Evidence map›Paper›PMID 33620159›Full record

ArticleClinical and translational science2021

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

Theodore J Wigle, Brandi L Povitz, Samantha Medwid, Wendy A Teft, Robin M Legan, John Lenehan, Stephanie Nevison, Veera Panuganty, Denise Keller, Jaymie Mailloux and 7 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical and translational science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 1 pooled it
3.3field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.

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  20. Current oncology (Toronto, Ont.) · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 4 institutions in 1 country.

Theodore J WigleDepartment of Physiology and Pharmacology, University of Western Ontario, London, Canada.
Brandi L PovitzLawson Health Research Institute, London, Canada.
Samantha MedwidDepartment of Physiology and Pharmacology, University of Western Ontario, London, Canada.
Wendy A TeftDepartment of Medicine, University of Western Ontario, London, Canada.
Robin M LeganDepartment of Medicine, University of Western Ontario, London, Canada.
John LenehanDepartment of Oncology, University of Western Ontario, London, Canada.
Stephanie NevisonSchool of Medicine, University of Toronto, Mississauga, Canada.
Veera PanugantyDepartment of Oncology, University of Western Ontario, London, Canada.
Denise KellerLondon Health Sciences Centre, London, Canada.
Jaymie MaillouxDepartment of Physiology and Pharmacology, University of Western Ontario, London, Canada.
Victoria SiebringLondon Health Sciences Centre, London, Canada.
Sisira SarmaDepartment of Epidemiology and Biostatistics, University of Western Ontario, London, Canada.
Yun-Hee ChoiDepartment of Epidemiology and Biostatistics, University of Western Ontario, London, Canada.
Stephen WelchDepartment of Oncology, University of Western Ontario, London, Canada.
Eric WinquistDepartment of Oncology, University of Western Ontario, London, Canada.
Ute I SchwarzDepartment of Medicine, University of Western Ontario, London, Canada.
Richard B KimDepartment of Physiology and Pharmacology, University of Western Ontario, London, Canada.
Western University · CALondon Health Sciences Centre · CALawson Health Research Institute · CAUniversity of Toronto · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Consensus guidelines exist for genotype-guided fluoropyrimidine dosing based on variation in the gene dihydropyrimidine dehydrogenase (DPYD). However, these guidelines have not been widely implemented in North America and most studies of pretreatment DPYD screening have been conducted in Europe. Given regional differences in treatment practices and rates of adverse events (AEs), we investigated the impact of pretreatment DPYD genotyping on AEs in a Canadian context. Patients referred for DPYD genotyping prior to fluoropyrimidine treatment were enrolled from December 2013 through November 2019 and followed until completion of fluoropyrimidine treatment. Patients were genotyped for DPYD c.1905+1G>A, c.2846A>T, c.1679T>G, and c.1236G>A. Genotype-guided dosing recommendations were informed by Clinical Pharmacogenetics Implementation Consortium guidelines. The primary outcome was the proportion of patients who experienced a severe fluoropyrimidine-related AE (grade ≥3, Common Terminology Criteria for Adverse Events version 5.0). Secondary outcomes included early severe AEs, severe AEs by toxicity category, discontinuation of fluoropyrimidine treatment due to AEs, and fluoropyrimidine-related death. Among 1394 patients, mean (SD) age was 64 (12) years, 764 (54.8%) were men, and 47 (3.4%) were DPYD variant carriers treated with dose reduction. Eleven variant carriers (23%) and 418 (31.0%) noncarriers experienced a severe fluoropyrimidine-related AE (p = 0.265). Six carriers (15%) and 284 noncarriers (21.1%) experienced early severe fluoropyrimidine-related AEs (p = 0.167). DPYD variant carriers treated with genotype-guided dosing did not experience an increased risk for severe AEs. Our data support a role for DPYD genotyping in the use of fluoropyrimidines in North America.

Indexed as

AgedAntimetabolites, AntineoplasticCanadaCapecitabineDihydropyrimidine Dehydrogenase DeficiencyDihydrouracil Dehydrogenase (NADP)FemaleFluorouracilHeterozygoteHumansMaleMedical OncologyMiddle AgedNeoplasmsPharmacogenomic TestingPharmacogenomic VariantsAntimetabolites, AntineoplasticCapecitabineDihydrouracil Dehydrogenase (NADP)Fluorouracil

Identifiers

PMID33620159
PMCPMC8301551
OpenAlexW3129455772

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.