Impact of pretreatment dihydropyrimidine dehydrogenase genotype‐guided fluoropyrimidine dosing on chemotherapy associated adverse events

Wigle, Theodore J.; Povitz, Brandi; Medwid, Samantha; Teft, Wendy A.; Legan, Robin M.; Lenehan, John; Nevison, Stephanie; Panuganty, Veera; Keller, Denise; Mailloux, Jaymie; Siebring, Victoria; Sarma, Sisira; Choi, Yun Hee; Welch, Stephen; Winquist, Eric; Schwarz, Ute I.; Kim, Richard B.

doi:10.1111/cts.12981

“…The fluoropyrimidines (FP), 5-fluorouracil and its oral pro-drug capecitabine, constitute the backbone of many standard chemotherapy regimens for the treatment of certain solid tumors such as head and neck, gastrointestinal tract, breast and pancreatic cancers ( Froehlich et al, 2015 ; Wigle et al, 2021 ). However, the occurrence of severe FP-related toxicities in 10%–40% of patients (depending on the treatment regimen) are an important drawback of these drugs, causing severe morbidity or treatment cessation ( Froehlich et al, 2015 ; Amstutz et al, 2018 ; Henricks et al .…”

Section: Introductionmentioning

confidence: 99%

Clinical Implementation of DPYD Pharmacogenetic Testing to Prevent Early-Onset Fluoropyrimidine-Related Toxicity in Cancer Patients in Switzerland

Begré

¹

,

Jörger

²

,

Aebi

³

et al. 2022

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The implementation of pharmacogenetic testing into clinical practice has been a slow process so far. Here, we review the implementation of pre-treatment testing of dihydropyrimidine dehydrogenase gene (DPYD) risk variants to prevent early-onset fluoropyrimidine (FP)-related toxicity in cancer patients in Switzerland based on data of a large Swiss diagnostic center. In January 2017, the Swiss Federal Office of Public Health introduced the reimbursement of DPYD testing by the compulsory health insurance in Switzerland based on evidence for the clinical relevance of DPYD-risk variants and the cost-effectiveness of pre-treatment testing, and on the availability of international guidelines. However, we did not observe a strong increase in DPYD testing at our diagnostic center from 2017 to 2019. Only a low number of DPYD-testing requests (28–42 per year), concerning mostly retrospective investigations of suspected FP-toxicity, were received. In contrast, we observed a 14-fold increase in DPYD testing together with a strong shift from retrospective to pre-treatment test requests upon the release of recommendations for DPYD testing prior to FP-treatment in April 2020 by the European Medicines Agency. This increase was mainly driven by three geographic regions of Switzerland, where partner institutions of previous research collaborations regarding FP-related toxicity are located and who acted as early-adopting institutions of DPYD testing. Our data suggest the important role of early adopters as accelerators of clinical implementation of pharmacogenetic testing by introducing these policies to their working environment and educating health workers from their own and nearby institutions.

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“…A recent analysis confirmed that carriers of decreased function or no function alleles for DPYD were at significantly increased risk of both severe toxicity and treatment modifications with fluoropyrimidine therapy compared to non-carriers (24). Wigle and colleagues reported outcomes comparing genotype-guided dosing of fluoropyrimidine therapy and noted the individuals prescribed guideline-based dose reductions experienced similar rates of serious adverse events as wild type individuals prescribed standard dosages (25). This drug-gene association yields sufficient data to warrant clinical guidelines from the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Royal Dutch Association for the Advancement of Pharmacy-Pharmacogenetics Working Group (DPWG).…”

Section: Original Articlementioning

confidence: 99%

The effect of medication reconciliation on generating an accurate medication list in a pharmacogenomics practice

Petry¹,

Heukelom²,

Baye³

et al. 2022

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Background: Medication reconciliation is recognized as a critically important medication safety element and a key initiative by multiple organizations. Within our precision medicine program, accurate medication lists are essential to our ability to make specific medication recommendations based on pharmacogenetic results. Our study aimed to identify discrepancies within the patient's medication list to improve medication management via genetic factors through a pharmacy team-based approach.Methods: A dedicated team of pharmacists and trained student pharmacists conducted telephone interviews to complete medication reconciliation for individuals enrolled in our precision medicine preemptive screening program. Medication list discrepancies were tracked as well as if pharmacogenetic consults were altered by findings during the telephone interviews.Results: Medication reconciliation was completed on 465 participants who had recently received or were awaiting pharmacogenetic testing. We found similar results to previously described rates of medication list discrepancies with an average of 4.9 medication discrepancies per patient as well as greater than 90% of individuals having at least one medication discrepancy. Pharmacogenetic recommendations for 20 individuals (4.3%) required adjustment following medication reconciliation.Conclusions: This pilot program supports the value of a dedicated team for medication reconciliation and the importance of accurate medication lists to optimize precision medicine programs.

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“…A recent analysis confirmed that carriers of decreased function or no function alleles for DPYD were at significantly increased risk of both severe toxicity and treatment modifications with fluoropyrimidine therapy compared to non-carriers (24). Wigle and colleagues reported outcomes comparing genotype-guided dosing of fluoropyrimidine therapy and noted the individuals prescribed guideline-based dose reductions experienced similar rates of serious adverse events as wild type individuals prescribed standard dosages (25). This drug-gene association yields sufficient data to warrant clinical guidelines from the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Royal Dutch Association for the Advancement of Pharmacy-Pharmacogenetics Working Group (DPWG).…”

Section: Original Articlementioning

confidence: 99%

The effect of medication reconciliation on generating an accurate medication list in a pharmacogenomics practice

Petry¹,

Heukelom²,

Baye³

et al. 2021

Pharmacogenet Res Per Med

View full text Add to dashboard Cite

Background: Medication reconciliation is recognized as a critically important medication safety element and a key initiative by multiple organizations. Within our precision medicine program, accurate medication lists are essential to our ability to make specific medication recommendations based on pharmacogenetic results. Our study aimed to identify discrepancies within the patient's medication list to improve medication management via genetic factors through a pharmacy team-based approach.Methods: A dedicated team of pharmacists and trained student pharmacists conducted telephone interviews to complete medication reconciliation for individuals enrolled in our precision medicine preemptive screening program. Medication list discrepancies were tracked as well as if pharmacogenetic consults were altered by findings during the telephone interviews.Results: Medication reconciliation was completed on 465 participants who had recently received or were awaiting pharmacogenetic testing. We found similar results to previously described rates of medication list discrepancies with an average of 4.9 medication discrepancies per patient as well as greater than 90% of individuals having at least one medication discrepancy. Pharmacogenetic recommendations for 20 individuals (4.3%) required adjustment following medication reconciliation.Conclusions: This pilot program supports the value of a dedicated team for medication reconciliation and the importance of accurate medication lists to optimize precision medicine programs.

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Impact of pretreatment dihydropyrimidine dehydrogenase genotype‐guided fluoropyrimidine dosing on chemotherapy associated adverse events

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 31 publications

References 21 publications

Clinical Implementation of DPYD Pharmacogenetic Testing to Prevent Early-Onset Fluoropyrimidine-Related Toxicity in Cancer Patients in Switzerland

Clinical Implementation of DPYD Pharmacogenetic Testing to Prevent Early-Onset Fluoropyrimidine-Related Toxicity in Cancer Patients in Switzerland

The effect of medication reconciliation on generating an accurate medication list in a pharmacogenomics practice

The effect of medication reconciliation on generating an accurate medication list in a pharmacogenomics practice

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