Randomized studies of cytarabine dose for AML induction therapy
| Study . | Age (y) . | Patients (N) . | Experimental arm . | Control arm . | Conclusions . |
|---|---|---|---|---|---|
| SWOG10 | 15-64 | 723 | A, 2000 mg/m2/12 h d1-6* | A, 200 mg/m2 CIV d1-7 | Similar response rate |
| D, 45 mg/m2 d7-9 | D, 45 mg/m2 d5-7 | Higher early death rate | |||
| cycle 1† | cycle 1† | Longer RFS in patients aged <50 y | |||
| Similar OS | |||||
| ALSG11 | 15-60 | 301 | A, 3000 mg/m2/12 h d1/3/5/7 | A, 100 mg/m2 CIV d1-7 | Higher response rate in one course |
| D, 50 mg/m2 d5-7 | D, 50 mg/m2 d5-7 | Non significantly higher early death rate | |||
| E, 75 mg/m2 d1-7 | E, 75 mg/m2 d1-7 | Longer RFS | |||
| cycle 1‡ | cycle 1‡ | Similar OS | |||
| HOVON-SAKK12 | 18-60 | 860 | A, 1000 mg/m2/12 h d1-5 I, 12 mg/m2 d5-7 cycle 1 | A, 200 mg/m2 CIV d1-7 I, 12 mg/m2 d5-7 cycle 1 | Similar response rate |
| A, 2000 mg/m2/12 h d1/2/4/6 Am, 120 mg/m2 d3/5/7 cycle 2§ | A, 1000 mg/m2/12 h d1-6 Am, 120 mg/m2 d3/5/7 cycle 2§ | Similar EFS and OS | |||
| EORTC-GIMEMA AML1213 | 15-60 | 1942 | A, 3000 mg/m2/12 h d1/3/5/7 | A, 100 mg/m2 CIV d1-10 | Higher response rate |
| D, 50 mg/m2 d1/3/5 | D, 50 mg/m2 d1/3/5 | Similar early death rate | |||
| E, 50 mg/m2 d1-5 | E, 50 mg/m2 d1-5 | Longer RFS and OS in patients aged ≤45 y | |||
| cycle 1∥ | cycle 1∥ |
| Study . | Age (y) . | Patients (N) . | Experimental arm . | Control arm . | Conclusions . |
|---|---|---|---|---|---|
| SWOG10 | 15-64 | 723 | A, 2000 mg/m2/12 h d1-6* | A, 200 mg/m2 CIV d1-7 | Similar response rate |
| D, 45 mg/m2 d7-9 | D, 45 mg/m2 d5-7 | Higher early death rate | |||
| cycle 1† | cycle 1† | Longer RFS in patients aged <50 y | |||
| Similar OS | |||||
| ALSG11 | 15-60 | 301 | A, 3000 mg/m2/12 h d1/3/5/7 | A, 100 mg/m2 CIV d1-7 | Higher response rate in one course |
| D, 50 mg/m2 d5-7 | D, 50 mg/m2 d5-7 | Non significantly higher early death rate | |||
| E, 75 mg/m2 d1-7 | E, 75 mg/m2 d1-7 | Longer RFS | |||
| cycle 1‡ | cycle 1‡ | Similar OS | |||
| HOVON-SAKK12 | 18-60 | 860 | A, 1000 mg/m2/12 h d1-5 I, 12 mg/m2 d5-7 cycle 1 | A, 200 mg/m2 CIV d1-7 I, 12 mg/m2 d5-7 cycle 1 | Similar response rate |
| A, 2000 mg/m2/12 h d1/2/4/6 Am, 120 mg/m2 d3/5/7 cycle 2§ | A, 1000 mg/m2/12 h d1-6 Am, 120 mg/m2 d3/5/7 cycle 2§ | Similar EFS and OS | |||
| EORTC-GIMEMA AML1213 | 15-60 | 1942 | A, 3000 mg/m2/12 h d1/3/5/7 | A, 100 mg/m2 CIV d1-10 | Higher response rate |
| D, 50 mg/m2 d1/3/5 | D, 50 mg/m2 d1/3/5 | Similar early death rate | |||
| E, 50 mg/m2 d1-5 | E, 50 mg/m2 d1-5 | Longer RFS and OS in patients aged ≤45 y | |||
| cycle 1∥ | cycle 1∥ |
A, cytarabine; Am, amsacrine; CIV, continuous IV infusion; D, daunorubicin; E, etoposide; I, idarubicin; RFS, relapse-free survival; OS, overall survival.
During the first 2 years of the study, cytarabine was given at 3000 mg/m2 per bolus to patients aged <50 years, then reduced to 2000 mg/m2 per bolus because of excessive neurologic toxicity.
In both arms a second cycle, identical to the first one, was given to patients with persistent leukemia after cycle 1; all CR patients from the control arm were then randomized to either standard-dose cytarabine or HiDAC during consolidation, whereas all CR patients from the experimental arm received HiDAC during consolidation.
A second, then a third, cycle, identical to the first one, was given to patients with persistent leukemia after cycle 1 or 1-2, respectively.
After cycle 2, CR patients received either allogeneic or autologous HSCT or a third chemotherapy cycle for consolidation.
In both arms, a second cycle, identical to the first one, was given to patients with persistent leukemia after cycle 1, then all CR patients received one IDAC-containing consolidation course followed by allogeneic or autologous HSCT.