Idarubicin improves blast cell clearance during induction therapy in children with AML: results of study AML-BFM 93

• Published in: Leukemia Vol. 15; no. 3; pp. 348 - 354
• Main Authors: CREUTZIG, U, RITTER, J, KÜHL, J, FELDGES, A, ZIMMERMANN, M, HERMANN, J, GADNER, H, SAWATZKI, D. Blütters, NIEMEYER, C. M, SCHWABE, D, SELLE, B, BOOS, J
• Format: Conference Proceeding Journal Article
• Language: English
• Published: London Nature Publishing 01.03.2001; Nature Publishing Group
• Subjects: Antineoplastic agents; Biological and medical sciences; Bone marrow; Cardiotoxicity; Chemotherapy; Cytarabine; Daunorubicin; Etoposide; Induction therapy; Leukocytes (neutrophilic); Medical sciences; Patients; Pharmacology. Drug treatments; Recovery time; Risk groups; Survival; Toxicity; Antineoplastic agent; Toxicity; Randomization; Isomerases; Cytarabine; Daunorubicin; Complication; Clinical trial; Antimitotic; Child; Pyrimidine nucleoside; Human; DNA topoisomerase (ATP-hydrolysing); Drug combination; Enzyme; Acute; Treatment efficiency; Etoposide; Enzyme inhibitor; Malignant hemopathy; Induction treatment; Podophyllotoxine derivatives; Antibiotic; Chemotherapy; Antimetabolic; Anthracyclins; Idarubicin; Acute myelocytic leukemia
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/sj.leu.2402046

In the randomized trial AML-BFM 93 we compared 60 mg/m2/day daunorubicin with 12 mg/m2/day idarubicin for 3 days each, combined with cytarabine and etoposide during induction. Results showed a significant better blast cell reduction in the bone marrow on day 15 in patients of the idarubicin arm (25 of 144 = 17% of patients with > or = 5% blasts compared to 46 of 149 = 31% of patients after daunorubicin, Pchi2 = 0.01). This was, however, mainly seen in high risk patients treated with idarubicin (19% vs 38%, Pchi2 = 0.007). Cardiotoxicity, WHO grade 1-3 shortening fraction reduction after induction occurred in 6% patients in both arms. Bone marrow toxicity differed slightly with a median recovery time of neutrophils >500/microl of 25 days (daunorubicin) compared to 27 days (idarubicin), P = 0.05. In the total group of patients probabilities of 5 years event-free survival and disease-free survival were similar for patients treated with daunorubicin or idarubicin (49% +/- 4% vs 55% +/- 4% and 57% +/- 4% vs 64% +/- 4%, P logrank 0.29 and 0.15, respectively). However, in patients presenting with more than 5% blasts on day 15 there was a trend for a better outcome after treatment with idarubicin (P logrank 0.06). Together with the early effect seen for high risk patients these results indicate a better efficacy of idarubicin than of daunorubicin during induction with a similar rate of toxicity.