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Integrated Simulation Framework for Toxicity, Dose Intensity, Disease Progression, and Cost Effectiveness for Castration-Resistant Prostate Cancer Treatment With Eribulin
Quantitative model-based analyses are helpful to support decision-making in drug development. In oncology, disease progression/clinical outcome (DPCO) models have been used for early predictions of clinical outcome, but most of such approaches did not include adverse events or dose intensity. In add...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Ltd
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4544051/ https://www.ncbi.nlm.nih.gov/pubmed/26312161 http://dx.doi.org/10.1002/psp4.48 |
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author | van Hasselt, JGC Gupta, A Hussein, Z Beijnen, JH Schellens, JHM Huitema, ADR |
author_facet | van Hasselt, JGC Gupta, A Hussein, Z Beijnen, JH Schellens, JHM Huitema, ADR |
author_sort | van Hasselt, JGC |
collection | PubMed |
description | Quantitative model-based analyses are helpful to support decision-making in drug development. In oncology, disease progression/clinical outcome (DPCO) models have been used for early predictions of clinical outcome, but most of such approaches did not include adverse events or dose intensity. In addition, cost-effectiveness evaluations of investigational compounds are becoming increasingly important. Here, we developed an integrated model-based framework including relevant treatment effects for patients with castration-resistant prostate cancer treated with the anticancer agent eribulin. The framework included (i) a DPCO model relating prostate-specific antigen (PSA) dynamics to survival; (ii) models for adverse events including dose-limiting neutropenia and other graded toxicities; (iii) a model for Eastern Cooperative Oncology Group (ECOG) performance score; (iv) a model for dropout; (v) the consideration of cost effectiveness. The model allowed simulation of realistic treatment courses. Subsequently, simulations evaluating alternative treatment protocols or patient characteristics were performed in order to derive inferences on expected efficacy and cost effectiveness. |
format | Online Article Text |
id | pubmed-4544051 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | John Wiley & Sons, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-45440512015-08-26 Integrated Simulation Framework for Toxicity, Dose Intensity, Disease Progression, and Cost Effectiveness for Castration-Resistant Prostate Cancer Treatment With Eribulin van Hasselt, JGC Gupta, A Hussein, Z Beijnen, JH Schellens, JHM Huitema, ADR CPT Pharmacometrics Syst Pharmacol Original Articles Quantitative model-based analyses are helpful to support decision-making in drug development. In oncology, disease progression/clinical outcome (DPCO) models have been used for early predictions of clinical outcome, but most of such approaches did not include adverse events or dose intensity. In addition, cost-effectiveness evaluations of investigational compounds are becoming increasingly important. Here, we developed an integrated model-based framework including relevant treatment effects for patients with castration-resistant prostate cancer treated with the anticancer agent eribulin. The framework included (i) a DPCO model relating prostate-specific antigen (PSA) dynamics to survival; (ii) models for adverse events including dose-limiting neutropenia and other graded toxicities; (iii) a model for Eastern Cooperative Oncology Group (ECOG) performance score; (iv) a model for dropout; (v) the consideration of cost effectiveness. The model allowed simulation of realistic treatment courses. Subsequently, simulations evaluating alternative treatment protocols or patient characteristics were performed in order to derive inferences on expected efficacy and cost effectiveness. John Wiley & Sons, Ltd 2015-07 2015-06-30 /pmc/articles/PMC4544051/ /pubmed/26312161 http://dx.doi.org/10.1002/psp4.48 Text en © 2015 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics. http://creativecommons.org/licenses/by-nc/4.0/ This is an open access article under the terms of the Creative Commons Attribution-NonCommercial 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 | Original Articles van Hasselt, JGC Gupta, A Hussein, Z Beijnen, JH Schellens, JHM Huitema, ADR Integrated Simulation Framework for Toxicity, Dose Intensity, Disease Progression, and Cost Effectiveness for Castration-Resistant Prostate Cancer Treatment With Eribulin |
title | Integrated Simulation Framework for Toxicity, Dose Intensity, Disease Progression, and Cost Effectiveness for Castration-Resistant Prostate Cancer Treatment With Eribulin |
title_full | Integrated Simulation Framework for Toxicity, Dose Intensity, Disease Progression, and Cost Effectiveness for Castration-Resistant Prostate Cancer Treatment With Eribulin |
title_fullStr | Integrated Simulation Framework for Toxicity, Dose Intensity, Disease Progression, and Cost Effectiveness for Castration-Resistant Prostate Cancer Treatment With Eribulin |
title_full_unstemmed | Integrated Simulation Framework for Toxicity, Dose Intensity, Disease Progression, and Cost Effectiveness for Castration-Resistant Prostate Cancer Treatment With Eribulin |
title_short | Integrated Simulation Framework for Toxicity, Dose Intensity, Disease Progression, and Cost Effectiveness for Castration-Resistant Prostate Cancer Treatment With Eribulin |
title_sort | integrated simulation framework for toxicity, dose intensity, disease progression, and cost effectiveness for castration-resistant prostate cancer treatment with eribulin |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4544051/ https://www.ncbi.nlm.nih.gov/pubmed/26312161 http://dx.doi.org/10.1002/psp4.48 |
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