Pilot study of idarubicin-based intensive-timing induction therapy for children with previously untreated acute myeloid leukemia

Children's Cancer Group Study 2941

Beverly J. Lange, Patricia Dinndorf, Franklin O. Smith, Carola A.S. Arndt, Dorothy Barnard, Stephen Feig, James Feusner, Nita Seibel, Margie Weiman, Richard Aplenc, Robert Gerbing, Todd A. Alonzo, Shaun Mason

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Abstract

Purpose: 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. Patients and 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% v5%; 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. Conclusion: In CCG-2941, excessive toxicity and withdrawals outweighed potential benefits of early response with IDA.

Original languageEnglish (US)
Pages (from-to)150-156
Number of pages7
JournalJournal of Clinical Oncology
Volume22
Issue number1
DOIs
StatePublished - 2004

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Idarubicin
Daunorubicin
Acute Myeloid Leukemia
Neoplasms
Therapeutics
Thioguanine
Remission Induction

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Pilot study of idarubicin-based intensive-timing induction therapy for children with previously untreated acute myeloid leukemia : Children's Cancer Group Study 2941. / Lange, Beverly J.; Dinndorf, Patricia; Smith, Franklin O.; Arndt, Carola A.S.; Barnard, Dorothy; Feig, Stephen; Feusner, James; Seibel, Nita; Weiman, Margie; Aplenc, Richard; Gerbing, Robert; Alonzo, Todd A.; Mason, Shaun.

In: Journal of Clinical Oncology, Vol. 22, No. 1, 2004, p. 150-156.

Research output: Contribution to journalArticle

Lange, BJ, Dinndorf, P, Smith, FO, Arndt, CAS, Barnard, D, Feig, S, Feusner, J, Seibel, N, Weiman, M, Aplenc, R, Gerbing, R, Alonzo, TA & Mason, S 2004, 'Pilot study of idarubicin-based intensive-timing induction therapy for children with previously untreated acute myeloid leukemia: Children's Cancer Group Study 2941', Journal of Clinical Oncology, vol. 22, no. 1, pp. 150-156. https://doi.org/10.1200/JCO.2004.04.016
Lange, Beverly J. ; Dinndorf, Patricia ; Smith, Franklin O. ; Arndt, Carola A.S. ; Barnard, Dorothy ; Feig, Stephen ; Feusner, James ; Seibel, Nita ; Weiman, Margie ; Aplenc, Richard ; Gerbing, Robert ; Alonzo, Todd A. ; Mason, Shaun. / Pilot study of idarubicin-based intensive-timing induction therapy for children with previously untreated acute myeloid leukemia : Children's Cancer Group Study 2941. In: Journal of Clinical Oncology. 2004 ; Vol. 22, No. 1. pp. 150-156.
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abstract = "Purpose: 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. Patients and 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{\%} v5{\%}; 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. Conclusion: In CCG-2941, excessive toxicity and withdrawals outweighed potential benefits of early response with IDA.",
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T1 - Pilot study of idarubicin-based intensive-timing induction therapy for children with previously untreated acute myeloid leukemia

T2 - Children's Cancer Group Study 2941

AU - Lange, Beverly J.

AU - Dinndorf, Patricia

AU - Smith, Franklin O.

AU - Arndt, Carola A.S.

AU - Barnard, Dorothy

AU - Feig, Stephen

AU - Feusner, James

AU - Seibel, Nita

AU - Weiman, Margie

AU - Aplenc, Richard

AU - Gerbing, Robert

AU - Alonzo, Todd A.

AU - Mason, Shaun

PY - 2004

Y1 - 2004

N2 - Purpose: 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. Patients and 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% v5%; 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. Conclusion: In CCG-2941, excessive toxicity and withdrawals outweighed potential benefits of early response with IDA.

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