Pre-treatment serum total bilirubin level as an indicator of optimal CPT-11 dosage.

Background: Irinotecan (CPT-11), a highly effective chemotherapeutic agent, can cause severe neutropenia and diarrhea. The area under the curve of plasma levels over time of SN-38, an active metabolite of CPT-11, was previously reported to correlate with the pre-treatment serum total bilirubin level (PTB). However, there are no established criteria for selecting CPT-11 dose on the basis of PTB.

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

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.

[Combined determination of urine uracil levels and plasma 5-FU clearance for a simple order-made treatment with anticancer agents of FU derivative].

Individual differences exist in the pharmacodynamics of fluorouracil-derived anticancer agents, with circadian variability even in the same patient probably due to individual differences in the distribution of dihydrophrimidine dehydrogenase (DPD), a decomposing enzyme. Though DPD activity is usually determined in the liver or blood, a more simplified estimation of DPD activity has been recently attempted using urine uracil levels. However, because urine uracil level has the drawback of being easily affected by food ingestion or kidney function, in this study it was determined simultaneously with the determination of plasma 5-FU clearance after sustained instillation of 250 mg 5-FU, in order to estimate DPD activity more accurately.