Dihydropyrimidine dehydrogenase deficiency and fluorouracil-related toxicity

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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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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...

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Familial Deficiency of Dihydropyrimidine Dehydrogenase

Severe neurotoxicity due to 5-fluorouracil (FUra) has previously been described in a patient with familial pyrimidinemia. We now report the biochemical basis for both the pyrimidinemia and neurotoxicity in a patient we have recently studied. After administration of a "test" dose of FUra (25 mg/m2, 600 gCi 16-3HJFUra by intravenous bolus) to a patient who had previously developed neurotoxicity a...

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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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ژورنال

عنوان ژورنال: British Journal of Cancer

سال: 1999

ISSN: 0007-0920,1532-1827

DOI: 10.1038/sj.bjc.6690098