Support of TS-1, 5-FU preparation containing potent DPD inhibitor by determination of urinary uracil/serum 5-FU clearance

摘要

Though FU-derived anticancer agents are metabolized and detoxicated by dihydropyrimidine dehydrogenase (DPD), its wide distribution of activity is concerned primarily in the antitumor effects or side effects of 5-FU. In recent years, it has become possible to predict the metabolism of FU-derived anticancer agents by DPD activity through the determination of urinary uracil levels. In the present study, therefore, we examined whether or not urinary uracil levels could be used as a predictor for as certaining the efficacy and/or side effects of TS-1, which contains a potent DPD inhibitor. Consequently, the following relationship was revealed to exist between urinary uracil levels and clinical effects of TS-1: 1) The effect of TS-1 administration was generally good in patients whose uracil level was within the standard values with no presentation of serious side effects. 2) The administration of TS-1 was also useful even in patients whose uracil levels were below the standard value. 3) Though no side effects were observed when a conventional FU-derived anticancer agent was administered to patients showing an urinary uracil level below the standard value, some side effects appeared when TS-1 was administered. Under present circumstances where understanding of genome diagnosis and establishment of informed consent are rather difficult, this approach of predicting DPD activities through the determination of urinary uracil levels seems to be of help for deciding a therapeutic regimen based on the patient's constitutional features when a cancer chemotherapy with TS-1 is performed.