/day for a maximum of 28 days. A blood and
marrow aspiration smear examination was performed at day 21. A salvage course of
chemotherapy may be offered to patients with persistent leukemia (defined below), but only
if they did not present acquired contra-indication to further intensive chemotherapy
(baseline criteria). Salvage consisted of six 1-hour IV bolus of intermediate-dose
cytarabine (500 mg/m2/12h day 1 to 3) combined to mitoxantrone (MTZ) at a daily dosage of 12
mg/m2 for two days (day 3 and 4). G-CSF administration was stopped before salvage onset and
restarted from day 5 of the salvage course until myeloid recovery for a maximum of 28 days.
Patients reaching complete remission (CR) after induction or induction followed by salvage
were eligible for a second R2 randomization between mild versus intensive post-remission
therapy, but only if they did not present acquired contra-indication to further intensive
chemotherapy (baseline criteria). This second randomization was stratified on centers, AML
groups (de novo versus post-MDS AML), and first randomization groups. Mild post-remission
therapy was administered in out-patients and consisted of six 1+5 monthly courses with
either 45 mg/m2 DNR or 9 mg/m2 IDA for one day (day 1) in combination with 60 mg/m2/12h
cytarabine as a SC infusion for five days (day 1 to 5). No G-CSF support was given after
these six courses. Intensive post-remission therapy required another hospitalization and was
a repetition of the first 4+7 induction administered at the same doses and followed by G-CSF
administration as well.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Herve Dombret, M.D.
Acute Leukemia French Association
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)