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Impact of Upfront DPYD Genotyping on Fluoropyrimidine Adjuvant Therapy in Colorectal Cancer: A Real-World Data.
Clin Colorectal Cancer
February 2025
Department of Oncology, The Wellbeing Services County of Ostrobothnia, Vaasa Central Hospital, Vaasa, Finland.
Background: The application of fluoropyrimidine-based chemotherapy in colorectal cancer treatment is known to pose significant toxicity risks, which can be mitigated by tailoring treatment according to DPYD gene variants. This study evaluates the impact of DPYD genotype-guided dosing on treatment-related toxicities and patient outcomes.
Methods: A retrospective analysis was conducted on CRC patients treated with fluoropyrimidines in adjuvant setting at The Wellbeing Services County of Ostrobothnia.
Severe fluoropyrimidine toxicity in older adults with cancer with DPYD wild type.
Fundam Clin Pharmacol
April 2025
Department of Internal Medicine - Medical Oncology, University Medical Center Leiden, RC, Leiden, the Netherlands.
Background: Despite the implementation of DPYD genotype-guided dosing, approximately 1 in 3 patients receiving fluoropyrimidine-containing chemotherapy continues to experience severe toxicity. While clinical studies have demonstrated a favorable tolerance among highly selected fit older adults, real-world studies have shown an increased risk of toxicity.
Objective: To identify predictors of severe toxicity or treatment deintensification in older DPYD wild-type adults receiving fluoropyrimidine-containing chemotherapy.
Pharmacogenetic-guided dosing for fluoropyrimidine (DPYD) and irinotecan (UGT1A1*28) chemotherapies for patients with cancer (PACIFIC-PGx): A multicenter clinical trial.
Clin Transl Sci
December 2024
Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia.
PACIFIC-PGx evaluated the feasibility of implementing pharmacogenetics (PGx) screening in Australia and the impact of DPYD/UGT1A1 genotype-guided dosing on severe fluoropyrimidine (FP) and irinotecan-related toxicities and hospitalizations, compared to historical controls. This prospective single arm trial enrolled patients starting FP/irinotecan for any cancer between 7 January 2021 and 25 February 2022 from four Australian hospitals (one metropolitan, three regional). During the accrual period, 462/487 (95%) consecutive patients screened for eligibility for DPYD and 50/109 (46%) for UGT1A1 were enrolled and genotyped (feasibility analysis), with 276/462 (60%) for DPYD and 30/50 (60%) for UGT1A1 received FP/irinotecan (safety analysis).
View Article and Find Full Text PDFDPYD genotype-guided dose personalisation for fluoropyrimidine-based chemotherapy prescribing in solid organ cancer patients in Australia: GeneScreen 5-FU study protocol.
BMC Cancer
November 2024
University of Newcastle, College of Health, Medicine and Wellbeing, School of Biomedical Science and Pharmacy, Callaghan, NSW, 2308, Australia.
Background: Fluoropyrimidine (FP) chemotherapies are commonly prescribed for upper and lower gastrointestinal, breast and head and neck malignancies. Over 16,000 people with cancer require FP chemotherapies per annum in Australia. Between 10 and 40% patients experience grade 3-4 (≥ G3) toxicities that require hospital-based management ± intensive care admission.
View Article and Find Full Text PDFNovel Genetic Variants Explaining Severe Adverse Drug Events after Clinical Implementation of Genotype-Guided Therapy with Fluoropyrimidines: An Observational Study.
Pharmaceutics
July 2024
Instituto de Investigación Biosanitaria de Granada (Ibs.Granada), 18012 Granada, Spain.
Fluoropyrimidines (FPs) are commonly prescribed in many cancer streams. The EMA and FDA-approved drug labels for FPs recommend genotyping the *2A (rs3918290), *13 (rs55886062), *HapB3 (rs56038477), alleles, and rs67376798 before treatment starts. We implemented the genotyping in our daily clinical routine, but we still found patients showing severe adverse drug events (ADEs) to FPs.
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