title: Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia.
abstract: BACKGROUND
  Imatinib, a selective inhibitor of the BCR-ABL tyrosine kinase, produces high response rates in patients with chronic-phase chronic myeloid leukemia (CML) who have had no response to interferon alfa. We compared the efficacy of imatinib with that of interferon alfa combined with low-dose cytarabine in newly diagnosed chronic-phase CML.
  
  
  METHODS
  We randomly assigned 1106 patients to receive imatinib (553 patients) or interferon alfa plus low-dose cytarabine (553 patients). Crossover to the alternative group was allowed if stringent criteria defining treatment failure or intolerance were met. Patients were evaluated for hematologic and cytogenetic responses, toxic effects, and rates of progression.
  
  
  RESULTS
  After a median follow-up of 19 months, the estimated rate of a major cytogenetic response (0 to 35 percent of cells in metaphase positive for the Philadelphia chromosome) at 18 months was 87.1 percent (95 percent confidence interval, 84.1 to 90.0) in the imatinib group and 34.7 percent (95 percent confidence interval, 29.3 to 40.0) in the group given interferon alfa plus cytarabine (P<0.001). The estimated rates of complete cytogenetic response were 76.2 percent (95 percent confidence interval, 72.5 to 79.9) and 14.5 percent (95 percent confidence interval, 10.5 to 18.5), respectively (P<0.001). At 18 months, the estimated rate of freedom from progression to accelerated-phase or blast-crisis CML was 96.7 percent in the imatinib group and 91.5 percent in the combination-therapy group (P<0.001). Imatinib was better tolerated than combination therapy.
  
  
  CONCLUSIONS
  In terms of hematologic and cytogenetic responses, tolerability, and the likelihood of progression to accelerated-phase or blast-crisis CML, imatinib was superior to interferon alfa plus low-dose cytarabine as first-line therapy in newly diagnosed chronic-phase CML.
authors.affiliation: University of Newcastle, Newcastle, United Kingdom.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: O'Brien
authors.forename: François
authors.initials: F
authors.lastname: Guilhot
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
authors.forename: Insa
authors.initials: I
authors.lastname: Gathmann
authors.forename: Michele
authors.initials: M
authors.lastname: Baccarani
authors.forename: Francisco
authors.initials: F
authors.lastname: Cervantes
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Cornelissen
authors.forename: Thomas
authors.initials: T
authors.lastname: Fischer
authors.forename: Andreas
authors.initials: A
authors.lastname: Hochhaus
authors.forename: Timothy
authors.initials: T
authors.lastname: Hughes
authors.forename: Klaus
authors.initials: K
authors.lastname: Lechner
authors.forename: Johan L
authors.initials: JL
authors.lastname: Nielsen
authors.forename: Philippe
authors.initials: P
authors.lastname: Rousselot
authors.forename: Josy
authors.initials: J
authors.lastname: Reiffers
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Saglio
authors.forename: John
authors.initials: J
authors.lastname: Shepherd
authors.forename: Bengt
authors.initials: B
authors.lastname: Simonsson
authors.forename: Alois
authors.initials: A
authors.lastname: Gratwohl
authors.forename: John M
authors.initials: JM
authors.lastname: Goldman
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Kerry
authors.initials: K
authors.lastname: Taylor
authors.forename: Gregor
authors.initials: G
authors.lastname: Verhoef
authors.forename: Ann E
authors.initials: AE
authors.lastname: Bolton
authors.forename: Renaud
authors.initials: R
authors.lastname: Capdeville
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Druker
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001549:Benzamides; D003561:Cytarabine / Q000008:administration & dosage; D018450:Disease Progression; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D016898:Interferon-alpha / Q000008:administration & dosage; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D011446:Prospective Studies; D011743:Pyrimidines / Q000627:therapeutic use*; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D016898:Interferon-alpha; D010879:Piperazines; D011743:Pyrimidines; D003561:Cytarabine; D000068877:Imatinib Mesylate