Clinical Data Validated Mathematical Model for Intermittent Abiraterone Response in Castration-Resistant Prostate Cancer Patients

Abstract

Over time, tumor treatment resistance inadvertently develops when androgen deprivation therapy (ADT) is applied to metastasized prostate cancer (PCa). To combat tumor resistance, while reducing the harsh side effects o f h ormone t herapy, t he clinician may opt to cyclically alternates the patient’s treatment on and off. This method, known as intermittent ADT, is an alternative to continuous ADT that improves the patient’s quality of life while testosterone levels recover between cycles. In this paper, we explore the response of intermittent ADT to metastasized prostate cancer by em-ploying a previously clinical data validated mathematical model to new clinical data from patients undergoing Abiraterone therapy. This cell quota model, a system of ordinary differential equations constructed using Droop’s nutrient limiting theory, as-sumes the tumor comprises of castration-sensitive (CS) and castration-resistant (CR) cancer sub-populations. The two sub-populations rely on varying levels of intracellular androgen for growth, death and transformation. Due to the complexity of the model, we carry out sensitivity analyses to study the effect o f c ertain p arameters o n their outputs, and to increase the identifiability of each patient’s unique parameter s et. The model’s forecasting results show consistent accuracy for patients with sufficient data, which means the model could give useful information in practice, especially to decide