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

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.

A practical guide for the generation of model-based virtual clinical trials

“…Historically, sensitivity analyses were conducted after the system reached a steady state; however, now it is common practice to choose a meaningful timepoint, such as immediately following a treatment administration to assess parameter sensitivity. One can extend this analysis to a dynamic sensitivity, by computing S i (t) for 0 ≤ t ≤ t final , to explore the robustness of parameters over a timeframe of interest (Farhang-Sardroodi et al, 2022).…”