Correlation between imatinib pharmacokinetics and clinical response in Japanese patients with chronic-phase chronic myeloid leukemia.
Despite the outstanding results generally obtained with imatinib mesylate (IM) in the treatment of chronic myeloid leukemia (CML), some patients show a poor molecular response. To evaluate the relationship between steady-state trough plasma IM concentration (IM-C(min)) and clinical response in CML patients, we integrated data from six independent Japanese studies. Among 254 CML patients, the mean IM-C(min) was 1,010.5 ng/ml. Importantly, IM-C(min) was significantly higher in patients who achieved a major molecular response (MMR) than in those who did not (P = 0.002). Multivariate analysis showed that an MMR was associated with both age (odds ratio (OR) = 0.97 (0.958-0.995); P = 0.0153) and with IM-C(min) (OR = 1.0008 (1.0003-1.0015); P = 0.0044). Given that patients with IM-C(min) values >1,002 ng/ml had a higher probability of achieving an MMR in our large cohort (P = 0.0120), the data suggest that monitoring of IM levels in plasma may improve the efficacy of IM therapy for CML patients.
Takahashi
N
N
Department of Hematology, Nephrology, and Rheumatology, Akita University Graduate School of Medicine, Akita, Japan. naotot@doc.med.akita-u.ac.jp
Wakita
H
H
Miura
M
M
Scott
S A
SA
Nishii
K
K
Masuko
M
M
Sakai
M
M
Maeda
Y
Y
Ishige
K
K
Kashimura
M
M
Fujikawa
K
K
Fukazawa
M
M
Katayama
T
T
Monma
F
F
Narita
M
M
Urase
F
F
Furukawa
T
T
Miyazaki
Y
Y
Katayama
N
N
Sawada
K
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D001549:Benzamides; D015331:Cohort Studies; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D011743:Pyrimidines / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate