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.
To assess the efficacy of an original DAC-7 regimen: daunorubicine (DNR) 60 mg/m2/day, days 1-3; cytarabine (AraC) 200 mg/m2/day, days 1-7; cladribine (2-CdA) 5 mg/m2/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=200) or DA-7 (without 2-CdA, n=200). The overall CR rate equaled 72% for DAC-7 and 69% for DA-7 arm (P=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=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=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=NS). There was a trend toward higher LFS rate for patients aged >40 years receiving DAC-7 compared with DA-7 regimen (44 vs 28%, P=0.05). This study proves that addition of 2-CdA increases antileukemic potency of DNR+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 >40 years.
Holowiecki
J
J
University Department of Haematology and BMT, Silesian Medical University, Katowice, Poland. holow@infomed.slam.katowice.pl
Grosicki
S
S
Robak
T
T
Kyrcz-Krzemien
S
S
Giebel
S
S
Hellmann
A
A
Skotnicki
A
A
Jedrzejczak
W W
WW
Konopka
L
L
Kuliczkowski
K
K
Zdziarska
B
B
Dmoszynska
A
A
Marianska
B
B
Pluta
A
A
Zawilska
K
K
Komarnicki
M
M
Kloczko
J
J
Sulek
K
K
Haus
O
O
Stella-Holowiecka
B
B
Baran
W
W
Jakubas
B
B
Paluszewska
M
M
Wierzbowska
A
A
Kielbinski
M
M
Jagoda
K
K
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017338:Cladribine / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D003561:Cytarabine; D017338:Cladribine; D003630:Daunorubicin