Pharmacodynamic modeling of adverse effects of anti-cancer drug treatment

Abstract

PURPOSE: Adverse effects related to anti-cancer drug treatment influence patient's quality of life, have an impact on the realized dosing regimen, and can hamper response to treatment. Quantitative models that relate drug exposure to the dynamics of adverse effects have been developed and proven to be very instrumental to optimize dosing schedules. The aims of this review were (i) to provide a perspective of how adverse effects of anti-cancer drugs are modeled and (ii) to report several model structures of adverse effect models that describe relationships between drug concentrations and toxicities. METHODS: Various quantitative pharmacodynamic models that model adverse effects of anti-cancer drug treatment were reviewed. RESULTS: Quantitative models describing relationships between drug exposure and myelosuppression, cardiotoxicity, and graded adverse effects like fatigue, hand-foot syndrome (HFS), rash, and diarrhea have been presented for different anti-cancer agents, including their clinical applicability. CONCLUSIONS: Mathematical modeling of adverse effects proved to be a helpful tool to improve clinical management and support decision-making (especially in establishment of the optimal dosing regimen) in drug development. The reported models can be used as templates for modeling a variety of anti-cancer-induced adverse effects to further optimize therapy.