Randomized phase I/II study of troxacitabine combined with cytarabine, idarubicin, or topotecan in patients with refractory myeloid leukemias

Francis J. Giles, Stefan Faderl, Deborah A. Thomas, Jorge E. Cortes, Guillermo Garcia-Manero, Dan Douer, Alexandra M. Levine, Charles A. Koller, Sima S. Jeha, Susan M. O'Brien, Elihu H. Estey, Hagop M. Kantarjian

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Purpose: Troxacitabine has significant single-agent activity. This study was conducted to define the dose-limiting toxicities (DLTs) of its combination with cytarabine (ara-C), idarubicin, or topotecan. Patients and Methods: Patients with refractory acute myeloid leukemia (AML), advanced myelodysplastic syndromes (MDS), or chronic myelogenous leukemia in blastic phase (CML-BP) were initially randomly assigned to receive troxacitabine 5.0 mg/m2 by intravenous (IV) infusion over 30 minutes on days 1 to 5 with ara-C 1.0 mg/m2/d IV over 2 hours on days 1 to 5, idarubicin 12 mg/m 2 by 5 minute IV infusion on days 1 to 3, or topotecan 1.0 mg/m 2 as an continuous IV infusion on days 1 to 5. Doses were then adjusted to define DLT for each combination. Results: Eighty-seven patients (68 AML, eight MDS, 11 CML-BP) were treated. DLTs were hepatic transaminitis, hyperbilirubinemia, and hand foot syndrome (HFS) on the troxacitabine plus ara-C combination. The recommended phase II doses were 6 mg/m2 once a day for 5 days and 1.0g/m2 once a day for 5 days, respectively. DLTs were diarrhea, rash, and mucositis on the troxacitabine plus topotecan combination. The recommended phase II doses were 4 mg/m2 once a day for 5 days and 0.75 mg/m2 once a day for 5 days, respectively. DLTs were HFS, rash, and mucositis on the troxacitabine plus idarubicin combination. The recommended phase II doses were 4 mg/m2 once a day for 5 days and 9 mg/m 2 once a day for 3 days, respectively. Among 74 evaluable patients with AML or MDS, 10 (13%) achieved complete remission and four (5%) had hematologic improvement. Two of 11 (18%) evaluable patients with CML-BP returned to chronic phase. Conclusion: Troxacitabine-based combinations had significant antileukemic activity.

Original languageEnglish (US)
Pages (from-to)1050-1056
Number of pages7
JournalJournal of Clinical Oncology
Volume21
Issue number6
DOIs
StatePublished - Mar 15 2003
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Giles, F. J., Faderl, S., Thomas, D. A., Cortes, J. E., Garcia-Manero, G., Douer, D., Levine, A. M., Koller, C. A., Jeha, S. S., O'Brien, S. M., Estey, E. H., & Kantarjian, H. M. (2003). Randomized phase I/II study of troxacitabine combined with cytarabine, idarubicin, or topotecan in patients with refractory myeloid leukemias. Journal of Clinical Oncology, 21(6), 1050-1056. https://doi.org/10.1200/JCO.2003.04.023