Table 4.
Randomized trials of purine analogs associated to intensive chemotherapy
| Study | Analog | Treatment phase (age range [y]) | Patients (N) | Treatment modalities | Conclusions |
|---|---|---|---|---|---|
| PALG28 | Cladribine or fludarabine | Induction (16-60) | 652 | DAC vs DAF vs DA | DAC: Higher response rate, similar RFS, longer OS* |
| cycle 1 | DAF: Similar response rate, similar RFS and OS† | ||||
| NCRI AML1629 | Clofarabine | Induction (>60) | 806 | DA vs DClo | Similar response rate‡ |
| cycle 1-2 | Similar RFS and OS | ||||
| NCRI AML1530 | Fludarabine | Induction (0-73) | 3106 | DA vs ADE vs FLAG-Ida | ADE: similar response rate, RFS and OS |
| cycle 1-2 | FLAG-Ida: Similar response rate§, higher rate of death in CR, longer RFS, similar OS | ||||
| ALFA-070231 | Clofarabine | Postremission (18-60) | 221 | CLARA vs HiDAC | Longer RFS in non allo-HSCT patients |
| consolidation cycle 1-3 | Similar OS | ||||
| CLASSIC I32 | Clofarabine | First salvage (>55) | 320 | CLARA vs IDAC | Higher response rate |
| up to 3 cycles | Higher early death rate | ||||
| Longer EFS | |||||
| Similar OS |
ADE, DA + etoposide; CLARA, clofarabine + IDAC; DA, daunorubicin + cytarabine; DAC, DA + cladribine; DAF, DA + fludarabine; DClo, daunorubicin + clofarabine; FLAG-Ida, fludarabine + IDAC + G-CSF + idarubicin; HiDAC, high-dose cytarabine; HSCT, hematopoietic stem cell transplantation; IDAC, intermediate-dose cytarabine.
*
Longer OS in patients >50 years of age, those with initial leukocyte count >50 × 109/L, and those with unfavorable cytogenetics.
†
Longer OS in patients with unfavorable cytogenetics.
‡
Lower CR in one course after DClo.
§
Higher CR in one course after FLAG-Ida.