Mathematical Modelling of Growth Kinetics of Walker 256 Carcinoma in Rats

Dagnino, G.; Rocchetti, Maurizio; Urso, R.; Guaitani, A.; Bartošek, I.

doi:10.1159/000225712

Cited by 2 publications

(2 citation statements)

References 11 publications

(14 reference statements)

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“…5). It is also interesting to notice that, in its first implementation (15), the model of unperturbed growth was successfully used for modeling the tumor growth curves in rats. This flexibility is particularly important for accommodating the var- In the left panel, the parameters refer to the fitting of controls and animals treated every day for 11 days (qd ϫ 11) from Day 9.…”

Section: Discussionmentioning

confidence: 99%

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Predictive Pharmacokinetic-Pharmacodynamic Modeling of Tumor Growth Kinetics in Xenograft Models after Administration of Anticancer Agents

et al. 2004

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The available mathematical models describing tumor growth and the effect of anticancer treatments on tumors in animals are of limited use within the drug industry. A simple and effective model would allow applying quantitative thinking to the preclinical development of oncology drugs. In this article, a minimal pharmacokinetic-pharmacodynamic model is presented, based on a system of ordinary differential equations that link the dosing regimen of a compound to the tumor growth in animal models. The growth of tumors in nontreated animals is described by an exponential growth followed by a linear growth. In treated animals, the tumor growth rate is decreased by a factor proportional to both drug concentration and number of proliferating tumor cells. A transit compartmental system is used to model the process of cell death, which occurs at later times. The parameters of the pharmacodynamic model are related to the growth characteristics of the tumor, to the drug potency, and to the kinetics of the tumor cell death. Therefore, such parameters can be used for ranking compounds based on their potency and for evaluating potential differences in the tumor cell death process. The model was extensively tested on discovery candidates and known anticancer drugs. It fitted well the experimental data, providing reliable parameter estimates. On the basis of the parameters estimated in a first experiment, the model successfully predicted the response of tumors exposed to drugs given at different dose levels and/or schedules. It is, thus, possible to use the model prospectively, optimizing the design of new experiments.

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Section: Discussionmentioning

confidence: 99%

“…B and Eq. C adequately describes the tumor growth in control animals (15). However, for computational reasons, it is convenient to use a single differentiable function, especially in view of the subsequent introduction of the effect of an anticancer agent (see "Perturbed Growth Model"):…”

Section: Pharmacodynamic Modelmentioning

confidence: 99%