5-Fluorouracil Toxicity and Dihydropyrimidine Dehydrogenase Enzyme: Implications for Practice

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5-Fluorouracil toxicity and dihydropyrimidine dehydrogenase enzyme: implications for practice.

5-fluorouracil (5-FU) is a fluorinated pyrimidine analog, which is commonly used in combination chemotherapy for treating solid tumors. Dihydropyrimidine dehydrogenase plays an important role in catabolism and clearance of 5-FU. Any alteration in that sequence of enzymatic activity can lead to toxicity and even death in some patients. The most common loss of a functional allele of the dihydropy...

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cDNA cloning and chromosome mapping of human dihydropyrimidine dehydrogenase, an enzyme associated with 5-fluorouracil toxicity and congenital thymine uraciluria.

The pig and human dihydropyrimidine dehydrogenase (DPD) cDNAs were cloned and sequenced. The pig enzyme, expressed in Escherichia coli, catalyzed the reduction of uracil, thymine, and 5-fluorouracil with kinetics approximating those published for the enzyme purified from mammalian liver. DPD could be expressed in significant quantities only when uracil was added to the bacterial growth medium. ...

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Dihydropyrimidine dehydrogenase: its role in 5-fluorouracil clinical toxicity and tumor resistance.

DPD (also known as dihydrouracil dehydrogenase, dihydrothymine dehydrogenase, and uracil reductase; EC 1.3.1.2) is the initial enzyme and the rate-limiting step in the pyrimidine catabolic pathway (1). Studies over the past two decades have demonstrated that DPD is an important regulatory enzyme in the metabolism of both the naturally occurring pyrimidines uracil and thymine as well as the canc...

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Life-threatening toxicity in a dihydropyrimidine dehydrogenase-deficient patient after treatment with topical 5-fluorouracil.

In humans, 80-90% of an administered dose of 5-fluorouracil (5-FU) is degraded by dihydropyrimidine dehydrogenase (DPD; EC 1.3.1.2), the initial rate-limiting enzyme in pyrimidine catabolism. Cancer patients with decreased DPD activity are at increased risk for severe toxicity including diarrhea, stomatitis, mucositis, myelosuppression, neurotoxicity, and, in some cases, death. We now report th...

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Dihydropyrimidine dehydrogenase activity: prognostic partner of 5-fluorouracil?

5-FU is one of the most commonly prescribed anticancer agents having notable activity in the treatment of cancers arising from the breast, gastrointestinal tract, and head and neck. The metabolism, mechanisms of action and resistance, and pharmacokinetics of 5-FU have been extensively investigated since its synthesis over 4 decades ago. Despite a longstanding knowledge of the metabolic pathways...

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ژورنال

عنوان ژورنال: Clinical Journal of Oncology Nursing

سال: 2014

ISSN: 1092-1095,1538-067X

DOI: 10.1188/14.cjon.581-585