Dasatinib or high-dose imatinib for chronic-phase chronic myeloid leukemia after failure of first-line imatinib: a randomized phase 2 trial.
Therapeutic options for chronic myelogenous leukemia (CML) resistant to 400 to 600 mg imatinib are limited. Escalating imatinib doses may overcome resistance. Dasatinib, a significantly more potent inhibitor of BCR-ABL, is safe and effective in this population. Patients with imatinib-resistant chronic-phase (CP) CML were randomized 2:1 to 140 mg dasatinib (n=101) or 800 mg imatinib (n=49). With a median follow up of 15 months, complete hematologic responses were observed in 93% and 82% of patients receiving dasatinib and high-dose imatinib (P=.034), respectively. Dasatinib resulted in higher major cytogenetic response rates (52%) than high-dose imatinib (33%) (P=.023); this included complete cytogenetic response in 40% and 16% (P=.004). Major molecular responses were also more frequent with dasatinib (16% versus 4%; P=0.038). Treatment failure (hazard ratio [HR], 0.16; P<.001) and progression-free survival (HR, 0.14; P<.001) both favored dasatinib. Superficial edema (42% versus 15%) and fluid retention (45% versus 30%) were more prevalent with imatinib; pleural effusion was more common with dasatinib (17% versus 0%). Grade 3 to 4 nonhematologic toxicity was minimal. Cytopenias were more frequent and severe with dasatinib. Dasatinib represents a safe and effective therapy for CP-CML resistant to conventional imatinib doses with improved cytogenetic and molecular response rates and progression-free survival relative to high-dose imatinib.
Kantarjian
Hagop
H
Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, TX 77230-1402, USA. hkantarj@mdanderson.org
Pasquini
Ricardo
R
Hamerschlak
Nelson
N
Rousselot
Philippe
P
Holowiecki
Jerzy
J
Jootar
Saengsuree
S
Robak
Tadeusz
T
Khoroshko
Nina
N
Masszi
Tamas
T
Skotnicki
Aleksander
A
Hellmann
Andrzej
A
Zaritsky
Andrey
A
Golenkov
Anatoly
A
Radich
Jerald
J
Hughes
Timothy
T
Countouriotis
Athena
A
Shah
Neil
N
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides; D020732:Cytogenetic Analysis; D000069439:Dasatinib; D018572:Disease-Free Survival; D004351:Drug Resistance; D004487:Edema / Q000139:chemically induced; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D015466:Leukemia, Myeloid, Chronic-Phase / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010198:Pancytopenia / Q000139:chemically induced; D010879:Piperazines / Q000008:administration & dosage* / Q000633:toxicity; D010996:Pleural Effusion / Q000139:chemically induced; D011743:Pyrimidines / Q000008:administration & dosage* / Q000633:toxicity; D016879:Salvage Therapy / Q000379:methods*; D013844:Thiazoles / Q000008:administration & dosage* / Q000633:toxicity; D016896:Treatment Outcome
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D000069439:Dasatinib