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.
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.
Baccarani
Michele
M
Department of Hematology-Oncology L and A Seràgnoli, S Orsola-Malpighi University Hospital, Bologna, Italy.
Rosti
Gianantonio
G
Castagnetti
Fausto
F
Haznedaroglu
Ibrahim
I
Porkka
Kimmo
K
Abruzzese
Elisabetta
E
Alimena
Giuliana
G
Ehrencrona
Hans
H
Hjorth-Hansen
Henrik
H
Kairisto
Veli
V
Levato
Luciano
L
Martinelli
Giovanni
G
Nagler
Arnon
A
Lanng Nielsen
Johan
J
Ozbek
Ugur
U
Palandri
Francesca
F
Palmieri
Fausto
F
Pane
Fabrizio
F
Rege-Cambrin
Giovanna
G
Russo
Domenico
D
Specchia
Giorgina
G
Testoni
Nicoletta
N
Weiss-Bjerrum
Ole
O
Saglio
Giuseppe
G
Simonsson
Bengt
B
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
D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl