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Parenteral 5-fluorouracil (5-FU) is part of the standard treatment for various malignant tumors (such as colorectal cancer, pancreatic cancer, gastric cancer, breast cancer, and head and neck cancers) and is most often used in combination with other chemotherapy agents.If uracil levels are used to determine DPD phenotype, the phenotype results should be interpreted cautiously in patients with moderate or severe renal impairment.If severe toxicity does not occur, subsequent doses may be increased, as the efficacy of conventionally lower doses has not been established.Patients with impaired DPD enzyme activity have an increased risk of severe or life-threatening toxicity when treated with 5-FU or any of its prodrugs.Dihydropyrimidine dehydrogenase (DPD) is an enzyme that affects the degradation rate of 5-FU.
Parenteral 5-fluorouracil (5-FU) is part of the standard treatment for various malignant
tumors (such as colorectal cancer, pancreatic cancer, gastric cancer, breast cancer, and
head and neck cancers) and is most often used in combination with other chemotherapy
agents.
Dihydropyrimidine dehydrogenase (DPD) is an enzyme that affects the degradation rate of 5-FU.
Patients with impaired DPD enzyme activity have an increased risk of severe
or life-threatening toxicity when treated with 5-FU or any of its prodrugs.
Therefore, phenotyping and/or genotyping is recommended before starting treatment.
Although there is no certainty about the optimal testing method, it is recommended
to test for DPD deficiency before treatment to identify patients at risk of severe toxicity.
Patients with complete DPD deficiency have a high risk of life-threatening or
fatal toxicity, and therefore should not be treated with 5-FU or other
fluoropyrimidines (capecitabine, tegafur).
Patients with partial DPD deficiency have a conventionally higher risk of severe and
potentially life-threatening toxicity. To reduce the risk of severe toxicity, consideration
should be given to a conventionally lower starting dose. If severe toxicity does not
occur, subsequent doses may be increased, as the efficacy of conventionally
lower doses has not been established. Renal impairment can elevate blood uracil levels. If uracil levels are used to determine
DPD phenotype, the phenotype results should be interpreted cautiously in patients
with moderate or severe renal impairment. The risk of misdiagnosing DPD deficiency in
this patient group increases and may lead to underdosing of 5-FU or other
fluoropyrimidines
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