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A Population Dynamic Energy Budget-Based Tumor Growth Inhibition Model for Etoposide Effects on Wistar Rats
E M Tosca1, M C Pigatto2,3, T Dalla Costa2
1Dipartimento di Ingegneria Industriale e dell'Informazione, Universita degli Studi di Pavia, I-27100, Pavia, Italy.
Pharmaceutical Research
|January 13, 2019
Summary
A new Dynamic Energy Budget (DEB)-based tumor-in-host growth inhibition (TGI) model effectively describes etoposide
Area of Science:
- Pharmacology and Toxicology
- Mathematical Modeling
- Cancer Research
Background:
- Etoposide is a chemotherapy drug used to treat various cancers.
- Understanding drug effects on both tumor and host is crucial for effective treatment.
- Walker-256 tumor in rats is a model for studying tumor growth and associated cachexia.
Purpose of the Study:
- To develop a population pharmacokinetic/pharmacodynamic (PK/PD) tumor-in-host model.
- To describe etoposide's effects on tumor cells and the host in Walker-256 tumor-bearing rats.
- To validate the Dynamic Energy Budget (DEB)-based tumor-in-host growth inhibition (TGI) model in rats.
Main Methods:
- Etoposide treatment in Wistar rats (tumor-free and tumor-bearing).
- Development of a DEB-based TGI model to analyze experimental data.
- Assessment of plasma and intratumoral etoposide concentrations as drivers of tumor kinetics.
Main Results:
- The model simultaneously describes tumor and host growth dynamics.
- It captures etoposide's antitumor effects and drug-induced cachexia.
- Schedule-dependent inhibition of etoposide was observed, driven by intratumoral drug concentration.
Conclusions:
- The DEB-based TGI model's capabilities are confirmed in rats, previously shown in mice.
- Mechanistic modeling combined with well-designed experiments aids understanding of in vivo tumor growth and drug effects.
- This approach is valuable for optimizing cancer treatment strategies.
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