title: Toxicity and effectiveness of high-dose idarubicin during AML induction therapy: results of a pilot study in children.
abstract: 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.
authors.affiliation: Universitäts-Kinderkliniken in Deutschland, Münster. ucreutzig@aol.com
authors.forename: U
authors.initials: U
authors.lastname: Creutzig
authors.forename: D
authors.initials: D
authors.lastname: Körholz
authors.forename: C M
authors.initials: CM
authors.lastname: Niemeyer
authors.forename: H
authors.initials: H
authors.lastname: Kabisch
authors.forename: N
authors.initials: N
authors.lastname: Graf
authors.forename: A
authors.initials: A
authors.lastname: Reiter
authors.forename: H
authors.initials: H
authors.lastname: Scheel-Walter
authors.forename: C
authors.initials: C
authors.lastname: Bender-Götze
authors.forename: W
authors.initials: W
authors.lastname: Behnisch
authors.forename: J
authors.initials: J
authors.lastname: Hermann
authors.forename: G
authors.initials: G
authors.lastname: Mann
authors.forename: J
authors.initials: J
authors.lastname: Ritter
authors.forename: M
authors.initials: M
authors.lastname: Zimmermann
mesh_terms: 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
chemical_list: D000903:Antibiotics, Antineoplastic; D005047:Etoposide; D015255:Idarubicin; D003630:Daunorubicin