Homoharringtonine and low-dose cytarabine in the management of late chronic-phase chronic myelogenous leukemia

Hagop M. Kantarjian, Moshe Talpaz, Terry L. Smith, Jorge Cortes, Francis J. Giles, Mary Beth Rios, Susie Mallard, James Gajewski, Anthony Murgo, Bruce Cheson, Susan O'Brien

Research output: Contribution to journalArticle

75 Scopus citations

Abstract

Purpose: To evaluate the efficacy and toxicity profiles of a combination regimen of homoharringtonine (HHT) and low-dose cytarabine (ara-C) in patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) who had experienced treatment failure with interferon alfa (IFNα) therapy. Patients and Methods: One hundred five patients were treated: 100 in chronic phase (15 with cytogenetic clonal evolution) and five in accelerated phase. Their median age was 52 years; all had been treated unsuccessfully with IFNα; 94% were in late chronic phase; 43% had been exposed to ara-C and 11% had been exposed to HHT. Patients received HHT 2.5 mg/m2 by continuous infusion daily for 5 days and ara-C 15 mg/m2 daily in two subcutaneous injections for 5 days every 4 weeks. The outcome of the 100 patients in chronic phase was compared with a previous study group of 73 patients treated with HHT alone. Results: Overall, the complete hematologic response (CHR) rate in chronic phase was 72%; the cytogenetic response rate was 32% (major response, 15%; complete response, 5%). Toxicities were acceptable, mostly related to moderate diarrhea (3%), headaches (3%), cardiovascular events (3%), and myelosuppression-associated complications (3% to 14%). With a median follow-up period of 25 months, the estimated 4-year survival rate was 55%. Response rates were identical with HHT plus ara-C versus HHT alone, but the survival was significantly longer with the combination after accounting for differences in the study groups and by multivariate analysis. Conclusion: The combination regimen of HHT and ara-C is effective and safe in patients with CML who have experienced treatment failure with IFNα and needs to be investigated together with IFNα as part of front-line CML therapy. The addition of ara-C did not improve the response rates but may have improved survival, perhaps through suppression of clones related to disease transformation. (C) 2000 by American Society of Clinical Oncology.

Original languageEnglish (US)
Pages (from-to)3513-3521
Number of pages9
JournalJournal of Clinical Oncology
Volume18
Issue number20
DOIs
StatePublished - Oct 15 2000
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Kantarjian, H. M., Talpaz, M., Smith, T. L., Cortes, J., Giles, F. J., Rios, M. B., Mallard, S., Gajewski, J., Murgo, A., Cheson, B., & O'Brien, S. (2000). Homoharringtonine and low-dose cytarabine in the management of late chronic-phase chronic myelogenous leukemia. Journal of Clinical Oncology, 18(20), 3513-3521. https://doi.org/10.1200/JCO.2000.18.20.3513