title: Dasatinib in the treatment of chronic myeloid leukemia in accelerated phase after imatinib failure: the START a trial.
abstract: PURPOSE Patients with chronic myelogenous leukemia in accelerated phase (CML-AP) that is resistant or intolerant to imatinib have limited therapeutic options. Dasatinib, a potent inhibitor of BCR-ABL and SRC-family kinases, has efficacy in patients with CML-AP who have experienced treatment failure with imatinib. We now report follow-up data from the full patient cohort of 174 patients enrolled onto a phase II trial to provide a more complete assessment of the efficacy and safety of dasatinib in this population. PATIENTS AND METHODS Patients with imatinib-resistant (n = 161) or -intolerant (n = 13) CML-AP received dasatinib 70 mg orally twice daily. Results At a median follow-up of 14.1 months (treatment duration, 0.1 to 21.7 months), major and complete hematologic responses were attained by 64% and 45% of patients, respectively, and major and complete cytogenetic responses were achieved in 39% and 32% of patients, respectively. Responses were achieved irrespective of imatinib status (resistant or intolerant), prior stem-cell transplantation, or the presence of prior BCR-ABL mutation. The 12-month progression-free survival and overall survival rates were 66% and 82%, respectively. Dasatinib was generally well tolerated; the most frequent nonhematologic severe treatment-related adverse event was diarrhea (52%; grade 3 to 4, 8%). Cytopenias were common, including grade 3 to 4 neutropenia (76%) and thrombocytopenia (82%). Pleural effusion occurred in 27% of patients (grade 3 to 4, 5%). CONCLUSION Dasatinib is effective in patients with CML-AP after imatinib treatment failure.
authors.affiliation: Hammersmith Hospital, Imperial College School of Medicine, Du Cane Rd, London W12 0NN, United Kingdom. j.apperley@imperial.ac.uk
authors.forename: Jane F
authors.initials: JF
authors.lastname: Apperley
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Cortes
authors.forename: Dong-Wook
authors.initials: DW
authors.lastname: Kim
authors.forename: Lydia
authors.initials: L
authors.lastname: Roy
authors.forename: Gail J
authors.initials: GJ
authors.lastname: Roboz
authors.forename: Gianantonio
authors.initials: G
authors.lastname: Rosti
authors.forename: Eduardo O
authors.initials: EO
authors.lastname: Bullorsky
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Abruzzese
authors.forename: Andreas
authors.initials: A
authors.lastname: Hochhaus
authors.forename: Dominik
authors.initials: D
authors.lastname: Heim
authors.forename: Carmino A
authors.initials: CA
authors.lastname: de Souza
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Lipton
authors.forename: H Jean
authors.initials: HJ
authors.lastname: Khoury
authors.forename: Hyeoung-Joon
authors.initials: HJ
authors.lastname: Kim
authors.forename: Christian
authors.initials: C
authors.lastname: Sillaber
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Hughes
authors.forename: Philipp
authors.initials: P
authors.lastname: Erben
authors.forename: Jan
authors.initials: J
authors.lastname: Van Tornout
authors.forename: Richard M
authors.initials: RM
authors.lastname: Stone
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides; D000069439:Dasatinib; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D011743:Pyrimidines / Q000627:therapeutic use*; D013844:Thiazoles / Q000627:therapeutic use*; D017211:Treatment Failure; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D000069439:Dasatinib