Biomarker- versus drug-driven tumor growth inhibition models: an equivalence analysis

Verfasser / Beitragende:
[Maria Sardu, Italo Poggesi, Giuseppe De Nicolao]
Ort, Verlag, Jahr:
2015
Enthalten in:
Journal of Pharmacokinetics and Pharmacodynamics, 42/6(2015-12-01), 611-626
Format:
Artikel (online)
ID: 605533776
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024 7 0 |a 10.1007/s10928-015-9427-z  |2 doi 
035 |a (NATIONALLICENCE)springer-10.1007/s10928-015-9427-z 
245 0 0 |a Biomarker- versus drug-driven tumor growth inhibition models: an equivalence analysis  |h [Elektronische Daten]  |c [Maria Sardu, Italo Poggesi, Giuseppe De Nicolao] 
520 3 |a The mathematical modeling of tumor xenograft experiments following the dosing of antitumor drugs has received much attention in the last decade. Biomarker data can further provide useful insights on the pathological processes and be used for translational purposes in the early clinical development. Therefore, it is of particular interest the development of integrated pharmacokinetic-pharmacodynamic (PK-PD) models encompassing drug, biomarker and tumor-size data. This paper investigates the reciprocal consistency of three types of models: drug-to-tumor, such as established drug-driven tumor growth inhibition (TGI) models, drug-to-biomarker, e.g. indirect response models, and biomarker-to-tumor, e.g. the more recent biomarker-driven TGI models. In particular, this paper derives a mathematical relationship that guarantees the steady-state equivalence of the cascade of drug-to-biomarker and biomarker-to-tumor models with a drug-to-tumor TGI model. Using the Simeoni TGI model as a reference, conditions for steady-state equivalence are worked out and used to derive a new biomarker-driven model. Simulated and real data are used to show that in realistic cases the steady-state equivalence extends also to transient responses. The possibility of predicting the drug-to-tumor potency of a new candidate drug based only on biomarker response is discussed. 
540 |a Springer Science+Business Media New York, 2015 
690 7 |a PK-PD models  |2 nationallicence 
690 7 |a Causal pathways  |2 nationallicence 
690 7 |a Biomarkers  |2 nationallicence 
690 7 |a Tumor growth inhibition  |2 nationallicence 
690 7 |a Xenograft experiments  |2 nationallicence 
690 7 |a Simeoni model  |2 nationallicence 
700 1 |a Sardu  |D Maria  |u Dipartimento di Ingegneria Industriale e dell'Informazione, Università di Pavia, Via Ferrata 1, 27100, Pavia, Italy  |4 aut 
700 1 |a Poggesi  |D Italo  |u Clinical Pharmacology & Pharmacometrics, Janssen Research & Development, 2340, Beerse, Belgium  |4 aut 
700 1 |a De Nicolao  |D Giuseppe  |u Dipartimento di Ingegneria Industriale e dell'Informazione, Università di Pavia, Via Ferrata 1, 27100, Pavia, Italy  |4 aut 
773 0 |t Journal of Pharmacokinetics and Pharmacodynamics  |d Springer US; http://www.springer-ny.com  |g 42/6(2015-12-01), 611-626  |x 1567-567X  |q 42:6<611  |1 2015  |2 42  |o 10928 
856 4 0 |u https://doi.org/10.1007/s10928-015-9427-z  |q text/html  |z Onlinezugriff via DOI 
898 |a BK010053  |b XK010053  |c XK010000 
900 7 |a Metadata rights reserved  |b Springer special CC-BY-NC licence  |2 nationallicence 
908 |D 1  |a research-article  |2 jats 
949 |B NATIONALLICENCE  |F NATIONALLICENCE  |b NL-springer 
950 |B NATIONALLICENCE  |P 856  |E 40  |u https://doi.org/10.1007/s10928-015-9427-z  |q text/html  |z Onlinezugriff via DOI 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Sardu  |D Maria  |u Dipartimento di Ingegneria Industriale e dell'Informazione, Università di Pavia, Via Ferrata 1, 27100, Pavia, Italy  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Poggesi  |D Italo  |u Clinical Pharmacology & Pharmacometrics, Janssen Research & Development, 2340, Beerse, Belgium  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a De Nicolao  |D Giuseppe  |u Dipartimento di Ingegneria Industriale e dell'Informazione, Università di Pavia, Via Ferrata 1, 27100, Pavia, Italy  |4 aut 
950 |B NATIONALLICENCE  |P 773  |E 0-  |t Journal of Pharmacokinetics and Pharmacodynamics  |d Springer US; http://www.springer-ny.com  |g 42/6(2015-12-01), 611-626  |x 1567-567X  |q 42:6<611  |1 2015  |2 42  |o 10928