s-1-(combination) and Dihydropyrimidine-Dehydrogenase-Deficiency

Topics: Antineoplastic Agents; Dihydropyrimidine Dehydrogenase Deficiency; Dihydrouracil Dehydrogenase (NADP); Drug Combinations; Fluorouracil; Genotype; Humans; Neoplasms; Oxonic Acid; Pharmacogenomic Testing; Phenotype; Point-of-Care Testing; Pyrrolidines; Tegafur; Thymine; Trifluridine; Uracil

The patient was a 70-year-old woman, who had undergone total gastrectomy and splenectomy with D2 lymph node dissection, for stage II gastric cancer. We admitted S-1 of 80 mg/day in adjuvant chemotherapy on postoperative day 28. There were no adverse events for one week, and she was discharged. Severe diarrhea occurred 6 days following discharge, but she continued to take S-1. Two weeks after discharge, she visited our hospital, suffering from severe dehydration (grade 4), leucopenia (grade 4)and thrombocytopenia (grade 3). Unfortunately, she died of lung edema and multiple organ failure 28 days after chemotherapy. We measured the mRNA expression level of dihydropyrimidine dehydrogenase (DPD) of the patient's liver by the Dannenberg Tumor Profile method. The expression level of DPD was significantly low, so we suggested that the severe bone marrow suppression might have been caused by the disordered metabolism of 5-FU.

Topics: Aged; Antimetabolites, Antineoplastic; Bone Marrow; Chemotherapy, Adjuvant; Dihydropyrimidine Dehydrogenase Deficiency; Drug Combinations; Female; Gastrectomy; Humans; Liver; Lymph Node Excision; Oxonic Acid; Splenectomy; Stomach Neoplasms; Tegafur

Dihydropyrimidine dehydrogenase (DPD) is a reducing enzyme for fluoropyrimidine which is a widely-used anti-cancer agent, and its deficiency leads to serious toxicities. We report a rare patient with a DPD deficiency. A 39-year-old man was suspected to have a gastric cancer recurrence from the elevation of CEA. Although TS-1 was administered for five days, it was stopped due to the development of grade 2 anorexia and nausea. Although we administered UFT at his request after a one-month drug rest, grade 1 stomatorrhagia besides the former adverse events developed after five days. Therefore he discontinued it and was admitted to our hospital. After 19 days, he died from multiple brain hemorrhage despite the intensive therapies. We considered that the congenital DPD deficiency caused the development of these adverse events because the DPD value was less than 5 pmol/mg/min in mononuclear cells of peripheral blood.

Topics: Adult; Anorexia; Antimetabolites, Antineoplastic; Bone Neoplasms; Cerebral Hemorrhage; Dihydropyrimidine Dehydrogenase Deficiency; Drug Combinations; Fatal Outcome; Humans; Liver Neoplasms; Male; Nausea; Oxonic Acid; Stomach Neoplasms; Tegafur; Uracil