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Colorectal cancer is the second most common cancer in Europe. Most antineoplastic regimens in first-line treatment involve 5-fluorouracil or oral prodrug capecitabine, combined with other antineoplastic agents such as oxaliplatin or irinotecan. It is well known that 5-fluorouracil and capecitabine are agents that can be toxic in cases of decreased dihydropyrimidine dehydrogenase activity because this enzyme is the main limiting factor in the metabolism of both agents. In this paper, we describe the case of a patient who developed severe toxicity to 5-fluouracil and who had a mutation in the gene encoding the enzyme dihydropyrimidine dehydrogenase.
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http://dx.doi.org/10.1177/1078155216647202 | DOI Listing |
Oncol Lett
February 2025
Division of Surgery, Orthopaedics and Oncology, Department of Biomedical and Clinical Sciences, Linköping University, SE-58185 Linköping, Sweden.
Pancreatic ductal adenocarcinoma (PDAC) is associated with a poor prognosis, and biomarkers to guide treatment decisions in PDAC are generally lacking. Intratumoural expression of dihydropyrimidine dehydrogenase (DPD) is a potential prognostic parameter in patients with PDAC undergoing surgical resection and postoperative chemotherapy. In the present study, DPD was analysed by immunohistochemistry of a tissue microarray platform including a real-world cohort of 495 patients with PDAC who had undergone resection with curative intent at any of three tertiary centres, including Northern, Western and Southeastern regions of Sweden, between 1993 and 2019.
View Article and Find Full Text PDFFront Pharmacol
December 2024
Experimental and Clinical Pharmacology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Province of Pordenone, Italy.
Dihydropyrimidine dehydrogenase (DPD, encoded by the gene) is the rate-limiting enzyme for the detoxification of fluoropyrimidines (FLs). Rs4294451 is a regulatory polymorphism that has recently been functionally characterized and associated with increased DPD expression in the liver. The aim of the present study was to test the clinical implications of being a carrier of rs4294451 in a cohort of 645 FL-treated colorectal cancer patients.
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 PDFCancer Chemother Pharmacol
December 2024
Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand.
DPYD polymorphisms have been widely found to be related to 5-FU-induced toxicities. The aim of this study was to establish significant associations between five single-nucleotide polymorphisms of DPYD and 5-FU hematological toxicities in Thai colorectal cancer patients. The toxicities were analyzed at the first and second cycles of 5-FU administration in 75 patients.
View Article and Find Full Text PDFJ Chromatogr A
December 2024
Department of Medicinal and Applied Chemistry, Kaohsiung Medical University (KMU), Kaohsiung City-807, Taiwan; Research Center for Precision Environmental Medicine, College of Medicine, Kaohsiung Medical University (KMU), Kaohsiung City-807, Taiwan; PhD Program in Environmental and Occupational Medicine, College of Medicine, Kaohsiung Medical University (KMU), Kaohsiung City-807, Taiwan; Department of Medical Research, Kaohsiung Medical University Hospital (KMUH), Kaohsiung Medical University, Kaohsiung, City-807, Taiwan; Department of Chemistry, National Sun Yat-sen University (NSYSU), Kaohsiung City, 804, Taiwan. Electronic address:
Patients with dihydropyrimidine dehydrogenase (DPD) deficiency in peripheral mononuclear cells are at higher risk of severe toxicity due to the improper dose of fluorouracil-based chemotherapy drugs, which has become an essential aspect for consideration in clinical studies. 5-fluorouracil (5-FU) is a first-line and second-line chemotherapy drug in adjuvant, neoadjuvant, or palliative therapy settings to treat solid tumors and cancers. In this work, a novel in-syringe-based fast drug extraction (IS-FaDEx) technique followed by UHPLC-MS/MS detection was developed for rapid biomonitoring of 5-FU and its biometabolites in human blood samples.
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