Dihydropyrimidine dehydrogenase deficiency: a pharmacogenetic defect causing severe adverse reactions to 5-fluorouracil-based chemotherapy.
OBJECTIVE
To describe the pharmacogenetic syndrome of dihydropyrimidine dehydrogenase (DPD) deficiency, which predisposes patients with cancer to potentially lethal adverse reactions following 5-fluorouracil (5-FU)-based chemotherapy.


METHODS
Published articles, abstracts, and conference proceedings.


RESULTS
Genetic deficiencies in DPD, the rate-limiting enzyme responsible for 5-FU catabolism, may occur in 3% or more of patients with cancer putting them at increased risk for unusually severe adverse reactions (e.g., diarrhea, stomatitis, mucositis, myelosuppression, neurotoxicity) to standard doses of 5-FU. Diagnosis of DPD deficiency must be confirmed by specialized laboratory tests. The principle treatment for DPD-deficient patients with severe acute 5-FU reactions is supportive care; however, the administration of thymidine potentially may reverse severe 5-FU-induced neurologic symptoms such as encephalopathy and coma.


CONCLUSIONS
Early recognition of this serious pharmacogenetic syndrome may allow for the modification of future chemotherapy, thus avoiding further life-threatening toxicities.


CONCLUSIONS
Nurses must understand the pharmacology, mechanism of action, clinical presentation, potentially lethal risks, and traumatic psychosocial stresses experienced by DPD-deficient patients with cancer receiving 5-FU therapy in order to develop timely interventions and alternative plans of care.
Morrison
G B
GB
NCI-Navy Medical Oncology Branch, National Cancer Institute in Bethesda, MD, USA.
Bastian
A
A
Dela Rosa
T
T
Diasio
R B
RB
Takimoto
C H
CH
D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000556:secondary; D042943:Dihydrouracil Dehydrogenase (NADP); D005260:Female; D005472:Fluorouracil / Q000009:adverse effects* / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008661:Metabolism, Inborn Errors / Q000150:complications*; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D010088:Oxidoreductases / Q000172:deficiency*; D010997:Pleural Neoplasms / Q000188:drug therapy / Q000556:secondary; D012720:Severity of Illness Index
D000964:Antimetabolites, Antineoplastic; D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil