(97a) Prediction of Optimal Chemotherapy Dosing Regimens: Balancing Tumor Degradation and Toxicity Effects

During chemotherapy, clinicians must constantly balance the dose of chemotherapeutic agents to reduce the tumor volume and minimize toxicity to the patient. The theory of optimal control can be applied for better assessment of growth-toxicity dynamics and development of drug dosage schedules. The reduction of circulating leukocytes or white blood cells (WBC) by chemotherapeutic agents (myelosuppression) is of primary concern and is often the dose-limiting factor in treatment. For these reasons, the effect of chemotherapy on a patient’s WBC population is considered as a metric of toxicity in the development of optimal dosing regimens. A model is developed to include pharmacokinetic compartments to simulate the concentration of the anticancer agent in distinct parts of the body. Additionally, a more complex model of myelosuppression with demonstrated accuracy is incorporated to analyze the immunotoxic effects. This combined model is evaluated via discretized non-linear programming methods to gain insight into optimal dosage regimens for a specific anticancer agent. This model will aid in quantitating hematological toxicities and will contribute to the design of reliable, personalized tools to optimize chemotherapy and improve patient outcomes.