Adaptive randomized study of idarubicin and cytarabine versus troxacitabine and cytarabine versus troxacitabine and idarubicin in untreated patients 50 years or older with adverse karyotype acute myeloid leukemia

Francis J. Giles, Hagop M. Kantarjian, Jorge E. Cortes, Guillermo Garcia-Manero, Srdan Verstovsek, Stefan Faderl, Deborah A. Thomas, Alessandra Ferrajoli, Susan O'Brien, Jay K. Wathen, Lian Chun Xiao, Donald A. Berry, Elihu H. Estey

Research output: Contribution to journalArticle

Abstract

Purpose: Troxacitabine has activity in refractory myeloid leukemia, either as a single agent or when combined with cytarabine (ara-C) or with idarubicin. A prospective, randomized study was conducted in patients aged 50 years or older with untreated, adverse karyotype, acute myeloid leukemia (AML) to assess troxacitabine-based regimes as induction therapy. Patients and Methods: Patients were randomized to receive idarubicin and ara-C (IA) versus troxacitabine and ara-C (TA) versus troxacitabine and idarubicin (TI). A Bayesian design was used to adoptively randomly assign patients to treatment. Thus, although there was initially an equal chance for randomization to IA, TA, or TI, treatment arms with a higher success rate progressively received a greater proportion of patients. Results: Thirty-four patients were treated. Randomization to TI stopped after five patients and randomization to TA stopped after 11 patients. Defining success as complete remission (CR) that occurred within 49 days of starting treatment, success rates were 55% (10 of 18 patients) with IA, 27% (three of 11 patients) with TA, and 0% (zero of five patients) with TI. Because three CRs occurred after day 49, final CR rates were 55% (10 of 18 patients) with IA, 45% (five of 11 patients) with TA, and 20% (one of five patients) with TI. The probability that TA was inferior to IA was 70%, with a 5% probability that TA would have a 20% higher CR rate than IA. Survival was equivalent with all three regimens. Conclusion: Neither troxacitabine combination was superior to IA in elderly patients with previously untreated adverse karyotype AML.

Original languageEnglish (US)
Pages (from-to)1722-1727
Number of pages6
JournalJournal of Clinical Oncology
Volume21
Issue number9
DOIs
StatePublished - May 1 2003
Externally publishedYes

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Idarubicin
Cytarabine
Karyotype
Acute Myeloid Leukemia
Random Allocation
troxacitabine
Myeloid Leukemia

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Adaptive randomized study of idarubicin and cytarabine versus troxacitabine and cytarabine versus troxacitabine and idarubicin in untreated patients 50 years or older with adverse karyotype acute myeloid leukemia. / Giles, Francis J.; Kantarjian, Hagop M.; Cortes, Jorge E.; Garcia-Manero, Guillermo; Verstovsek, Srdan; Faderl, Stefan; Thomas, Deborah A.; Ferrajoli, Alessandra; O'Brien, Susan; Wathen, Jay K.; Xiao, Lian Chun; Berry, Donald A.; Estey, Elihu H.

In: Journal of Clinical Oncology, Vol. 21, No. 9, 01.05.2003, p. 1722-1727.

Research output: Contribution to journalArticle

Giles, FJ, Kantarjian, HM, Cortes, JE, Garcia-Manero, G, Verstovsek, S, Faderl, S, Thomas, DA, Ferrajoli, A, O'Brien, S, Wathen, JK, Xiao, LC, Berry, DA & Estey, EH 2003, 'Adaptive randomized study of idarubicin and cytarabine versus troxacitabine and cytarabine versus troxacitabine and idarubicin in untreated patients 50 years or older with adverse karyotype acute myeloid leukemia', Journal of Clinical Oncology, vol. 21, no. 9, pp. 1722-1727. https://doi.org/10.1200/JCO.2003.11.016
Giles, Francis J. ; Kantarjian, Hagop M. ; Cortes, Jorge E. ; Garcia-Manero, Guillermo ; Verstovsek, Srdan ; Faderl, Stefan ; Thomas, Deborah A. ; Ferrajoli, Alessandra ; O'Brien, Susan ; Wathen, Jay K. ; Xiao, Lian Chun ; Berry, Donald A. ; Estey, Elihu H. / Adaptive randomized study of idarubicin and cytarabine versus troxacitabine and cytarabine versus troxacitabine and idarubicin in untreated patients 50 years or older with adverse karyotype acute myeloid leukemia. In: Journal of Clinical Oncology. 2003 ; Vol. 21, No. 9. pp. 1722-1727.
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abstract = "Purpose: Troxacitabine has activity in refractory myeloid leukemia, either as a single agent or when combined with cytarabine (ara-C) or with idarubicin. A prospective, randomized study was conducted in patients aged 50 years or older with untreated, adverse karyotype, acute myeloid leukemia (AML) to assess troxacitabine-based regimes as induction therapy. Patients and Methods: Patients were randomized to receive idarubicin and ara-C (IA) versus troxacitabine and ara-C (TA) versus troxacitabine and idarubicin (TI). A Bayesian design was used to adoptively randomly assign patients to treatment. Thus, although there was initially an equal chance for randomization to IA, TA, or TI, treatment arms with a higher success rate progressively received a greater proportion of patients. Results: Thirty-four patients were treated. Randomization to TI stopped after five patients and randomization to TA stopped after 11 patients. Defining success as complete remission (CR) that occurred within 49 days of starting treatment, success rates were 55{\%} (10 of 18 patients) with IA, 27{\%} (three of 11 patients) with TA, and 0{\%} (zero of five patients) with TI. Because three CRs occurred after day 49, final CR rates were 55{\%} (10 of 18 patients) with IA, 45{\%} (five of 11 patients) with TA, and 20{\%} (one of five patients) with TI. The probability that TA was inferior to IA was 70{\%}, with a 5{\%} probability that TA would have a 20{\%} higher CR rate than IA. Survival was equivalent with all three regimens. Conclusion: Neither troxacitabine combination was superior to IA in elderly patients with previously untreated adverse karyotype AML.",
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T1 - Adaptive randomized study of idarubicin and cytarabine versus troxacitabine and cytarabine versus troxacitabine and idarubicin in untreated patients 50 years or older with adverse karyotype acute myeloid leukemia

AU - Giles, Francis J.

AU - Kantarjian, Hagop M.

AU - Cortes, Jorge E.

AU - Garcia-Manero, Guillermo

AU - Verstovsek, Srdan

AU - Faderl, Stefan

AU - Thomas, Deborah A.

AU - Ferrajoli, Alessandra

AU - O'Brien, Susan

AU - Wathen, Jay K.

AU - Xiao, Lian Chun

AU - Berry, Donald A.

AU - Estey, Elihu H.

PY - 2003/5/1

Y1 - 2003/5/1

N2 - Purpose: Troxacitabine has activity in refractory myeloid leukemia, either as a single agent or when combined with cytarabine (ara-C) or with idarubicin. A prospective, randomized study was conducted in patients aged 50 years or older with untreated, adverse karyotype, acute myeloid leukemia (AML) to assess troxacitabine-based regimes as induction therapy. Patients and Methods: Patients were randomized to receive idarubicin and ara-C (IA) versus troxacitabine and ara-C (TA) versus troxacitabine and idarubicin (TI). A Bayesian design was used to adoptively randomly assign patients to treatment. Thus, although there was initially an equal chance for randomization to IA, TA, or TI, treatment arms with a higher success rate progressively received a greater proportion of patients. Results: Thirty-four patients were treated. Randomization to TI stopped after five patients and randomization to TA stopped after 11 patients. Defining success as complete remission (CR) that occurred within 49 days of starting treatment, success rates were 55% (10 of 18 patients) with IA, 27% (three of 11 patients) with TA, and 0% (zero of five patients) with TI. Because three CRs occurred after day 49, final CR rates were 55% (10 of 18 patients) with IA, 45% (five of 11 patients) with TA, and 20% (one of five patients) with TI. The probability that TA was inferior to IA was 70%, with a 5% probability that TA would have a 20% higher CR rate than IA. Survival was equivalent with all three regimens. Conclusion: Neither troxacitabine combination was superior to IA in elderly patients with previously untreated adverse karyotype AML.

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