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A Pharmacometric Fr...
A Pharmacometric Framework for Axitinib Exposure, Efficacy, and Safety in Metastatic Renal Cell Carcinoma Patients
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- Schindler, Emilie (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Pharmacometrics group
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Amantea, Michael A (författare)
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- Karlsson, Mats O (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Pharmacometrics group
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- Friberg, Lena E (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Pharmacometrics group
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(creator_code:org_t)
- 2017-05-26
- 2017
- Engelska.
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Ingår i: CPT. - : Wiley. - 2163-8306. ; 6:6, s. 373-382
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- The relationships between exposure, biomarkers (vascular endothelial growth factor (VEGF), soluble VEGF receptors (sVEGFR)-1, -2, -3, and soluble stem cell factor receptor (sKIT)), tumor sum of longest diameters (SLD), diastolic blood pressure (dBP), and overall survival (OS) were investigated in a modeling framework. The dataset included 64 metastatic renal cell carcinoma patients (mRCC) treated with oral axitinib. Biomarker timecourses were described by indirect response (IDR) models where axitinib inhibits sVEGFR-1, -2, and -3 production, and VEGF degradation. No effect was identified on sKIT. A tumor model using sVEGFR-3 dynamics as driver predicted SLD data well. An IDR model, with axitinib exposure stimulating the response, characterized dBP increase. In a time-to-event model the SLD timecourse predicted OS better than exposure, biomarker- or dBP-related metrics. This type of framework can be used to relate pharmacokinetics, efficacy, and safety to long-term clinical outcome in mRCC patients treated with VEGFR inhibitors.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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