title: Correlation of plasma crizotinib trough concentration with adverse events in patients with anaplastic lymphoma kinase positive non-small-cell lung cancer.
abstract: 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.
  
  
  RESULTS
  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 847.8 ng/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.
authors.affiliation: Department of Pharmacy, Okayama University Hospital, Okayama, 700-8558 Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Kurata
authors.affiliation: Department of Oncology Pharmaceutical Care & Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, 700-8530 Japan.
authors.forename: Narumi
authors.initials: N
authors.lastname: Miyauchi
authors.affiliation: Department of Oncology Pharmaceutical Care & Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, 700-8530 Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Suno
authors.affiliation: Department of Oncology Pharmaceutical Care & Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, 700-8530 Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ito
authors.affiliation: Department of Pharmacy, Okayama University Hospital, Okayama, 700-8558 Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Sendo
authors.affiliation: Department of Allergy and Respiratory, Okayama University Hospital, Okayama, 700-8558 Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kiura
keywords: Adverse events; Crizotinib; LC-MS/MS; Therapeutic drug monitoring
references.citation: Lancet Oncol. 2012 Oct;13(10):1011-9
references.pmid: 22954507
references.citation: J Pathol. 2014 Jan;232(2):121-33
references.pmid: 24114583
references.citation: Mol Clin Oncol. 2013 Jul;1(4):575-581
references.pmid: 24649213
references.citation: J Med Chem. 2011 Sep 22;54(18):6342-63
references.pmid: 21812414
references.citation: Eur J Cancer. 2012 May;48(7):961-73
references.pmid: 22397764
references.citation: Clin Cancer Res. 2008 Jul 1;14(13):4275-83
references.pmid: 18594010
references.citation: N Engl J Med. 2013 Jun 20;368(25):2385-94
references.pmid: 23724913
references.citation: Am J Health Syst Pharm. 2013 Jun 1;70(11):943-7
references.pmid: 23686600
references.citation: N Engl J Med. 2010 Oct 28;363(18):1693-703
references.pmid: 20979469
references.citation: Clin Cancer Res. 2012 Jul 15;18(14):3737-42
references.pmid: 22547770
references.citation: Nature. 2007 Aug 2;448(7153):561-6
references.pmid: 17625570
references.citation: Drug Des Devel Ther. 2011;5:471-85
references.pmid: 22162641
references.citation: Lancet Oncol. 2011 Feb;12(2):175-80
references.pmid: 21277552