Unpredicted severe toxicity after 5-fluorouracil treatment due to dihydropyrimidine dehydrogenase deficiency.
Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the catabolism of 5-fluorouracil (5-FU). Thus, patients with a DPD deficiency are at risk of developing severe 5-FU-associated toxicity. A 37-year-old female with gastric cancer underwent a curative operation, followed by adjuvant chemotherapy consisting of 5-FU and epirubicin. After the first cycle of chemotherapy, the patient manifested grade 2 mucositis and febrile neutropenia, and when her treatment was subsequently continued with doxifluridine she developed severe mucositis and febrile neutropenia. A PCR study revealed that her DPD mRNA level was lower than that in a control group. Thus, when considering the routine use of 5-FU for the treatment of cancer patients, an analysis of DPD activity or screening for DPD mutations is warranted in confined patients who experience unpredicted severe toxicity after initial 5-FU administration, even though DPD deficiency is a rare metabolic defect.
Baek
Jin Ho
JH
Department of Hematology/Oncology, Kyungpook National University Hospital, Daegu, Korea.
Kim
Jong Gwang
JG
Kim
Shi Nae
SN
Kim
Dong Hwan
DH
Sohn
Sang Kyun
SK
Hong
Young Jun
YJ
Lee
Kyu Bo
KB
D000230:Adenocarcinoma / Q000150:complications / Q000188:drug therapy* / Q000601:surgery; D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D017024:Chemotherapy, Adjuvant; D054067:Dihydropyrimidine Dehydrogenase Deficiency; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects*; D006801:Humans; D018570:Risk Assessment; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000601:surgery
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil