title: Dasatinib induces durable cytogenetic responses in patients with chronic myelogenous leukemia in chronic phase with resistance or intolerance to imatinib.
abstract: Dasatinib, a potent inhibitor of BCR-ABL in vitro, is effective for patients with chronic myelogenous leukemia (CML) resistant or intolerant to imatinib. To provide a more definitive assessment of dasatinib in chronic-phase (CP)-CML, we report extended follow-up of a phase II trial, presenting data for the entire patient cohort (N=387). Dasatinib (70 mg) twice daily was administered to patients with imatinib-resistant or -intolerant CP-CML. With median follow-up of 15.2 months (treatment duration, <1-18.4 months), a complete hematologic response was attained or maintained in 91% of patients. A major cytogenetic response (MCyR) was attained or maintained by 59% (52% imatinib resistant and 80% imatinib intolerant); this was complete in 49% of patients (40% imatinib resistant and 75% imatinib intolerant). Of 230 patients achieving an MCyR, 7 experienced disease progression. Fifteen-month progression-free survival was 90% while overall survival was 96%. Grade 3/4 thrombocytopenia and neutropenia were reported in 48 and 49% of patients, respectively. Non-hematologic toxicity (any grade) consisted primarily of diarrhea (37%), headache (32%), fatigue (31%), dyspnea (30%) and pleural effusion (27%). Pleural effusions were classified as grade 3 in 6% of reported events, with no incidence of grade 4. Dasatinib is associated with high response rates in patients with imatinib-resistant or -intolerant CP-CML.
authors.affiliation: III Medizinische Klinik, Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim, Germany. hochhaus@uni-hd.de
authors.forename: A
authors.initials: A
authors.lastname: Hochhaus
authors.forename: M
authors.initials: M
authors.lastname: Baccarani
authors.forename: M
authors.initials: M
authors.lastname: Deininger
authors.forename: J F
authors.initials: JF
authors.lastname: Apperley
authors.forename: J H
authors.initials: JH
authors.lastname: Lipton
authors.forename: S L
authors.initials: SL
authors.lastname: Goldberg
authors.forename: S
authors.initials: S
authors.lastname: Corm
authors.forename: N P
authors.initials: NP
authors.lastname: Shah
authors.forename: F
authors.initials: F
authors.lastname: Cervantes
authors.forename: R T
authors.initials: RT
authors.lastname: Silver
authors.forename: D
authors.initials: D
authors.lastname: Niederwieser
authors.forename: R M
authors.initials: RM
authors.lastname: Stone
authors.forename: H
authors.initials: H
authors.lastname: Dombret
authors.forename: R A
authors.initials: RA
authors.lastname: Larson
authors.forename: L
authors.initials: L
authors.lastname: Roy
authors.forename: T
authors.initials: T
authors.lastname: Hughes
authors.forename: M C
authors.initials: MC
authors.lastname: Müller
authors.forename: R
authors.initials: R
authors.lastname: Ezzeddine
authors.forename: A M
authors.initials: AM
authors.lastname: Countouriotis
authors.forename: H M
authors.initials: HM
authors.lastname: Kantarjian
mesh_terms: D000328:Adult; D000368:Aged; D001549:Benzamides; D000069439:Dasatinib; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; 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; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010879:Piperazines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000627:therapeutic use*; D015996:Survival Rate; D013844:Thiazoles / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl; D000069439:Dasatinib