| Autor: |
Ouerdani, A, Struemper, H, Suttle, AB, Ouellet, D, Ribba, B |
| Jazyk: |
angličtina |
| Rok vydání: |
2015 |
| Předmět: |
|
| Zdroj: |
CPT: Pharmacometrics & Systems Pharmacology |
| ISSN: |
2163-8306 |
| Popis: |
The objective was to leverage tumor size data from preclinical experiments to propose a model of tumor growth and angiogenesis inhibition for the analysis of pazopanib efficacy in renal cell carcinoma (RCC) patients. We analyzed tumor data in mice with RCC CAKI-2 cell line treated with pazopanib. Clinical tumor size data obtained in a subset of patients with RCC were also analyzed. A model accounting for the processes of tumor growth, angiogenesis, and drug effect was developed. The final tumor model was composed of two variables: the tumor and its vasculature. Our results show that, both in mice and in humans, pazopanib exhibits a dual mechanism of action, and parameter estimation values highlight the inherent difference between mice and humans on the time scale of tumor size response. We developed a semimechanistic tumor growth inhibition model that takes into account tumor angiogenesis in order to describe the effects of pazopanib in mice. Analyzing rich preclinical data with a semimechanistic model may be a relevant approach to facilitate the description of sparse clinical longitudinal tumor size data and to provide insights for the understanding of the drug mechanisms of action in patients. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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