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Modeling Tumor Growth and Treatment Resistance Dynamics Characterizes Different Response to Gefitinib or Chemotherapy in Non‐Small Cell Lung Cancer

Differences in the effect of gefitinib and chemotherapy on tumor burden in non‐small cell lung cancer remain to be fully understood. Using a Bayesian hierarchical model of tumor size dynamics, we estimated the rates of tumor growth and treatment resistance for patients in the Iressa Pan‐Asia Study s...

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Autores principales: Nagase, Mario, Aksenov, Sergey, Yan, Hong, Dunyak, James, Al‐Huniti, Nidal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080537/
https://www.ncbi.nlm.nih.gov/pubmed/31920008
http://dx.doi.org/10.1002/psp4.12490
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author Nagase, Mario
Aksenov, Sergey
Yan, Hong
Dunyak, James
Al‐Huniti, Nidal
author_facet Nagase, Mario
Aksenov, Sergey
Yan, Hong
Dunyak, James
Al‐Huniti, Nidal
author_sort Nagase, Mario
collection PubMed
description Differences in the effect of gefitinib and chemotherapy on tumor burden in non‐small cell lung cancer remain to be fully understood. Using a Bayesian hierarchical model of tumor size dynamics, we estimated the rates of tumor growth and treatment resistance for patients in the Iressa Pan‐Asia Study study (NCT00322452). The following relationships characterize greater efficacy of gefitinib in epidermal growth factor receptor (EGFR) positive tumors: Maximum drug effect is, in decreasing order, gefitinib in EGFR‐positive, chemotherapy in EGFR‐positive, chemotherapy in EGFR‐negative, and gefitinib in EGFR‐negative tumors; the rate of resistance emergence is, in increasing order: gefitinib in EGFR positive, chemotherapy in EGFR positive, while each is plausibly similar to the rate in EGFR negative tumors, which are estimated with less certainty. The rate of growth is smaller in EGFR‐positive than in EGFR‐negative fully resistant tumors, regardless of treatment. The model can be used to compare treatment effects and resistance dynamics among different drugs.
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spelling pubmed-70805372020-03-19 Modeling Tumor Growth and Treatment Resistance Dynamics Characterizes Different Response to Gefitinib or Chemotherapy in Non‐Small Cell Lung Cancer Nagase, Mario Aksenov, Sergey Yan, Hong Dunyak, James Al‐Huniti, Nidal CPT Pharmacometrics Syst Pharmacol Research Differences in the effect of gefitinib and chemotherapy on tumor burden in non‐small cell lung cancer remain to be fully understood. Using a Bayesian hierarchical model of tumor size dynamics, we estimated the rates of tumor growth and treatment resistance for patients in the Iressa Pan‐Asia Study study (NCT00322452). The following relationships characterize greater efficacy of gefitinib in epidermal growth factor receptor (EGFR) positive tumors: Maximum drug effect is, in decreasing order, gefitinib in EGFR‐positive, chemotherapy in EGFR‐positive, chemotherapy in EGFR‐negative, and gefitinib in EGFR‐negative tumors; the rate of resistance emergence is, in increasing order: gefitinib in EGFR positive, chemotherapy in EGFR positive, while each is plausibly similar to the rate in EGFR negative tumors, which are estimated with less certainty. The rate of growth is smaller in EGFR‐positive than in EGFR‐negative fully resistant tumors, regardless of treatment. The model can be used to compare treatment effects and resistance dynamics among different drugs. John Wiley and Sons Inc. 2020-02-07 2020-03 /pmc/articles/PMC7080537/ /pubmed/31920008 http://dx.doi.org/10.1002/psp4.12490 Text en © 2020 Astra Zeneca. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Research
Nagase, Mario
Aksenov, Sergey
Yan, Hong
Dunyak, James
Al‐Huniti, Nidal
Modeling Tumor Growth and Treatment Resistance Dynamics Characterizes Different Response to Gefitinib or Chemotherapy in Non‐Small Cell Lung Cancer
title Modeling Tumor Growth and Treatment Resistance Dynamics Characterizes Different Response to Gefitinib or Chemotherapy in Non‐Small Cell Lung Cancer
title_full Modeling Tumor Growth and Treatment Resistance Dynamics Characterizes Different Response to Gefitinib or Chemotherapy in Non‐Small Cell Lung Cancer
title_fullStr Modeling Tumor Growth and Treatment Resistance Dynamics Characterizes Different Response to Gefitinib or Chemotherapy in Non‐Small Cell Lung Cancer
title_full_unstemmed Modeling Tumor Growth and Treatment Resistance Dynamics Characterizes Different Response to Gefitinib or Chemotherapy in Non‐Small Cell Lung Cancer
title_short Modeling Tumor Growth and Treatment Resistance Dynamics Characterizes Different Response to Gefitinib or Chemotherapy in Non‐Small Cell Lung Cancer
title_sort modeling tumor growth and treatment resistance dynamics characterizes different response to gefitinib or chemotherapy in non‐small cell lung cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080537/
https://www.ncbi.nlm.nih.gov/pubmed/31920008
http://dx.doi.org/10.1002/psp4.12490
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