title: Clinical implications of repeated drug monitoring of imatinib in patients with metastatic gastrointestinal stromal tumour.
abstract: BACKGROUND
  Imatinib mesylate (IM) is the preferred treatment for the majority of patients with metastatic gastrointestinal stromal tumour (GIST). Low trough IM concentration (Cmin) values have been associated with poor clinical outcomes in GIST patients. However, there are few studies of repeated measurements of IM levels, and therapeutic drug monitoring is not yet a part of routine clinical practice. This study was conducted to reveal clinical scenarios where plasma concentration measurement of IM trough level (Cmin) is advantageous.
  
  
  METHODS
  Patients with advanced GIST receiving IM were included from January 2011 to April 2015. Heparin plasma was collected at each follow-up visit. Ninety-six samples from 24 patients were selected for IM concentration measurement. Associations between IM plasma concentration and clinical variables were analyzed by Students' t test, univariate and multivariate linear regression analyses.
  
  
  RESULTS
  The mean IM Cminplasma concentrations for patients taking <400, 400 and >400 mg daily were 782, 1132 and 1665 ng/mL, respectively (p = 0.010). High IM Cminlevels were correlated with age, low body surface area, low haemoglobin concentration, low creatinine clearance, absence of liver metastasis and no prior gastric resection in univariate analysis. In multivariate analysis age, gastric resection and liver metastasis were included in the final model. Eight patients had disease progression during the study, and mean IM levels were significantly lower at time of progression compared to the previous measurement for the same patients (770 and 1223 ng/mL, respectively; p = 0.020).
  
  
  CONCLUSIONS
  Our results do not support repeated monitoring of IM levels on a routine basis in all patients. However, we have revealed clinical scenarios where drug measurement could be beneficial, such as for patients who have undergone gastric resection, suspicion of non-compliance, subjectively reported side effects, in elderly patients and at the time of disease progression.
authors.affiliation: Department of Oncology, Norwegian Radium Hospital, Oslo University Hospital, PO Box 4953, Nydalen, 0424 Oslo, Norway ; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Ivar
authors.initials: I
authors.lastname: Hompland
authors.affiliation: Department of Oncology, Norwegian Radium Hospital, Oslo University Hospital, PO Box 4953, Nydalen, 0424 Oslo, Norway ; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Øyvind Sverre
authors.initials: ØS
authors.lastname: Bruland
authors.affiliation: Department of Chemistry, Biomedical Center, Analytical Chemistry and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Kumari
authors.initials: K
authors.lastname: Ubhayasekhera
authors.affiliation: Department of Chemistry, Biomedical Center, Analytical Chemistry and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Bergquist
authors.affiliation: Department of Oncology, Norwegian Radium Hospital, Oslo University Hospital, PO Box 4953, Nydalen, 0424 Oslo, Norway ; Department of Tumor Biology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors.forename: Kjetil
authors.initials: K
authors.lastname: Boye
keywords: Drug monitoring; Gastrointestinal stromal tumour; Imatinib; Plasma concentration