Pilot study of idarubicin-based intensive-timing induction therapy for children with previously untreated acute myeloid leukemia: Children's Cancer Group Study 2941.
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.
Lange
Beverly J
BJ
Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Dinndorf
Patricia
P
Smith
Franklin O
FO
Arndt
Carola
C
Barnard
Dorothy
D
Feig
Stephen
S
Feusner
James
J
Seibel
Nita
N
Weiman
Margie
M
Aplenc
Richard
R
Gerbing
Robert
R
Alonzo
Todd A
TA
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
D000903:Antibiotics, Antineoplastic; D003561:Cytarabine; D005047:Etoposide; D003907:Dexamethasone; D013866:Thioguanine; D015255:Idarubicin; D003630:Daunorubicin