Treatment of Philadelphia chromosome-positive chronic myelogenous leukemia with weekly polyethylene glycol formulation of interferon-alpha-2b and low-dose cytosine arabinoside

Guillermo Garcia-Manero, Moshe Talpaz, Francis J. Giles, Jorge Cortes, Stefan Faderl, Susan O'Brien, Deborah Thomas, Srdan Verstovsek, Mary Beth Rios, Jianquin Shan, Alessandra Ferrajoli, William Wierda, Hagop M. Kantarjian

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

BACKGROUND. To evaluate the activity and toxicity of weekly Schering 54301, a polyethylene glycol formulation of interferon-α-2b (PEG-IFN-α-2b), with cytosine arabinoside (ara-C) in patients with chronic myelogenous leukemia (CML). METHODS. Seventy-six patients with Philadelphia chromosome (Ph)-positive early chronic-phase CML were treated with the combination of PEG-IFN-α-2b and ara-C (10 mg daily subcutaneously [s.c.]). The starting dose of PEG-IFN-α-2b was 6 μg/kg s.c. weekly in the first 24 patients but was reduced to 4.5 μg/kg in the next 52 patients. RESULTS. Overall, 73% of patients had a complete hematologic response, 35% of patients had a major cytogenetic response (Ph < 35%), and 21% of patients had a complete cytogenetic response (Ph = 0%). With a median follow-up of 19 months, the estimated 2-year survival rate was 89%. Therapy was discontinued in 24% of patients due to Grade III-IV toxicity. Frequent severe side effects that required dose reductions included neutropenia (49%), fatigue (43%), and neurologic toxicity (17%). The median PEG-IFN-α-2b and ara-C doses delivered were 3 μg/kg weekly and 7.5 mg daily, respectively, at 12 months of therapy. The activity and toxicity profiles of this combination was similar to those observed in historical patients treated with IFN-α and cytarabine. CONCLUSIONS. The combination of PEG-IFN-α-2b and ara-C is active but has significant toxicity in patients with chronic-phase CML at the dose schedule used. The recommended dose of PEG-IFN-α-2b in future combination studies is 3 μg/kg or less.

Original languageEnglish (US)
Pages (from-to)3010-3016
Number of pages7
JournalCancer
Volume97
Issue number12
DOIs
StatePublished - Jun 15 2003
Externally publishedYes

Keywords

  • Chronic myelogenous leukemia
  • Cytogenetic response
  • Cytosine arabinoside
  • Polyethylene glycol interferon

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Garcia-Manero, G., Talpaz, M., Giles, F. J., Cortes, J., Faderl, S., O'Brien, S., Thomas, D., Verstovsek, S., Rios, M. B., Shan, J., Ferrajoli, A., Wierda, W., & Kantarjian, H. M. (2003). Treatment of Philadelphia chromosome-positive chronic myelogenous leukemia with weekly polyethylene glycol formulation of interferon-alpha-2b and low-dose cytosine arabinoside. Cancer, 97(12), 3010-3016. https://doi.org/10.1002/cncr.11424