title: Dasatinib induces fast and deep responses in newly diagnosed chronic myeloid leukaemia patients in chronic phase: clinical results from a randomised phase-2 study (NordCML006).
abstract: We randomised 46 newly diagnosed patients with chronic myeloid leukaemia (median age 56) to receive dasatinib 100 mg QD or imatinib 400 mg QD and report outcome as an intention-to-treat analysis with 36 months follow-up. Early cytogenetic and molecular responses were superior in the dasatinib group, with a tendency that imatinib patients caught up with time. For instance, MR(3.0) was reached at 3 months in 36% vs. 8% (P = 0.02), at 12 months in 81% vs. 46% (P = 0.02) and at 18 months in 73% vs. 65% (n.s.) of the patients in the two groups. In contrast, MR(4.5) was consistently superior in the dasatinib group at all time points from 6 months onwards, reaching 61% vs. 21% (P < 0.05) at 36 months. Sixty-four vs. 71% of the patients in the dasatinib and imatinib arms, respectively, remained on assigned drug. Dasatinib dose was frequently reduced, but with maintained excellent effect. One imatinib patient progressed to blastic phase, but no CML-related deaths occurred. In conclusion, our data compare favourably with those of the dasatinib registration study, DASISION. The fast and deep molecular responses induced by dasatinib compared with imatinib may be exploited to increase the proportion of patients who can achieve a treatment-free remission after treatment discontinuation.
authors.affiliation: Department of Hematology, St Olavs Hospital, Trondheim, Norway; Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
authors.forename: Henrik
authors.initials: H
authors.lastname: Hjorth-Hansen
authors.forename: Leif
authors.initials: L
authors.lastname: Stenke
authors.forename: Stina
authors.initials: S
authors.lastname: Söderlund
authors.forename: Arta
authors.initials: A
authors.lastname: Dreimane
authors.forename: Hans
authors.initials: H
authors.lastname: Ehrencrona
authors.forename: Tobias
authors.initials: T
authors.lastname: Gedde-Dahl
authors.forename: Bjørn Tore
authors.initials: BT
authors.lastname: Gjertsen
authors.forename: Martin
authors.initials: M
authors.lastname: Höglund
authors.forename: Perttu
authors.initials: P
authors.lastname: Koskenvesa
authors.forename: Kourosh
authors.initials: K
authors.lastname: Lotfi
authors.forename: Waleed
authors.initials: W
authors.lastname: Majeed
authors.forename: Berit
authors.initials: B
authors.lastname: Markevärn
authors.forename: Lotta
authors.initials: L
authors.lastname: Ohm
authors.forename: Ulla
authors.initials: U
authors.lastname: Olsson-Strömberg
authors.forename: Kari
authors.initials: K
authors.lastname: Remes
authors.forename: Merja
authors.initials: M
authors.lastname: Suominen
authors.forename: Bengt
authors.initials: B
authors.lastname: Simonsson
authors.forename: Kimmo
authors.initials: K
authors.lastname: Porkka
authors.forename: Satu
authors.initials: S
authors.lastname: Mustjoki
authors.forename: Johan
authors.initials: J
authors.lastname: Richter
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides / Q000627:therapeutic use*; D000069439:Dasatinib; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D012074:Remission Induction; D012306:Risk; D016019:Survival Analysis; D013844:Thiazoles / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; C581634:BCR-ABL1 fusion protein, human; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; D000069439:Dasatinib; D006918:Hydroxyurea
keywords: dasatinib; deep response; imatinib; randomized controlled trial; toxicity
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