RT Journal Article
SR Electronic
T1 Application of Pharmacometrics of 5-Fluorouracil to Personalized Medicine: A Tool for Predicting Pharmacokinetic–Pharmacodynamic/Toxicodynamic Responses
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 6585
OP 6597
DO 10.21873/anticanres.14683
VO 40
IS 12
A1 SHINJI KOBUCHI
A1 YUKAKO ITO
YR 2020
UL http://ar.iiarjournals.org/content/40/12/6585.abstract
AB Recently, therapeutic drug monitoring of 5-fluorouracil (5-FU), the key chemotherapeutic drug for colorectal cancer, has been applied in daily clinical practice and has contributed towards improving clinical outcomes. However, current dose modifications are based only on values of the area under the plasma concentration–time profile, which are simply calculated from plasma 5-FU concentrations and infusion periods. When dose-limiting toxicities occur, the dosing is empirically reduced or discontinued, leading to treatment failure. To prevent this predictable failure and obtain better clinical outcomes, rational dosage-based strategies are required for 5-FU. Combining therapeutic drug monitoring with a mathematical approach using a pharmacokinetic– pharmacodynamic/toxicodynamic model is expected to help simulate time-course profiles of the efficacy of drugs and the degree of toxicity, thereby contributing towards dose setting for individual patients. Therefore, to facilitate pharmacometric modelling and simulation techniques for optimising current oncology therapies, this review focuses on pharmacometrics approaches for personalizing 5-FU-based chemotherapy.