Aim: Fluoropyrimidines are commonly used anti-cancer drugs, but lead to severe toxicity in 10-30% of patients. Prospective DPYD screening identifies patients at risk for toxicity and leads to a safer treatment with fluoropyrimidines. This study evaluated the routinely application of prospective DPYD screening at the Leiden University Medical Center.
Methods: Prospective DPYD screening as part of routine patient care was evaluated by retrospectively screening databases and patient files to determine genotype, treatment, dose recommendations and dose adjustments.
Results: 86.9% of all patients with a first fluoropyrimidine prescription were screened. Fourteen out of 275 patients (5.1%) carried a DPYD variant and received a 25-50% dose reduction recommendation. None of the patients with a DPYD variant treated with a reduced dose developed toxicities.
Conclusion: Prospective DPYD screening can be implemented successfully in a real world clinical setting, is well accepted by physicians and results in low toxicity.
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http://dx.doi.org/10.2217/pgs-2016-0013 | DOI Listing |
JAMA Netw Open
December 2024
Experimental and Clinical Pharmacology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy.
Importance: To date, the clinical benefit and utility of implementing a DPYD/UGT1A1 pharmacogenetic-informed therapy with fluoropyrimidines and/or irinotecan have not been prospectively investigated.
Objective: To examine clinically relevant toxic effects, hospitalizations, and related costs while preserving treatment intensity and efficacy outcomes in patients with gastrointestinal cancer.
Design, Setting, And Participants: This nonprespecified secondary analysis stems from Pre-Emptive Pharmacogenomic Testing for Preventing Adverse Drug Reactions (PREPARE), a multicenter, controlled, open, block-randomized, crossover implementation trial conducted from March 7, 2017, to June 30, 2020, and includes data from Italy according to a sequential study design.
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 PDFBMC 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 PDFBMC Cancer
September 2024
Ophir Loyola Hospital, Belém, 66063-240, Pará, Brazil.
Genome Med
August 2024
Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands.
Background: The Alpe-DPD study (NCT02324452) demonstrated that prospective genotyping and dose-individualization using four alleles in DPYD (DPYD*2A/rs3918290, c.1236G > A/rs75017182, c.2846A > T/rs67376798 and c.
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