Publication year
2017Source
British Journal of Clinical Pharmacology, 83, 10, (2017), pp. 2195-2204ISSN
Publication type
Article / Letter to editor

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Organization
Clinical Pharmacy
Medical Oncology
Journal title
British Journal of Clinical Pharmacology
Volume
vol. 83
Issue
iss. 10
Page start
p. 2195
Page end
p. 2204
Subject
Radboudumc 0: Other Research RIHS: Radboud Institute for Health Sciences; Radboudumc 15: Urological cancers RIHS: Radboud Institute for Health Sciences; Radboudumc 4: lnfectious Diseases and Global Health RIHS: Radboud Institute for Health Sciences; Radboudumc 9: Rare cancers RIHS: Radboud Institute for Health SciencesAbstract
AIM: Fixed dose oral tyrosine kinase inhibitors imatinib, sunitinib and pazopanib show a high interpatient variability in plasma exposure. A relationship between plasma exposure and treatment outcome has been established, which supports the rationale for dose optimization of these drugs. The aim of this study was to monitor how many patients reached adequate trough levels after therapeutic drug monitoring-based dose optimization in daily practice. METHODS: A cohort study was performed in patients treated with imatinib, sunitinib or pazopanib of whom follow-up drug levels were measured between August 2012 and April 2016. Patients' characteristics were collected by reviewing electronic patient records. Drug levels were measured using high-performance liquid chromatography coupled with tandem mass spectrometry and trough levels were estimated using a predefined algorithm. Dose interventions were proposed based on trough levels. RESULTS: In total, 396 trough levels were determined in 109 patients. Median sample frequency per patient was 3. During the first measurement only 38% of patients showed trough levels within the predefined target ranges despite standard dosing; 52% of the patients showed drug levels below and 10% above the target range. In 35 out of 41 patients (85%) dose interventions led to adequate trough levels. Eventually, 64% of the total cohort reached adequate trough levels. CONCLUSIONS: Dose optimization proved an effective tool to reach adequate trough levels in patients treated with imatinib, sunitinib and pazopanib. The percentage of patients with adequate trough levels increased from 38 to 64%. Therapeutic drug monitoring may add to the improvement of efficacy and reduction of toxicity and costs of these treatments.
This item appears in the following Collection(s)
- Academic publications [202802]
- Faculty of Medical Sciences [80020]
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