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dc.contributor.authorLankheet, NAGen_US
dc.contributor.authorDesar, IMEen_US
dc.contributor.authorMulder, SFen_US
dc.contributor.authorBurger, DMen_US
dc.contributor.authorKweekel, DMen_US
dc.contributor.authorvan Herpen, CMLen_US
dc.contributor.authorvan der Graaf, WTAen_US
dc.contributor.authorvan Erp, NPen_US
dc.coverage.spatialEnglanden_US
dc.date.accessioned2018-02-19T09:47:53Z
dc.date.issued2017-10en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/28500677en_US
dc.identifier.citationBr J Clin Pharmacol, 2017, 83 (10), pp. 2195 - 2204en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1237
dc.identifier.eissn1365-2125en_US
dc.identifier.doi10.1111/bcp.13327en_US
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.en_US
dc.format.extent2195 - 2204en_US
dc.languageengen_US
dc.language.isoengen_US
dc.subjectimatiniben_US
dc.subjectindividualized dosingen_US
dc.subjectpazopaniben_US
dc.subjectpharmacokineticsen_US
dc.subjectsunitiniben_US
dc.subjecttherapeutic drug monitoringen_US
dc.subjectAdolescenten_US
dc.subjectAdulten_US
dc.subjectAgeden_US
dc.subjectAged, 80 and overen_US
dc.subjectAntineoplastic Agentsen_US
dc.subjectChilden_US
dc.subjectChromatography, High Pressure Liquiden_US
dc.subjectDrug Monitoringen_US
dc.subjectFeasibility Studiesen_US
dc.subjectFemaleen_US
dc.subjectHumansen_US
dc.subjectImatinib Mesylateen_US
dc.subjectIndolesen_US
dc.subjectMaleen_US
dc.subjectMiddle Ageden_US
dc.subjectNeoplasmsen_US
dc.subjectProtein Kinase Inhibitorsen_US
dc.subjectPyrimidinesen_US
dc.subjectPyrrolesen_US
dc.subjectRetrospective Studiesen_US
dc.subjectSulfonamidesen_US
dc.subjectSunitiniben_US
dc.subjectTandem Mass Spectrometryen_US
dc.subjectTreatment Outcomeen_US
dc.subjectYoung Adulten_US
dc.titleOptimizing the dose in cancer patients treated with imatinib, sunitinib and pazopanib.en_US
dc.typeJournal Article
dcterms.dateAccepted2017-05-10en_US
rioxxterms.versionofrecord10.1111/bcp.13327en_US
rioxxterms.licenseref.startdate2017-10en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfBr J Clin Pharmacolen_US
pubs.issue10en_US
pubs.notesNot knownen_US
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-statusPublisheden_US
pubs.volume83en_US
pubs.embargo.termsNot knownen_US
icr.researchteamClinical and Translational Sarcomaen_US
dc.contributor.icrauthorvan der Graaf, Wilhelminaen_US
dc.contributor.icrauthorMarsden,en_US


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