title: Phase III, randomized, open-label study of daily imatinib mesylate 400 mg versus 800 mg in patients with newly diagnosed, previously untreated chronic myeloid leukemia in chronic phase using molecular end points: tyrosine kinase inhibitor optimization and selectivity study.
abstract: OBJECTIVE
  To evaluate the safety and efficacy of initial treatment with imatinib mesylate 800 mg/d (400 mg twice daily) versus 400 mg/d in patients with newly diagnosed chronic myeloid leukemia in chronic phase.
  
  
  METHODS
  A total of 476 patients were randomly assigned 2:1 to imatinib 800 mg (n = 319) or 400 mg (n = 157) daily. The primary end point was the major molecular response (MMR) rate at 12 months.
  
  
  RESULTS
  At 12 months, differences in MMR and complete cytogenetic response (CCyR) rates were not statistically significant (MMR, 46% v 40%; P = .2035; CCyR, 70% v 66%; P = .3470). However, MMR occurred faster among patients randomly assigned to imatinib 800 mg/d, who had higher rates of MMR at 3 and 6 months compared with those in the imatinib 400-mg/d arm (P = .0035 by log-rank test). CCyR also occurred faster in the 800-mg/d arm (CCyR at 6 months, 57% v 45%; P = .0146). The most common adverse events were edema, gastrointestinal problems, and rash, and all were more common in patients in the 800-mg/d arm. Grades 3 to 4 hematologic toxicity also occurred more frequently in patients receiving imatinib 800 mg/d.
  
  
  CONCLUSIONS
  MMR rates at 1 year were similar with imatinib 800 mg/d and 400 mg/d, but MMR and CCyR occurred earlier in patients treated with 800 mg/d. Continued follow-up is needed to determine the clinical significance of earlier responses on high-dose imatinib.
authors.affiliation: University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Jcortes@mdanderson.org
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Cortes
authors.forename: Michele
authors.initials: M
authors.lastname: Baccarani
authors.forename: François
authors.initials: F
authors.lastname: Guilhot
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Druker
authors.forename: Susan
authors.initials: S
authors.lastname: Branford
authors.forename: Dong-Wook
authors.initials: DW
authors.lastname: Kim
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Pane
authors.forename: Ricardo
authors.initials: R
authors.lastname: Pasquini
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Goldberg
authors.forename: Matt
authors.initials: M
authors.lastname: Kalaycio
authors.forename: Beatriz
authors.initials: B
authors.lastname: Moiraghi
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Rowe
authors.forename: Elena
authors.initials: E
authors.lastname: Tothova
authors.forename: Carmino
authors.initials: C
authors.lastname: De Souza
authors.forename: Marc
authors.initials: M
authors.lastname: Rudoltz
authors.forename: Richard
authors.initials: R
authors.lastname: Yu
authors.forename: Tillmann
authors.initials: T
authors.lastname: Krahnke
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: Jerald P
authors.initials: JP
authors.lastname: Radich
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Hughes
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001549:Benzamides; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D015466:Leukemia, Myeloid, Chronic-Phase / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000008:administration & dosage*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases