title: High-dose imatinib induction followed by standard-dose maintenance in pre-treated chronic phase chronic myeloid leukemia patients--final analysis of a randomized, multicenter, phase III trial.
abstract: BACKGROUND
  Previous data suggest that the response of chronic myeloid leukemia cells to imatinib is dose-dependent. The potential benefit of initial dose intensification of imatinib in pre-treated patients with chronic phase chronic myeloid leukemia remains unknown.
  
  
  METHODS
  Two hundred and twenty-seven pre-treated patients with chronic myeloid leukemia in chronic phase were randomly assigned to continuous treatment with a standard dose of imatinib (400 mg/day; n=113) or to 6 months of high-dose induction with imatinib (800 mg/day) followed by a standard dose of imatinib as maintenance therapy (n=114).
  
  
  RESULTS
  The rates of major and complete cytogenetic responses were significantly higher in the high-dose arm than in the standard-dose arm at both 3 and 6 months (major cytogenetic responses: 36.8% versus 21.2%, P=0.01 and 50.0% versus 34.5%, P=0.018; complete cytogenetic responses: 22.8% versus 6.2%, P<0.001 and 40.4% versus 16.8%, P<0.001) on the basis of an intention-to-treat analysis. At 12 months, the difference between treatment arms remained statistically significant for complete cytogenetic responses (40.4% versus 24.8%, P=0.012) but not for major cytogenetic responses (49.1% versus 44.2%, P=0.462). The rate of major molecular responses was also significantly better at 3 and 6 months in the high-dose arm (month 3: 14.9% versus 3.5%, P=0.003; month 6: 32.5% versus 8.8%, P<0.001). Overall and progression-free survival rates were comparable between arms, but event-free survival was significantly worse in the high-dose arm (P=0.014).
  
  
  CONCLUSIONS
  Standard-dose imatinib remains the standard of care for pre-treated patients with chronic phase chronic myeloid leukemia (Clinicaltrials.gov identifier: NCT00327262).
authors.affiliation: Central European Leukemia Study Group, Internal Medicine V, Hematology and Oncology, Medical University Innsbruck, Innsbruck, Austria. andreas.petzer@bhs.at
authors.forename: Andreas L
authors.initials: AL
authors.lastname: Petzer
authors.forename: Dominic
authors.initials: D
authors.lastname: Fong
authors.forename: Thomas
authors.initials: T
authors.lastname: Lion
authors.forename: Irina
authors.initials: I
authors.lastname: Dyagil
authors.forename: Zvenyslava
authors.initials: Z
authors.lastname: Masliak
authors.forename: Andrija
authors.initials: A
authors.lastname: Bogdanovic
authors.forename: Laimonas
authors.initials: L
authors.lastname: Griskevicius
authors.forename: Sandra
authors.initials: S
authors.lastname: Lejniece
authors.forename: Stefan
authors.initials: S
authors.lastname: Goranov
authors.forename: Liana
authors.initials: L
authors.lastname: Gercheva
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Stojanovic
authors.forename: Dontcho
authors.initials: D
authors.lastname: Peytchev
authors.forename: Nikolay
authors.initials: N
authors.lastname: Tzvetkov
authors.forename: Rasa
authors.initials: R
authors.lastname: Griniute
authors.forename: Atanas
authors.initials: A
authors.lastname: Stanchev
authors.forename: Thomas
authors.initials: T
authors.lastname: Grubinger
authors.forename: Marthin
authors.initials: M
authors.lastname: Kwakkelstein
authors.forename: Peter
authors.initials: P
authors.lastname: Schuld
authors.forename: Guenther
authors.initials: G
authors.lastname: Gastl
authors.forename: Dominik
authors.initials: D
authors.lastname: Wolf
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D060828:Induction Chemotherapy; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000401:mortality; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate