title: Long-term outcome following imatinib therapy for chronic myelogenous leukemia, with assessment of dosage and blood levels: the JALSG CML202 study.
abstract: A prospective multicenter Phase II study was performed to examine the efficacy and safety of imatinib therapy in newly diagnosed Japanese patients with chronic-phase CML. Patients were scheduled to receive imatinib 400 mg daily. Plasma imatinib concentrations were measured by liquid chromatography-tandem mass spectrometry. In 481 evaluable patients, estimated 7-year overall survival (OS) and event-free survival (EFS) at a median follow-up of 65 months were 93% and 87%, respectively. Because imatinib dosage was reduced in many patients due mainly to adverse events, subgroup analysis was performed according to the mean daily dose during the first 24 months of treatment: ≥360 mg (400-mg group; n = 294), 270-359 mg (300-mg group; n = 90) and <270 mg (200-mg group; n = 67). There were no significant differences in OS and EFS between the 300- and 400-mg groups; however, cumulative rates of complete cytogenetic and major molecular responses differed significantly between the two groups. There were no significant differences in mean imatinib trough levels between these two groups for the patients in whom trough levels had been measured. Survival and efficacy in the 200-mg group were markedly inferior to the former two groups. These results suggest that, although a daily dose of 400 mg imatinib is associated with better outcomes, 300 mg imatinib may be adequate for a considerable number of Japanese patients who are intolerant to 400 mg imatinib. Blood level monitoring would be useful to determine the optimal dose of imatinib.
authors.affiliation: Oncology Center, Hamamatsu University School of Medicine, Hamamatsu, Japan. kohnishi@hama-med.ac.jp
authors.forename: Kazunori
authors.initials: K
authors.lastname: Ohnishi
authors.forename: Chiaki
authors.initials: C
authors.lastname: Nakaseko
authors.forename: Jin
authors.initials: J
authors.lastname: Takeuchi
authors.forename: Shin
authors.initials: S
authors.lastname: Fujisawa
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nagai
authors.forename: Hirohito
authors.initials: H
authors.lastname: Yamazaki
authors.forename: Tetsuzo
authors.initials: T
authors.lastname: Tauchi
authors.forename: Kiyotoshi
authors.initials: K
authors.lastname: Imai
authors.forename: Naoki
authors.initials: N
authors.lastname: Mori
authors.forename: Fumiharu
authors.initials: F
authors.lastname: Yagasaki
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Maeda
authors.forename: Noriko
authors.initials: N
authors.lastname: Usui
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: Koichi
authors.initials: K
authors.lastname: Miyamura
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kiyoi
authors.forename: Shigeki
authors.initials: S
authors.lastname: Ohtake
authors.forename: Tomoki
authors.initials: T
authors.lastname: Naoe
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000097:blood* / Q000627:therapeutic use; D001549:Benzamides; D018450:Disease Progression; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage* / Q000097:blood* / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011743:Pyrimidines / Q000008:administration & dosage* / Q000097:blood* / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl