title: Adherence to the standard dose of imatinib, rather than dose adjustment based on its plasma concentration, is critical to achieve a deep molecular response in patients with chronic myeloid leukemia.
abstract: The correlation between imatinib (IM) trough plasma concentration (Cmin) and clinical response was assessed in patients with chronic-phase chronic myeloid leukemia. The Cmin correlated with neither the achievement of complete cytogenetic response (977 vs. 993 ng/ml, P = 0.48) nor a major molecular response (1,044 vs. 818 ng/ml, P = 0.17). Although this was significantly higher in patients with complete molecular response (CMR) than in those without (1,430 vs. 859 ng/ml, P = 0.04), the difference was not significant in the sub-population treated with a standard dose of IM (400 mg/day). Finally, multivariate analysis showed that the IM standard dose, but not Cmin, was predictive of the achievement of CMR. We thus suggest that, in practical clinics at least, adherence to the standard dose is the most important factor for the achievement of CMR.
authors.affiliation: Department of Hematology, National Hospital Organization Mito Medical Center, Higashiibarakigun, Japan.
authors.forename: Chikashi
authors.initials: C
authors.lastname: Yoshida
authors.affiliation: Department of Hematology, National Hospital Organization Mito Medical Center, Higashiibarakigun, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Komeno
authors.affiliation: Department of Hematology, Ibaraki Prefectural Central Hospital, Kasama, Japan.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Hori
authors.affiliation: Division of Hematology, Suifu Hospital, Mito, Japan.
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Division of Hematology, Suifu Hospital, Mito, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Fujii
authors.affiliation: Department of Clinical and Experimental Hematology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Okoshi
authors.affiliation: Department of Clinical and Experimental Hematology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Suzukawa
authors.affiliation: Department of Clinical and Experimental Hematology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Chiba
authors.affiliation: Department of Clinical and Experimental Hematology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hasegawa
authors.affiliation: Department of Clinical and Experimental Hematology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Harumi Yamamoto
authors.initials: HY
authors.lastname: Mukai
authors.affiliation: Department of Hematology, Toride Kyodo General Hospital, Toride, Japan.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Ito
authors.affiliation: Department of Hematology, Tsuchiura Kyodo General Hospital, Tsuchiura, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Shimizu
authors.affiliation: Department of Hematology, Tsuchiura Kyodo General Hospital, Tsuchiura, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Kamoshita
authors.affiliation: Department of Hematology, Hitachi General Hospital, Hitachi, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kudo
authors.affiliation: Department of Hematology, Hitachi General Hospital, Hitachi, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shinagawa
authors.affiliation: Department of Hematology, Hitachi General Hospital, Hitachi, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Chikatsu
authors.affiliation: Department of Hematology, Hitachi General Hospital, Hitachi, Japan.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Monma
authors.affiliation: Watanabe Naika Clinic, Hitachinaka, Japan.
authors.forename: Norimichi
authors.initials: N
authors.lastname: Watanabe
authors.affiliation: Department of Clinical Oncology, Ibaraki Prefectural Central Hospital, Kasama, Ibaraki, 309-1793, Japan. h-kojima@chubyoin.pref.ibaraki.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kojima
mesh_terms: D000368:Aged; D001549:Benzamides; D003430:Cross-Sectional Studies; D020732:Cytogenetic Analysis; D004305:Dose-Response Relationship, Drug; D054796:Drug Dosage Calculations; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors* / Q000097:blood / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D017404:In Situ Hybridization, Fluorescence; D007564:Japan; D015466:Leukemia, Myeloid, Chronic-Phase / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000097:blood / Q000235:genetics; D011743:Pyrimidines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012074:Remission Induction / Q000379:methods; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl