5-FU is among the drugs most frequently used in the treatment of gastrointestinal malignancies. Also, it has been reported to reveal severe side effects in the case of a dihydropyrimidine dehydrogenase (DPD) deficiency. A 75-year-old man showed severe nausea and vomiting after administration of UFT/Uzel as adjuvant chemotherapy. Because of severe thrombocytopenia and grade 4 neutropenia, platelet transfusion and G-CSF administration were performed. With time, the leukocyte, neutrophil and platelet count recovered to normal level. We strongly suspected a DPD deficiency from the result of urinary pyrimidine analysis.
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Cancer Chemother Pharmacol
January 2025
Markey Cancer Center, University of Kentucky, Lexington, KY, USA.
Purpose: Patients with partial or complete DPD deficiency have decreased capacity to degrade fluorouracil and are at risk of developing toxicity, which can be even life-threatening.
Case: A 43-year-old man with moderately differentiated rectal adenocarcinoma on capecitabine presented to the emergency department with complaints of nausea, vomiting, diarrhea, weakness, and lower abdominal pain for several days. Laboratory findings include grade 4 neutropenia (ANC 10) and thrombocytopenia (platelets 36,000).
Cancer Chemother Pharmacol
January 2025
Service de Génomique des Tumeurs et Pharmacologie, Hôpital Saint-Louis, Assistance Publique Hôpitaux de Paris, Paris, France.
The enzyme dihydropyrimidine dehydrogenase (DPD) is the primary catabolic pathway of fluoropyrimidines including 5 fluorouracil (5FU) and capecitabine. Cases of lethal toxicity have been reported in cancer patients with complete DPD deficiency receiving standard dose of 5FU or capecitabine. DPD is encoded by the pharmacogene DPYD in which more than 200 variants have been identified.
View Article and Find Full Text PDFClin Oncol (R Coll Radiol)
December 2024
NHS North West Genomic Medicine Service Alliance, UK; Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester, UK; The Division of Evolution, Infection and Genomics, School of Biological Sciences, University of Manchester, Manchester, UK.
In 2020, the introduction of pre-emptive DPYD genotyping prior to the administration of systemic fluoropyrimidine-based chemotherapy represented one of the first widespread pharmacogenetic testing programmes to be applied nationally in the United Kingdom. Pharmacogenetic variants in the DPYD gene found in between 3 and 6% of the population are a recognised cause of primary DPD enzyme deficiency and associated increased risk of severe fluoropyrimidine toxicity [1]. Yet, the availability of testing globally is heterogeneous.
View Article and Find Full Text PDFbioRxiv
December 2024
Division of Applied Mathematics, Brown University, Providence, Rhode Island, United States.
Gaucher Disease (GD) is a rare genetic disorder characterized by a deficiency in the enzyme glucocerebrosidase, leading to the accumulation of glucosylceramide in various cells, including red blood cells (RBCs). This accumulation results in altered biomechanical properties and rheological behavior of RBCs, which may play an important role in blood rheology and the development of bone infarcts, avascular necrosis (AVN) and other bone diseases associated with GD. In this study, dissipative particle dynamics (DPD) simulations are employed to investigate the biomechanics and rheology of blood and RBCs in GD under various flow conditions.
View Article and Find Full Text PDFCancer Chemother Pharmacol
December 2024
Pharmacy Department, Centre Georges-François Leclerc, Dijon, France.
Objectives: The use of plasma uracil measurements to detect dihydropyrimidine dehydrogenase (DPD) deficiency is one of the methods for preventing toxicities associated with fluoropyrimidines, including 5-Fluorouracil (5-FU). Unfortunately, this measurement is subject to variations, that may lead to unnecessary dosage reductions and therefore to a reduced efficacy of treatment. Recently, new factors such as hepatic and renal impairment have been proposed as also influencing uracil concentration.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!