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Clinical Benefits and Utility of Pretherapeutic DPYD and UGT1A1 Testing in Gastrointestinal Cancer: A Secondary Analysis of the PREPARE Randomized Clinical Trial.
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.
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 PDFCorrection: Nelson et al. Guided Cancer Therapy: Review of the Evidence and Considerations for Clinical Implementation. 2021, , 1566.
Cancers (Basel)
October 2024
Department of Individualized Cancer Management, Moffitt Cancer Center, Tampa, FL 33612, USA.
In the original publication [...
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 PDFArticle Synopsis
- * A pilot program was launched where pharmacists reviewed genetic test results, provided drug-dosing advice, and documented interactions in patient records, which were shared with oncologists.
- * Results showed that out of 71 patients, 21 had actionable genetic variants, leading to dose changes in five patients, demonstrating the potential of pharmacist involvement in personalized medicine.
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