title: Pilot study of idarubicin-based intensive-timing induction therapy for children with previously untreated acute myeloid leukemia: Children's Cancer Group Study 2941.
abstract: OBJECTIVE
  Randomized comparisons of idarubicin (IDA) with daunorubicin (DNR) show that in adults with acute myeloid leukemia (AML), IDA achieves higher remission rates and longer remission durations. In Children's Cancer Group Pilot Study CCG-2941, we assessed toxicity and feasibility of substituting 4 mg of DNR with 1 mg of IDA in intensive-timing daunorubicin-based induction therapy (DNR/DNR) used in CCG-2891.
  
  
  METHODS
  On days 1 through 3 and 10 through 14, patients received two courses of dexamethasone, cytarabine, 6-thioguanine, etoposide, and IDA (IDA/IDA). After enrollment of 65 patients, toxicity prompted replacement of IDA with DNR (IDA/DNR) on days 10 through 14 for the remaining 28 patients. Outcomes were compared with those of intensive timing in CCG-2891.
  
  
  RESULTS
  Treatment-related mortality after two courses of induction was not significantly different among the three regimens: 14% with IDA/IDA, 7% with IDA/DNR, and 9% with DNR/DNR. In course 1 of CCG-2941 IDA/IDA, 11% of patients withdrew compared with 1.5% in CCG-2891 (P <.001) and 5% in CCG-2941 IDA/DNR (P = not significant). Compared with CCG-2891 DNR/DRN, CCG-2941 IDA/IDA increased days in hospital (43 v 36 days; P =.007), mean duration of course 1 by a week (P =.002), and risk of grade 3 or 4 hyperbilirubinemia (18% v 5%; P =.02). Toxicity of IDA/DNR was not different from that of DNR/DNR in CCG-2891. The mean day 7 marrow blast percentage was 11.4% in CCG-2941 versus 21.1% in CCG-2891 (P =.004). Remission induction, survival, and event-free survival rates were not significantly different from those of CCG-2891.
  
  
  CONCLUSIONS
  In CCG-2941, excessive toxicity and withdrawals outweighed potential benefits of early response with IDA.
authors.affiliation: Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Beverly J
authors.initials: BJ
authors.lastname: Lange
authors.forename: Patricia
authors.initials: P
authors.lastname: Dinndorf
authors.forename: Franklin O
authors.initials: FO
authors.lastname: Smith
authors.forename: Carola
authors.initials: C
authors.lastname: Arndt
authors.forename: Dorothy
authors.initials: D
authors.lastname: Barnard
authors.forename: Stephen
authors.initials: S
authors.lastname: Feig
authors.forename: James
authors.initials: J
authors.lastname: Feusner
authors.forename: Nita
authors.initials: N
authors.lastname: Seibel
authors.forename: Margie
authors.initials: M
authors.lastname: Weiman
authors.forename: Richard
authors.initials: R
authors.lastname: Aplenc
authors.forename: Robert
authors.initials: R
authors.lastname: Gerbing
authors.forename: Todd A
authors.initials: TA
authors.lastname: Alonzo
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage* / Q000627:therapeutic use; D007223:Infant; D007231:Infant, Newborn; D007951:Leukemia, Myeloid / Q000188:drug therapy*; D008297:Male; D013866:Thioguanine / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D003561:Cytarabine; D005047:Etoposide; D003907:Dexamethasone; D013866:Thioguanine; D015255:Idarubicin; D003630:Daunorubicin