Population modeling integrating pharmacokinetics, pharmacodynamics, pharmacogenetics, and clinical outcome in patients with sunitinib-treated cancer

M. H. Diekstra, A. Fritsch, F. Kanefendt, J. J. Swen, Moes Djar, F. Sörgel, M. Kinzig, C. Stelzer, D. Schindele, T. Gauler, S. Hauser, D. Houtsma, M. Roessler, B. Moritz, K. Mross, L. Bergmann, E. Oosterwijk, L. A. Kiemeney, H. J. Guchelaar, U. Jaehde

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

17 Citaten (Scopus)

Samenvatting

The tyrosine kinase inhibitor sunitinib is used as first-line therapy in patients with metastasized renal cell carcinoma (mRC given in fixed-dose regimens despite its high variability in pharmacokinetics (PKs). Interindividual variability of drug expos may be responsible for differences in response. Therefore, dosing strategies based on pharmacokinetic/pharmacodyna (PK/PD) models may be useful to optimize treatment. Plasma concentrations of sunitinib, its active metabolite SU12662, a the soluble vascular endothelial growth factor receptors sVEGFR-2 and sVEGFR-3, were measured in 26 patients with mR within the EuroTARGET project and 21 patients with metastasized colorectal cancer (mCRC) from the C-II-005 study. Based these observations, PK/PD models with potential influence of genetic predictors were developed and linked to time-to-ev (TTE) models. Baseline sVEGFR-2 levels were associated with clinical outcome in patients with mRCC, whereas active d PKs seemed to be more predictive in patients with mCRC. The models provide the basis of PK/PD-guided strategies for individualization of anti-angiogenic therapies.

Originele taal-2Engels
Pagina's (van-tot)604-613
Aantal pagina's10
TijdschriftCPT: Pharmacometrics and Systems Pharmacology
Volume6
Nummer van het tijdschrift9
DOI's
StatusGepubliceerd - sep. 2017
Extern gepubliceerdJa

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