Simultaneous homoharringtonine and interferon-α in the treatment of patients with chronic-phase chronic myelogenous leukemia

Susan O'Brien, Moshe Talpaz, Jorge Cortes, Jianqin Shan, Francis J. Giles, Stefan Faderl, Deborah Thomas, Guillermo Garcia-Manero, Susie Mallard, Mary BethRios, Charles Koller, Steve Kornblau, Michael Andreeff, Anthony Murgo, Michael Keating, Hagop M. Kantarjian

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57 Scopus citations

Abstract

BACKGROUND. Homoharringtonine (HHT) has antileukemic activity in patients with Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML). Combinations of HHT, interferon-α (IFN-α), and cytarabine (ara-C) have been studied in various CML phases. The objectives of this study were to evaluate the efficacy and toxicity profiles of a combination regimen of simultaneous HHT and IFN-α therapy in patients with chronic-phase CML who were not exposed previously to either agent. METHODS. Forty-seven patients were treated: 37 patients with early chronic-phase CML (2 patients with clonal evolution) and 10 patients with late chronic-phase CML. Their median age was 62 years (range, 23-73 years). HHT was given at a dose of 2.5 mg/m 2 by continuous intravenous infusion over 24 hours daily for 5 days every month, and IFN-α was given daily at a target dose of 5 × 10 6 units/m 2 subcutaneously. Response, survival, and treatment toxicity were analyzed. RESULTS. Overall, the complete hematologic response (CHR) rate was 85%; the cytogenetic response rate was 66%, with major cytogenetic responses (Ph positive in < 35% of metaphases) in 49% of patients and complete cytogenetic responses in 21% of patients. The CHR rate, cytogenetic response rate, and major cytogenetic response rate were 84%, 69%, and 52%, respectively, in patients with early chronicphase CML. Among the 10 patients with late chronic-phase CML, the CHR rate, cytogenetic response rate, and major cytogenetic response rate were 80%, 50%, and 40%, respectively. Response rates in patients age > 60 years were 84%, 62%, and 49% for CHR, cytogenetic response, and major cytogenetic response. Myelosuppression was frequent but manageable: Anemia with hemoglobin < 8.0 g/dL occurred in 36% of patients, requiring dose adjustments and erythropoietin therapy. Nonhematologic toxicities were mainly fatigue, aches, and gastrointestinal disturbances. Dose reductions with multiple courses were significant and were due to myelosuppression: After 6-24 courses, the median daily IFN-α dose was 1 MU/m 2, and the median number of days on HHT per month was 2 days. With a median follow-up of 26 months, the estimated 2-year survival rate was 90% (95% confidence interval, 79-100%). CONCLUSIONS. The simultaneous combination of HHT and IFN-α is safe and effective, but the dose schedules that actually were delivered were significantly lower than the planned dose schedules. With the availability of signal-transductior inhibitor 571 (imatinib mesylate), studies of combination of HHT and IFN-α chemotherapy in patients with CML who have disease that fails to respond to imatinib mesylate and of combinations with imatinib mesylate need to be explored.

Original languageEnglish (US)
Pages (from-to)2024-2032
Number of pages9
JournalCancer
Volume94
Issue number7
DOIs
StatePublished - Apr 1 2002
Externally publishedYes

Keywords

  • Chronic myeloid/myelogenous leukemia
  • Chronic phase
  • Homoharringtonine
  • Interferon-α

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    O'Brien, S., Talpaz, M., Cortes, J., Shan, J., Giles, F. J., Faderl, S., Thomas, D., Garcia-Manero, G., Mallard, S., BethRios, M., Koller, C., Kornblau, S., Andreeff, M., Murgo, A., Keating, M., & Kantarjian, H. M. (2002). Simultaneous homoharringtonine and interferon-α in the treatment of patients with chronic-phase chronic myelogenous leukemia. Cancer, 94(7), 2024-2032. https://doi.org/10.1002/cncr.10436