Population Modeling Integrating Pharmacokinetics, Pharmacodynamics, Pharmacogenetics, and Clinical Outcome in Patients With Sunitinib-Treated Cancer

Autor: Diekstra, M.H., Fritsch, A., Kanefendt, F., Swen, J.J., Moes, D.J.A.R., Sorgel, F., Kinzig, M., Stelzer, C., Schindele, D., Gauler, T., Hauser, S., Houtsma, D., Roessler, M., Moritz, B., Mross, K., Bergmann, L., Oosterwijk, E., Kiemeney, L.A., Guchelaar, H.J., Jaehde, U.
Přispěvatelé: MUMC+: DA KFT Medische Staf (9), RS: FHML non-thematic output
Jazyk: angličtina
Rok vydání: 2017
Předmět:
BIOMARKER
Adult
Male
Vascular Endothelial Growth Factor A
ATP Binding Cassette Transporter
Subfamily B
Indoles
Genotype
ACTIVE METABOLITE
SU11248
Medizin
Antineoplastic Agents
METABOLITE SU12662
urologic and male genital diseases
Models
Biological
Polymorphism
Single Nucleotide
RENAL-CELL CARCINOMA
Urological cancers Radboud Institute for Molecular Life Sciences [Radboudumc 15]
Sunitinib
Cytochrome P-450 CYP3A
Humans
Pyrroles
ddc:610
Carcinoma
Renal Cell
Protein Kinase Inhibitors
Aged
Aged
80 and over
Interleukin-8
SINGLE-NUCLEOTIDE POLYMORPHISMS
Original Articles
Middle Aged
Vascular Endothelial Growth Factor Receptor-3
Vascular Endothelial Growth Factor Receptor-2
Kidney Neoplasms
1ST-LINE SUNITINIB
Treatment Outcome
Urological cancers Radboud Institute for Health Sciences [Radboudumc 15]
ENDOTHELIAL GROWTH-FACTOR
Original Article
Female
INTERFERON-ALPHA
Colorectal Neoplasms
HEALTHY-VOLUNTEERS
Zdroj: Cpt Pharmacometrics and Systems Pharmacology, 6, 9, pp. 604-613
CPT: Pharmacometrics and Systems Pharmacology, 6(9), 604-613
Cpt Pharmacometrics and Systems Pharmacology, 6, 604-613
CPT: Pharmacometrics & Systems Pharmacology
CPT: Pharmacometrics and Systems Pharmacology, 6(9), 604-613. Wiley
ISSN: 2163-8306
Popis: Contains fulltext : 177889.pdf (Publisher’s version ) (Open Access) 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.
Databáze: OpenAIRE
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