Severe 5-fluorouracil-related toxicity in a Japanese patient with dihydropyrimidine dehydrogenase deficiency

Abstract

Dihydropyrimidine dehydrogenase (DPD) is the major enzyme involved in the catabolism of pyrimidines and fluoropyrimidines. Severe 5-fluorouracil (5-FU) toxicity has been reported in patients with DPD deficiency in Western countries. We now report a case of 5-FU-related severe toxicity in a Japanese patient with DPD deficiency. A-44 year-old woman with gastric cancer associated with peritoneal dissemination underwent palliative gastrectomy at the Tochigi Cancer Center. After surgery, she was treated with a combination of mitomycin C (12.5 mg/m2, bolus iv) and 5-FU (312.5 mg/m2 per day, continuous infusion). Eight days after commencement, the chemotherapy was discontinued because of severe gastrointestinal toxicity. On day 12 the patient developed a high fever with granulocytopenia (617.4 granulocytes/μl). DPD-activity in peripheral blood mononuclear cells (PBMC) was extremely low (up to 8.9 pmol/mg protein per min) and serum and urine uracil concentrations were high, at 225.2 ng/ml and 2334.2 ng/mg creatinine, respectively. To our knowledge, this appears to be the first case of 5-FU-related severe toxicity due to DPD deficiency reported in a Japanese patient.