Phase 1 study of polyethylene glycol formulation of interferon α-2B (Schering 54031) in Philadelphia chromosome-positive chronic myelogenous leukemia

Moshe Talpaz, Susan O'Brien, Esther Rose, Samir Gupta, Jianqin Shan, Jorge Cortes, Francis J. Giles, Stefan Faderl, Hagop M. Kantarjian

Research output: Contribution to journalArticle

Abstract

Interferon α (IFN-α) therapy improves prognosis in Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML). Polyethylene glycol (PEG) attached to IFN-α prolongs its half-life and may offer better therapy. The aims of this phase 1 study were to define the maximal tolerated dose (MTD), dose-limiting toxicities (DLTs), and response with PEG IFN-α2b. Twenty-seven adults with Ph+ CML in chronic or accelerated phases, in whom IFN-α treatment had failed, were studied. Patients had hematologic (9 patients) or cytogenetic resistance (12 patients) or intolerance to IFN-α (6 patients). PEG IFN-α-2b was given as a weekly subcutaneous injection starting at 0.75 μg/kg weekly and escalating to 1.5, 3, 4.5, 6, 7.5, and 9.0 μg/kg. The MTD was defined at 7.5 to 9 μg/kg; DLT included severe fatigue, neurotoxicity, liver function abnormalities, and myelosuppression. Longer administration of PEG IFN-α-2b resulted in chronic side effects not observed earlier, which defined the MTD and DLT. The proposed phase 2 dose of PEG IFN-α-2b was 6 μg/kg weekly. Among 19 patients with active disease, 7 (37%) achieved complete hematologic response (CHR); 2 (11%) had a cytogenetic response (complete). Among 8 patients treated in CHR, 7 (87%) improved cytogenetic response to complete (4 patients) or partial (3 patients). All 6 patients intolerant to IFN-α tolerated PEG IFN-α-2b; 4 improved their cytogenetic response. The results show that PEG IFN-α-2b is easier to deliver (once weekly), better tolerated, and perhaps more effective than IFN-α.

Original languageEnglish (US)
Pages (from-to)1708-1713
Number of pages6
JournalBlood
Volume98
Issue number6
DOIs
StatePublished - Sep 15 2001

Fingerprint

Philadelphia Chromosome
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Chromosomes
Interferons
Cytogenetics
Maximum Tolerated Dose
Toxicity
Liver
Subcutaneous Injections
Fatigue of materials
Fatigue
Half-Life
Therapeutics

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Phase 1 study of polyethylene glycol formulation of interferon α-2B (Schering 54031) in Philadelphia chromosome-positive chronic myelogenous leukemia. / Talpaz, Moshe; O'Brien, Susan; Rose, Esther; Gupta, Samir; Shan, Jianqin; Cortes, Jorge; Giles, Francis J.; Faderl, Stefan; Kantarjian, Hagop M.

In: Blood, Vol. 98, No. 6, 15.09.2001, p. 1708-1713.

Research output: Contribution to journalArticle

Talpaz, Moshe ; O'Brien, Susan ; Rose, Esther ; Gupta, Samir ; Shan, Jianqin ; Cortes, Jorge ; Giles, Francis J. ; Faderl, Stefan ; Kantarjian, Hagop M. / Phase 1 study of polyethylene glycol formulation of interferon α-2B (Schering 54031) in Philadelphia chromosome-positive chronic myelogenous leukemia. In: Blood. 2001 ; Vol. 98, No. 6. pp. 1708-1713.
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