Addition of cladribine to daunorubicin and cytarabine increases complete remission rate after a single course of induction treatment in acute myeloid leukemia. Multicenter, phase III study

Abstract

To assess the efficacy of an original DAC-7 regimen: daunorubicine (DNR) 60 mg/m 2 /day, days 1-3; cytarabine (AraC) 200 mg/m 2 /day, days 1-7; cladribine (2-CdA) 5 mg/m 2 /day, days 1-5, 400 untreated adult acute myeloid leukemia patients (including 63 with preceding myelodysplastic syndrome), aged 45 (16-60) years were randomized to either DAC-7 (n ¼ 200) or DA-7 (without 2-CdA, n ¼ 200). The overall CR rate equaled 72% for DAC-7 and 69% for DA-7 arm (P ¼ NS). After a single course of DAC-7 induction, the CR rate equaled 64% and was significantly higher compared to 47% in the DA-7 arm (P ¼ 0.0009). Median hospitalization time during the induction was 7 days shorter for DAC-7 compared to the DA-7 group (33 vs 40 days, P ¼ 0.002). Toxicity was comparable in both groups. The probability of 3-year leukemia-free survival (LFS) for DAC-7 and DA-7 group equaled 43 and 34%, respectively (P ¼ NS). There was a trend toward higher LFS rate for patients aged 440 years receiving DAC-7 compared with DA-7 regimen (44 vs 28%, P ¼ 0.05). This study proves that addition of 2-CdA increases antileukemic potency of DNR þ AraC regimen, thus resulting in a higher CR rate after one induction cycle when compared to DA-7, without additional toxicity. It shortens hospitalization time and may improve long-term survival in patients aged 440 years.

Homoharringtonine in combination with cytarabine and aclarubicin resulted in high complete remission rate after the first induction therapy in patients with de novo acute myeloid leukemia

“…The median duration of 12 days of nadir neutrophil count in the current cohort was shorter as compare with that of 19 days reported by other investigators. 33 Overall, compared with others, the toxicities associated with HAA regimen were more acceptable.…”

Improved treatment results for childhood acute myeloid leukemia in Taiwan

“…Complete remission rate for the standard and intensive timing arms were not significantly different, 74 and 78%, respectively. 8,53 However, induction mortality was appreciably greater with the intensively timed induction, although there were few cases of refractory leukemia. Recently, the addition of cladribine to daunorubicin and Ara-C was reported to increase the remission induction rate in adults with AML.…”

“…Recently, the addition of cladribine to daunorubicin and Ara-C was reported to increase the remission induction rate in adults with AML. 53 During postremission treatment, the effect of dose scheduling and dose intensification was demonstrated in the Children's Cancer Group 213P study. Two courses of HDAra-C and asparaginase administered at a 7-day interval resulted in superior survival rates compared with arms administered at a 28-day interval.…”

Acute myeloid leukemia—Major progress over four decades and glimpses into the future

“…In the first study, they randomized 400 patients to induction with daunorubicin and standard-dose cytarabine with or without cladribine. The addition of cladribine was associated with higher CR (64% versus 46%; p 5 0.0009) and leukemia-free survival rates (44% versus 28%; p 5 0.05) [87]. In the subsequent study, they compared 3 arms, 2 of them adding cladribine or fludarabine.…”