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Chemotherapy-Induced Cachexia and Model-Informed Dosing to Preserve Lean Mass in Cancer Treatment

View ORCID ProfileSuzan Farhang-Sardroodi, Michael A. La Croix, View ORCID ProfileKathleen P. Wilkie
doi: https://doi.org/10.1101/2021.10.01.462698
Suzan Farhang-Sardroodi
1Modelling Infection and Immunity Lab, Mathematics Statistics, York University, Toronto, ON, Canada
2Centre for Disease Modelling (CDM), Mathematics Statistics, York University, Toronto, ON, Canada
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Michael A. La Croix
3Department of Mathematics, Ryerson University, Toronto, ON, Canada
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Kathleen P. Wilkie
3Department of Mathematics, Ryerson University, Toronto, ON, Canada
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  • For correspondence: kpwilkie@ryerson.ca
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Abstract

Although chemotherapy is a standard treatment for cancer, it comes with significant side effects. In particular, certain agents can induce severe muscle loss, known as cachexia, worsening patient quality of life and treatment outcomes. 5-fluorouracil, an anti-cancer agent used to treat several cancers, has been shown to cause muscle loss. Experimental data indicates a non-linear dose-dependence for muscle loss in mice treated with daily or week-day schedules. We present a mathematical model of chemotherapy-induced muscle wasting that captures this non-linear dose-dependence. Area-under-the-curve metrics are proposed to quantify the treatment’s effects on lean mass and tumour control. Model simulations are used to explore alternate dosing schedules, aging effects, and morphine use in chemotherapy treatment with the aim of better protecting lean mass while actively targeting the tumour, ultimately leading to improved personalization of treatment planning and improved patient quality of life.

Author Summary In this paper we present a novel mathematical model for muscle loss due to cancer chemotherapy treatment. Loss of muscle mass relates to increased drug toxicity and side-effects, and to decreased patient quality of life and survival rates. With our model, we examine the therapeutic efficacy of various dosing schedules with the aim of controlling a growing tumour while also preserving lean mass. Preservation of body composition, in addition to consideration of inflammation and immune interactions, the gut microbiome, and other systemic health measures, may lead to improved patient-specific treatment plans that improve patient quality of life.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted October 01, 2021.
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Chemotherapy-Induced Cachexia and Model-Informed Dosing to Preserve Lean Mass in Cancer Treatment
Suzan Farhang-Sardroodi, Michael A. La Croix, Kathleen P. Wilkie
bioRxiv 2021.10.01.462698; doi: https://doi.org/10.1101/2021.10.01.462698
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Chemotherapy-Induced Cachexia and Model-Informed Dosing to Preserve Lean Mass in Cancer Treatment
Suzan Farhang-Sardroodi, Michael A. La Croix, Kathleen P. Wilkie
bioRxiv 2021.10.01.462698; doi: https://doi.org/10.1101/2021.10.01.462698

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