TY  - JOUR
A1  - Diekstra, Meta H.
A1  - Fritsch, Achim
A1  - Kanefendt, Friederike
A1  - Swen, Jesse Joachim
A1  - Moes, Dirk Jan A. R.
A1  - Sörgel, Fritz
A1  - Kinzig, Martina
A1  - Stelzer, Christoph
A1  - Schindele, Daniel
A1  - Gauler, Thomas
A1  - Hauser, Stefan
A1  - Houtsma, Danny
A1  - Roessler, Max
A1  - Moritz, Berta
A1  - Mross, Klaus
A1  - Bergmann, Lothar
A1  - Oosterwijk, Egbert
A1  - Kiemeney, Lambertus Adrianus
A1  - Guchelaar, Henk-Jan
A1  - Jaehde, Ulrich
T1  - Population modeling integrating pharmacokinetics, pharmacodynamics, pharmacogenetics, and clinical outcome in patients with sunitinib‐treated cancer
T2  - CPT: pharmacometrics & systems pharmacology
N2  - The tyrosine kinase inhibitor sunitinib is used as first‐line therapy in patients with metastasized renal cell carcinoma (mRCC), given in fixed‐dose regimens despite its high variability in pharmacokinetics (PKs). Interindividual variability of drug exposure may be responsible for differences in response. Therefore, dosing strategies based on pharmacokinetic/pharmacodynamic (PK/PD) models may be useful to optimize treatment. Plasma concentrations of sunitinib, its active metabolite SU12662, and the soluble vascular endothelial growth factor receptors sVEGFR‐2 and sVEGFR‐3, were measured in 26 patients with mRCC within the EuroTARGET project and 21 patients with metastasized colorectal cancer (mCRC) from the C‐II‐005 study. Based on these observations, PK/PD models with potential influence of genetic predictors were developed and linked to time‐to‐event (TTE) models. Baseline sVEGFR‐2 levels were associated with clinical outcome in patients with mRCC, whereas active drug PKs seemed to be more predictive in patients with mCRC. The models provide the basis of PK/PD‐guided strategies for the individualization of anti‐angiogenic therapies.
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/46553
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-465539
SN  - 2163-8306
N1  - © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
VL  - 6
IS  - 9
SP  - 604
EP  - 613
PB  - Nature Publ. Group
CY  - London
ER  -