Severe 5-fluorouracil-induced toxicity due to decreased dihydropyrimidine dehydrogenase activity: report of a patient survival and urinary pyrimidine and dihydropyrimidine levels

Abstract

We report a Japanese woman who survived severe 5-fluorouracil (5-FU) toxicity after receiving 5′-deoxy-5-fluoro-uridine (5′DFUR) for the treatment of breast cancer (pt2n1m1); the toxicity was due to decreased dihydropyrimidine dehydrogenase (DPD) activity. Pharmacokinetic investigation showed very high and prolonged plasma 5-FU concentrations after termination of the oral administration of 5′DFUR. The DPD activity in all plasma samples was below 30 pmol/min per mg protein. Her urinary thymine and uracil levels were high, and the ratios of urinary dihydrothymine/thymine and dihydrouracil/uracil were very low compared with the ratios in healthy people. These findings suggest that determination of urinary pyrimidine and dihydropyrimidine levels would be an appropriate urinary screening sytem that may be useful for evaluating DPD activity before 5-FU treatment is initiated.