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dc.contributor.authorLankheet, NAG
dc.contributor.authorDesar, IME
dc.contributor.authorMulder, SF
dc.contributor.authorBurger, DM
dc.contributor.authorKweekel, DM
dc.contributor.authorvan Herpen, CML
dc.contributor.authorvan der Graaf, WTA
dc.contributor.authorvan Erp, NP
dc.date.accessioned2018-02-19T09:47:53Z
dc.date.issued2017-10
dc.identifier.citationBritish journal of clinical pharmacology, 2017, 83 (10), pp. 2195 - 2204
dc.identifier.issn0306-5251
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1237
dc.identifier.eissn1365-2125
dc.identifier.doi10.1111/bcp.13327
dc.description.abstractAim 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.
dc.formatPrint-Electronic
dc.format.extent2195 - 2204
dc.languageeng
dc.language.isoeng
dc.subjectHumans
dc.subjectNeoplasms
dc.subjectSulfonamides
dc.subjectPyrimidines
dc.subjectPyrroles
dc.subjectIndoles
dc.subjectAntineoplastic Agents
dc.subjectProtein Kinase Inhibitors
dc.subjectDrug Monitoring
dc.subjectTreatment Outcome
dc.subjectChromatography, High Pressure Liquid
dc.subjectRetrospective Studies
dc.subjectFeasibility Studies
dc.subjectAdolescent
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectChild
dc.subjectFemale
dc.subjectMale
dc.subjectTandem Mass Spectrometry
dc.subjectYoung Adult
dc.subjectImatinib Mesylate
dc.subjectSunitinib
dc.titleOptimizing the dose in cancer patients treated with imatinib, sunitinib and pazopanib.
dc.typeJournal Article
dcterms.dateAccepted2017-05-10
rioxxterms.versionofrecord10.1111/bcp.13327
rioxxterms.licenseref.startdate2017-10
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfBritish journal of clinical pharmacology
pubs.issue10
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical and Translational Sarcoma
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical and Translational Sarcoma
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume83
pubs.embargo.termsNot known
icr.researchteamClinical and Translational Sarcomaen_US
dc.contributor.icrauthorvan der Graaf, Wilhelminaen
dc.contributor.icrauthorMarsden,en


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