title: Treatment of Philadelphia chromosome-positive chronic myelogenous leukemia with weekly polyethylene glycol formulation of interferon-alpha-2b and low-dose cytosine arabinoside.
abstract: BACKGROUND
  To evaluate the activity and toxicity of weekly Schering 54301, a polyethylene glycol formulation of interferon- alpha-2b (PEG-IFN-alpha-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-alpha-2b and ara-C (10 mg daily subcutaneously [s.c.]). The starting dose of PEG-IFN-alpha-2b was 6 microg/kg s.c. weekly in the first 24 patients but was reduced to 4.5 microg/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-alpha-2b and ara-C doses delivered were 3 microg/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-alpha and cytarabine.
  
  
  CONCLUSIONS
  The combination of PEG-IFN-alpha-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-alpha-2b in future combination studies is 3 microg/kg or less.
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer, Houston, Texas 77030, USA. ggarciam@mdanderson.org
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Moshe
authors.initials: M
authors.lastname: Talpaz
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Giles
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Deborah
authors.initials: D
authors.lastname: Thomas
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.forename: Mary
authors.initials: M
authors.lastname: Beth Rios
authors.forename: Jianquin
authors.initials: J
authors.lastname: Shan
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ferrajoli
authors.forename: William
authors.initials: W
authors.lastname: Wierda
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity; D002908:Chronic Disease; D003561:Cytarabine / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D011994:Recombinant Proteins; D016896:Treatment Outcome
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D003561:Cytarabine; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a