title: Interferon-alpha-2b and oral cytarabine ocfosfate for newly diagnosed chronic myeloid leukaemia.
abstract: BACKGROUND
  Treatment with interferon and subcutaneous cytarabine produces superior cytogenetic responses in chronic myeloid leukaemia (CML) than treatment with interferon alone, but at the expense of greater toxicity. Cytarabine ocfosfate (YNK01) is an oral precursor of cytarabine that may overcome some of the inconvenience and toxicities associated with subcutaneous cytarabine administration.
  
  
  METHODS
  We studied the efficacy and tolerability of combination therapy with interferon-alpha-2b and YNK01 in patients with newly diagnosed, untreated CML. Forty patients were treated with interferon-alpha-2b (5 MU/m2/day) plus monthly courses of YNK01 (600 mg/day for 10 days) for 1 year.
  
  
  RESULTS
  The 6-month complete haematological response rate was 63% and the 1-year major cytogenetic response rate was 30%, with 10% of cytogenetic responses being complete. With a median follow-up of 57 months, the estimated 5-year overall survival was 86% (95% confidence interval 70% to 94%). Treatment tolerability was poor, with toxicity leading to discontinuation of one or both drugs in 60% of cases. The median daily dose of interferon alpha-2b was 7.75 MU and the median dose of YNK01 was 600 mg/day for each 10-day treatment cycle.
  
  
  CONCLUSIONS
  Interferon-alpha-2b and YNK01 produce cytogenetic responses comparable to those achieved with interferon-alpha-2b and parenteral cytarabine, although toxicity was excessive. Alternate dosing strategies may enhance the tolerability of YNK01.
authors.affiliation: Haematology Department, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia. peter_mollee@health.qld.gov.au
authors.forename: P
authors.initials: P
authors.lastname: Mollee
authors.forename: C
authors.initials: C
authors.lastname: Arthur
authors.forename: T
authors.initials: T
authors.lastname: Hughes
authors.forename: H
authors.initials: H
authors.lastname: Januszewicz
authors.forename: A
authors.initials: A
authors.lastname: Grigg
authors.forename: K
authors.initials: K
authors.lastname: Bradstock
authors.forename: M
authors.initials: M
authors.lastname: Wolf
authors.forename: J
authors.initials: J
authors.lastname: Gibson
authors.forename: A P
authors.initials: AP
authors.lastname: Schwarer
authors.forename: A
authors.initials: A
authors.lastname: Spencer
authors.forename: P
authors.initials: P
authors.lastname: Browett
authors.forename: T
authors.initials: T
authors.lastname: Hawkins
authors.forename: M
authors.initials: M
authors.lastname: Seldon
authors.forename: R
authors.initials: R
authors.lastname: Herrmann
authors.forename: A
authors.initials: A
authors.lastname: Watson
authors.forename: J F
authors.initials: JF
authors.lastname: Seymour
authors.forename: N
authors.initials: N
authors.lastname: Martin
authors.forename: S
authors.initials: S
authors.lastname: Shina
authors.forename: C
authors.initials: C
authors.lastname: Low
authors.forename: S
authors.initials: S
authors.lastname: Wright
authors.forename: R
authors.initials: R
authors.lastname: Rodwell
authors.forename: J
authors.initials: J
authors.lastname: Coulston
authors.forename: J
authors.initials: J
authors.lastname: Morton
authors.forename: H
authors.initials: H
authors.lastname: Blacklock
authors.forename: D
authors.initials: D
authors.lastname: Taylor
authors.forename: K M
authors.initials: KM
authors.lastname: Taylor
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D001088:Arabinonucleotides / Q000008:administration & dosage; D003568:Cytidine Monophosphate / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D016896:Treatment Outcome
chemical_list: D001088:Arabinonucleotides; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; C061162:1-arabinofuranosylcytosine-5'-stearylphosphate; D003568:Cytidine Monophosphate