Optimizing the dose in cancer patients treated with imatinib, sunitinib and pazopanib.

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Date
2017-10Author
Lankheet, NAG
Desar, IME
Mulder, SF
Burger, DM
Kweekel, DM
van Herpen, CML
van der Graaf, WTA
van Erp, NP
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Subject
Humans
Neoplasms
Sulfonamides
Pyrimidines
Pyrroles
Indoles
Antineoplastic Agents
Protein Kinase Inhibitors
Drug Monitoring
Treatment Outcome
Chromatography, High Pressure Liquid
Retrospective Studies
Feasibility Studies
Adolescent
Adult
Aged
Aged, 80 and over
Middle Aged
Child
Female
Male
Tandem Mass Spectrometry
Young Adult
Imatinib Mesylate
Sunitinib
Research team
Clinical and Translational Sarcoma
Language
eng
Date accepted
2017-05-10
License start date
2017-10
Citation
British journal of clinical pharmacology, 2017, 83 (10), pp. 2195 - 2204