Optimisation of time-scheduled regimen for anti-cancer drug infusion

Claude Basdevant; Jean Clairambault; Francis Lévi

ESAIM: Mathematical Modelling and Numerical Analysis (2010)

  • Volume: 39, Issue: 6, page 1069-1086
  • ISSN: 0764-583X

Abstract

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The chronotherapy concept takes advantage of the circadian rhythm of cells physiology in maximising a treatment efficacy on its target while minimising its toxicity on healthy organs. The object of the present paper is to investigate mathematically and numerically optimal strategies in cancer chronotherapy. To this end a mathematical model describing the time evolution of efficiency and toxicity of an oxaliplatin anti-tumour treatment has been derived. We then applied an optimal control technique to search for the best drug infusion laws. The mathematical model is a set of six coupled differential equations governing the time evolution of both the tumour cell population (cells of Glasgow osteosarcoma, a mouse tumour) and the mature jejunal enterocyte population, to be shielded from unwanted side effects during a treatment by oxaliplatin. Starting from known tumour and villi populations, and a time dependent free platinum Pt (the active drug) infusion law being given, the mathematical model allows to compute the time evolution of both tumour and villi populations. The tumour population growth is based on Gompertz law and the Pt anti-tumour efficacy takes into account the circadian rhythm. Similarly the enterocyte population is subject to a circadian toxicity rhythm. The model has been derived using, as far as possible, experimental data. We examine two different optimisation problems. The eradication problem consists in finding the drug infusion law able to minimise the number of tumour cells while preserving a minimal level for the villi population. On the other hand, the containment problem searches for a quasi periodic treatment able to maintain the tumour population at the lowest possible level, while preserving the villi cells. The originality of these approaches is that the objective and constraint functions we use are L∞ criteria. We are able to derive their gradients with respect to the infusion rate and then to implement efficient optimisation algorithms.

How to cite

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Basdevant, Claude, Clairambault, Jean, and Lévi, Francis. "Optimisation of time-scheduled regimen for anti-cancer drug infusion." ESAIM: Mathematical Modelling and Numerical Analysis 39.6 (2010): 1069-1086. <http://eudml.org/doc/194297>.

@article{Basdevant2010,
abstract = { The chronotherapy concept takes advantage of the circadian rhythm of cells physiology in maximising a treatment efficacy on its target while minimising its toxicity on healthy organs. The object of the present paper is to investigate mathematically and numerically optimal strategies in cancer chronotherapy. To this end a mathematical model describing the time evolution of efficiency and toxicity of an oxaliplatin anti-tumour treatment has been derived. We then applied an optimal control technique to search for the best drug infusion laws. The mathematical model is a set of six coupled differential equations governing the time evolution of both the tumour cell population (cells of Glasgow osteosarcoma, a mouse tumour) and the mature jejunal enterocyte population, to be shielded from unwanted side effects during a treatment by oxaliplatin. Starting from known tumour and villi populations, and a time dependent free platinum Pt (the active drug) infusion law being given, the mathematical model allows to compute the time evolution of both tumour and villi populations. The tumour population growth is based on Gompertz law and the Pt anti-tumour efficacy takes into account the circadian rhythm. Similarly the enterocyte population is subject to a circadian toxicity rhythm. The model has been derived using, as far as possible, experimental data. We examine two different optimisation problems. The eradication problem consists in finding the drug infusion law able to minimise the number of tumour cells while preserving a minimal level for the villi population. On the other hand, the containment problem searches for a quasi periodic treatment able to maintain the tumour population at the lowest possible level, while preserving the villi cells. The originality of these approaches is that the objective and constraint functions we use are L∞ criteria. We are able to derive their gradients with respect to the infusion rate and then to implement efficient optimisation algorithms. },
author = {Basdevant, Claude, Clairambault, Jean, Lévi, Francis},
journal = {ESAIM: Mathematical Modelling and Numerical Analysis},
keywords = { Dynamical systems; optimisation; circadian rhythms; drugs; therapeutics; cancer.; therapeutics; cancer},
language = {eng},
month = {3},
number = {6},
pages = {1069-1086},
publisher = {EDP Sciences},
title = {Optimisation of time-scheduled regimen for anti-cancer drug infusion},
url = {http://eudml.org/doc/194297},
volume = {39},
year = {2010},
}

TY - JOUR
AU - Basdevant, Claude
AU - Clairambault, Jean
AU - Lévi, Francis
TI - Optimisation of time-scheduled regimen for anti-cancer drug infusion
JO - ESAIM: Mathematical Modelling and Numerical Analysis
DA - 2010/3//
PB - EDP Sciences
VL - 39
IS - 6
SP - 1069
EP - 1086
AB - The chronotherapy concept takes advantage of the circadian rhythm of cells physiology in maximising a treatment efficacy on its target while minimising its toxicity on healthy organs. The object of the present paper is to investigate mathematically and numerically optimal strategies in cancer chronotherapy. To this end a mathematical model describing the time evolution of efficiency and toxicity of an oxaliplatin anti-tumour treatment has been derived. We then applied an optimal control technique to search for the best drug infusion laws. The mathematical model is a set of six coupled differential equations governing the time evolution of both the tumour cell population (cells of Glasgow osteosarcoma, a mouse tumour) and the mature jejunal enterocyte population, to be shielded from unwanted side effects during a treatment by oxaliplatin. Starting from known tumour and villi populations, and a time dependent free platinum Pt (the active drug) infusion law being given, the mathematical model allows to compute the time evolution of both tumour and villi populations. The tumour population growth is based on Gompertz law and the Pt anti-tumour efficacy takes into account the circadian rhythm. Similarly the enterocyte population is subject to a circadian toxicity rhythm. The model has been derived using, as far as possible, experimental data. We examine two different optimisation problems. The eradication problem consists in finding the drug infusion law able to minimise the number of tumour cells while preserving a minimal level for the villi population. On the other hand, the containment problem searches for a quasi periodic treatment able to maintain the tumour population at the lowest possible level, while preserving the villi cells. The originality of these approaches is that the objective and constraint functions we use are L∞ criteria. We are able to derive their gradients with respect to the infusion rate and then to implement efficient optimisation algorithms.
LA - eng
KW - Dynamical systems; optimisation; circadian rhythms; drugs; therapeutics; cancer.; therapeutics; cancer
UR - http://eudml.org/doc/194297
ER -

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