TY - JOUR
T1 - Correlation of plasma crizotinib trough concentration with adverse events in patients with anaplastic lymphoma kinase positive non-small-cell lung cancer
AU - Kurata, Yasuko
AU - Miyauchi, Narumi
AU - Suno, Manabu
AU - Ito, Takahiro
AU - Sendo, Toshiaki
AU - Kiura, Katsuyuki
N1 - Publisher Copyright:
© 2014 Kurata et al. licensee BioMed Central Ltd.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2015/3/2
Y1 - 2015/3/2
N2 - Background: Crizotinib, an ATP-competitive receptor tyrosine kinase inhibitor of both anaplastic lymphoma kinase (ALK) and the hepatocyte growth factor receptor, commonly causes several adverse events (AEs). The clinical utility of measuring the plasma concentration of crizotinib in patients with non-small-cell lung cancer (NSCLC) has not been fully elucidated. The aim of this study was to evaluate the variability in the crizotinib trough concentration and its relationship with the occurrence of AEs in NSCLC patients. Findings: Plasma samples were collected from 9 ALK fusion gene-positive NSCLC Japanese patients at day 14 after the first administration of crizotinib. We assessed crizotinib-induced AEs on days 7, 14, 21, and 28. The crizotinib trough concentration on day 14 ranged from 243.5 to 847.8ng/mL, and all of the patients achieved stable disease based on assessment of the tumor response on day 28. The cumulative number of AEs on day 28 in the higher trough concentration group was approximately 3-fold greater than that in the lower trough concentration group. AEs of grade 3 or 4 were observed only in patients in the higher trough concentration group. Conclusions: The occurrence of several AEs may correlate with the increase in the crizotinib trough concentration. Monitoring of the crizotinib trough concentration could predict the risk of development of several AEs and provide guidance for determining the optimal dose of crizotinib.
AB - Background: Crizotinib, an ATP-competitive receptor tyrosine kinase inhibitor of both anaplastic lymphoma kinase (ALK) and the hepatocyte growth factor receptor, commonly causes several adverse events (AEs). The clinical utility of measuring the plasma concentration of crizotinib in patients with non-small-cell lung cancer (NSCLC) has not been fully elucidated. The aim of this study was to evaluate the variability in the crizotinib trough concentration and its relationship with the occurrence of AEs in NSCLC patients. Findings: Plasma samples were collected from 9 ALK fusion gene-positive NSCLC Japanese patients at day 14 after the first administration of crizotinib. We assessed crizotinib-induced AEs on days 7, 14, 21, and 28. The crizotinib trough concentration on day 14 ranged from 243.5 to 847.8ng/mL, and all of the patients achieved stable disease based on assessment of the tumor response on day 28. The cumulative number of AEs on day 28 in the higher trough concentration group was approximately 3-fold greater than that in the lower trough concentration group. AEs of grade 3 or 4 were observed only in patients in the higher trough concentration group. Conclusions: The occurrence of several AEs may correlate with the increase in the crizotinib trough concentration. Monitoring of the crizotinib trough concentration could predict the risk of development of several AEs and provide guidance for determining the optimal dose of crizotinib.
KW - Adverse events
KW - Crizotinib
KW - LC-MS/MS
KW - Therapeutic drug monitoring
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U2 - 10.1186/s40780-014-0008-x
DO - 10.1186/s40780-014-0008-x
M3 - Article
AN - SCOPUS:84975304105
VL - 1
JO - Journal of Pharmaceutical Health Care and Sciences
JF - Journal of Pharmaceutical Health Care and Sciences
SN - 2055-0294
IS - 1
M1 - 8
ER -