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. 2016 Dec 15;6:21.
doi: 10.1186/s13569-016-0062-2. eCollection 2016.

Clinical Implications of Repeated Drug Monitoring of Imatinib in Patients With Metastatic Gastrointestinal Stromal Tumour

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Free PMC article

Clinical Implications of Repeated Drug Monitoring of Imatinib in Patients With Metastatic Gastrointestinal Stromal Tumour

Ivar Hompland et al. Clin Sarcoma Res. .
Free PMC article

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 Cmin plasma concentrations for patients taking <400, 400 and >400 mg daily were 782, 1132 and 1665 ng/mL, respectively (p = 0.010). High IM Cmin levels 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.

Keywords: Drug monitoring; Gastrointestinal stromal tumour; Imatinib; Plasma concentration.

Figures

Fig. 1
Fig. 1
Boxplots showing imatinib mesylate (IM) trough levels (Cmin). Boxes indicate the median, the 25th and 75th percentile, and whiskers represent maximum and minimum values. Outliers are censored. Mean Cmin values ± standard deviations are indicated for each category. a IM Cmin levels categorised according to dose groups: <400 mg (n = 21), 400 mg (n = 69) and >400 mg (n = 6). b IM Cmin levels categorised according to gastric resection (n = 28) or not (n = 41). c IM Cmin levels categorised according to presence (n = 46) or absence (n = 23) of liver metastases. d IM Cmin levels categorised according to whether patients had experienced disease progression or not. For patients with disease progression (right panel), the left box represents the last plasma samples at stable disease and the box to the right represents the plasma samples at the time of progressive disease. For patients with stable disease (left panel), the left box represents the second last plasma samples and the box to the right represent the last plasma samples drawn

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