A Case of Advanced Gastric Cancer Complicated by Severe Toxicity Induced by a Combination of Tegafur, Uracil and Mitomycin C, and Associated with Abnormal Pharmacokinetics

A 60-year-old female patient with gastric cancer and lymph node and liver metastases was treat-ed with a combination of tegafur and uracil (UFT) (375 mg/m2/day) and mitomycin C ( M M Q (5 mg/m2 once weekly). On day 15, when diarrhea appeared, chemotherapy was stopped im-mediately. On day 2 1, the WBC decreased to 900//J and high fever developed. Despite treat-ment with granulocyte colony-stimulating factor and antibiotics, leukopenia persisted and the patient went into septic shock on day 26. On day 34, WBC increased to 5,400//J and she reco-vered, with reduction in the size of the lymph node and liver metastases. Pharmacokinetic ex-amination after intravenous injection of low-dose MMC (0.5 mg/m2) showed a markedly high peak plasma concentration (PPQ, a large area under the time-versus-concentration curve (AUQ and reduced clearance. Similarly, oral administration of UFT (tegafur 300 mg/body) produced a relatively higher PPC and a larger AUC of 5-fluorouracil (FU). The activity of dihydropyrimi-dine dehydrogenase, the rate-limiting enzyme in the metabolism of FU, in peripheral mononuclear cells was within the normal range (0.265 nmol/min/mg). MMC is believed to have played a large part in inducing the severe toxicity observed in this patient. Physicians should be aware of the possibility of severe toxicity during treatment with UFT and MMC, although details of its incidence and mechanism are unclear