title: Comparison of imatinib 400 mg and 800 mg daily in the front-line treatment of high-risk, Philadelphia-positive chronic myeloid leukemia: a European LeukemiaNet Study.
abstract: Imatinib mesylate (IM), 400 mg daily, is the standard treatment of Philadelphia-positive (Ph(+)) chronic myeloid leukemia (CML). Preclinical data and results of single-arm studies raised the suggestion that better results could be achieved with a higher dose. To investigate whether the systematic use of a higher dose of IM could lead to better results, 216 patients with Ph(+) CML at high risk (HR) according to the Sokal index were randomly assigned to receive IM 800 mg or 400 mg daily, as front-line therapy, for at least 1 year. The CCgR rate at 1 year was 64% and 58% for the high-dose arm and for the standard-dose arm, respectively (P = .435). No differences were detectable in the CgR at 3 and 6 months, in the molecular response rate at any time, as well as in the rate of other events. Twenty-four (94%) of 25 patients who could tolerate the full 800-mg dose achieved a CCgR, and only 4 (23%) of 17 patients who could tolerate less than 350 mg achieved a CCgR. This study does not support the extensive use of high-dose IM (800 mg daily) front-line in all CML HR patients. This trial was registered at www.clinicaltrials.gov as #NCT00514488.
authors.affiliation: Department of Hematology-Oncology L and A Seràgnoli, S Orsola-Malpighi University Hospital, Bologna, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Baccarani
authors.forename: Gianantonio
authors.initials: G
authors.lastname: Rosti
authors.forename: Fausto
authors.initials: F
authors.lastname: Castagnetti
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Haznedaroglu
authors.forename: Kimmo
authors.initials: K
authors.lastname: Porkka
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Abruzzese
authors.forename: Giuliana
authors.initials: G
authors.lastname: Alimena
authors.forename: Hans
authors.initials: H
authors.lastname: Ehrencrona
authors.forename: Henrik
authors.initials: H
authors.lastname: Hjorth-Hansen
authors.forename: Veli
authors.initials: V
authors.lastname: Kairisto
authors.forename: Luciano
authors.initials: L
authors.lastname: Levato
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
authors.forename: Johan
authors.initials: J
authors.lastname: Lanng Nielsen
authors.forename: Ugur
authors.initials: U
authors.lastname: Ozbek
authors.forename: Francesca
authors.initials: F
authors.lastname: Palandri
authors.forename: Fausto
authors.initials: F
authors.lastname: Palmieri
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Pane
authors.forename: Giovanna
authors.initials: G
authors.lastname: Rege-Cambrin
authors.forename: Domenico
authors.initials: D
authors.lastname: Russo
authors.forename: Giorgina
authors.initials: G
authors.lastname: Specchia
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Testoni
authors.forename: Ole
authors.initials: O
authors.lastname: Weiss-Bjerrum
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Saglio
authors.forename: Bengt
authors.initials: B
authors.lastname: Simonsson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides; D020732:Cytogenetic Analysis; D004305:Dose-Response Relationship, Drug; D005060:Europe; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage*; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000008:administration & dosage*; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl