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

• Published in: Leukemia Vol. 18; no. 5; pp. 989 - 997
• Main Authors: HOLOWIECKI, J, GROSICKI, S, ZDZIARSKA, B, DMOSZYNSKA, A, MARIANSKA, B, PLUTA, A, ZAWILSKA, K, KOMARNICKI, M, KLOCZKO, J, SULEK, K, HAUS, O, STELLA-HOLOWIECKA, B, ROBAK, T, BARAN, W, JAKUBAS, B, PALUSZEWSKA, M, WIERZBOWSKA, A, KIELBINSKI, M, JAGODA, K, KYRCZ-KRZEMIEN, S, GIEBEL, S, HELLMANN, A, SKOTNICKI, A, JEDRZEJCZAK, W. W, KONOPKA, L, KULICZKOWSKI, K
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 01-05-2004; Nature Publishing Group
• Subjects: Acute myeloid leukemia; Adolescent; Adult; Anticancer properties; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Cladribine; Cladribine - administration & dosage; Cytarabine; Cytarabine - administration & dosage; Daunorubicin; Daunorubicin - administration & dosage; Female; Hematologic and hematopoietic diseases; Humans; Leukemia; Leukemia, Myeloid, Acute - drug therapy; Leukemia, Myeloid, Acute - mortality; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Middle Aged; Myelodysplastic syndrome; Myelodysplastic syndromes; Patients; Remission; Remission (Medicine); Survival; Toxicity; Treatment Outcome; Antineoplastic agent; Phase III trial; Hematology; Acute; Multicenter study; Malignant hemopathy; Induction treatment; Chemotherapy; Cytarabine; Daunorubicin; induction; acute myeloid leukemia; Cladribine; Remission; Acute myelocytic leukemia
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/sj.leu.2403336

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.