Toxicity and effectiveness of high-dose idarubicin during AML induction therapy: results of a pilot study in children.
BACKGROUND
Idarubicin (IDR) is one of the most effective, but also toxic drugs in the treatment of AML. The standard dose used in children and adults is 8-12 mg/m2 during induction.


METHODS
To improve outcome, we increased the IDR dose from 12 mg/m2 (standard dose in study AML-BFM 93), applied over three days during induction therapy (AIE = Ara-C, Idarubicin, Etoposide) to 14 mg/m2 in a pilot study including 17 patients (16 with de novo AML, one with secondary AML). Outcome and toxicities were compared with the other patients of study AML-BFM 93, treated with 3 x 12 mg/m2 IDR or 6 x 30 mg/m2 daunorubicin (DNR).


RESULTS
Patients of the pilot study achieved a good blast cell reduction in the bone marrow on day 15, a high CR rate of 94% and a low relapse rate (3/17 pts.), however, not significantly different to the IDR (12 mg/m2) group. Hematological toxicity was high, median duration until neutrophil recovery > 500/microliter was 25.0 (12-66) days, and similar to the IDR (12 mg/m2) and DNR groups. Duration of thrombocytopenia (time to > 20,000/microliter) was 21 (10-66) days in the pilot study compared to 19 (7-26) days in DNR patients (p = 0.08). Four of 17 pilot patients presented with severe WHO grades 3/4 of mucositis during induction. One patient died in long-lasting aplasia after the 3rd treatment block.


CONCLUSIONS
Results of this pilot study show that the IDR 14 mg/m2 regimen was effective but also toxic. According to our results which, however, are based on small patient numbers, an improved outcome compared to the IDR 12 mg/m2 regimen seems to be unlikely, therefore the possibly increased toxicity might not be acceptable.
Creutzig
U
U
Universitäts-Kinderkliniken in Deutschland, Münster. ucreutzig@aol.com
Körholz
D
D
Niemeyer
C M
CM
Kabisch
H
H
Graf
N
N
Reiter
A
A
Scheel-Walter
H
H
Bender-Götze
C
C
Behnisch
W
W
Hermann
J
J
Mann
G
G
Ritter
J
J
Zimmermann
M
M
D000208:Acute Disease; D000293:Adolescent; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003630:Daunorubicin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage* / Q000009:adverse effects*; D007223:Infant; D007951:Leukemia, Myeloid / Q000150:complications / Q000188:drug therapy*; D008297:Male; D010865:Pilot Projects; D012074:Remission Induction; D016896:Treatment Outcome
D000903:Antibiotics, Antineoplastic; D005047:Etoposide; D015255:Idarubicin; D003630:Daunorubicin