A case–control study to assess the ability of the thymine challenge test to predict patients with severe to life threatening fluoropyrimidine‐induced gastrointestinal toxicity Article Swipe
Nuala A. Helsby
,
John A. Duley
,
Kathryn Burns
,
Claire Bonnet
,
Soo Hee Jeong
,
Elliott Brenman
,
Paula Barlow
,
Katrina Sharples
,
David Porter
,
Michael Findlay
·
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.1111/bcp.14153
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.1111/bcp.14153
Aims A previous study suggested that a thymine (THY) challenge dose could detect aberrant pharmacokinetics in known cases of fluoropyrimidine toxicity compared with healthy volunteers. The preliminary data suggested that urine sampling also could detect this aberrant disposition. The aim of this case–control study was to assess the ability of the urinary THY challenge test to discriminate cases of severe gastrointestinal toxicity in a cohort of patients treated with 5‐fluorouracil or capecitabine. Methods Patients ( n = 37) received a 250 mg ( per os ) dose of THY and a cumulative urine sample was collected for 0–4 h. The urinary amounts of THY and metabolite dihydrothymine (DHT) were determined by liquid chromatography/mass spectrometry. Genomic DNA was analysed for DPYD gene variants. Renal function was estimated from blood creatinine levels. Cases ( n = 9) and noncases ( n = 23) of severe (grade ≥ 3) gastrointestinal toxicity were defined based on Common Terminology Criteria for Adverse Events. Results The median THY/DHT ratios were 6.2 (interquartile range 2.9–6.4) in cases, including the 2 patients who were DPYD heterozygous carriers. However, this was not significantly different ( P = .07) from the THY/DHT in noncases (median 2.6, interquartile range 2.8–4.2). Although creatinine clearance was lower ( P = .001) in cases, renal function could not discriminate cases from noncases. However, logistic regression analysis using both of these explanatory variables could discriminate most cases (receiver operating characteristic area 0.8792, 95% confidence interval 0.72–1.00). Conclusions The THY challenge test combined with a patient's renal function may be useful as a phenotypic diagnostic test to detect risk of life‐threatening fluoropyrimidine gastrointestinal toxicity.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1111/bcp.14153
- https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bcp.14153
- OA Status
- bronze
- Cited By
- 6
- References
- 34
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2982454614
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W2982454614Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1111/bcp.14153Digital Object Identifier
- Title
-
A case–control study to assess the ability of the thymine challenge test to predict patients with severe to life threatening fluoropyrimidine‐induced gastrointestinal toxicityWork title
- Type
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articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2019Year of publication
- Publication date
-
2019-10-28Full publication date if available
- Authors
-
Nuala A. Helsby, John A. Duley, Kathryn Burns, Claire Bonnet, Soo Hee Jeong, Elliott Brenman, Paula Barlow, Katrina Sharples, David Porter, Michael FindlayList of authors in order
- Landing page
-
https://doi.org/10.1111/bcp.14153Publisher landing page
- PDF URL
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https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bcp.14153Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
bronzeOpen access status per OpenAlex
- OA URL
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https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bcp.14153Direct OA link when available
- Concepts
-
DPYD, Interquartile range, Medicine, Creatinine, Common Terminology Criteria for Adverse Events, Internal medicine, Confidence interval, Renal function, Toxicity, Gastroenterology, Urology, Urine, Surgery, Pharmacogenetics, Biology, Genotype, Biochemistry, GeneTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
6Total citation count in OpenAlex
- Citations by year (recent)
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2025: 2, 2024: 1, 2021: 2, 2020: 1Per-year citation counts (last 5 years)
- References (count)
-
34Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.sampling | 31 |
| abstract_inverted_index.toxicity | 20, 61, 147 |
| abstract_inverted_index.(receiver | 232 |
| abstract_inverted_index.carriers. | 178 |
| abstract_inverted_index.challenge | 9, 53, 244 |
| abstract_inverted_index.clearance | 201 |
| abstract_inverted_index.collected | 95 |
| abstract_inverted_index.different | 184 |
| abstract_inverted_index.estimated | 125 |
| abstract_inverted_index.including | 170 |
| abstract_inverted_index.noncases. | 217 |
| abstract_inverted_index.operating | 233 |
| abstract_inverted_index.patient's | 249 |
| abstract_inverted_index.suggested | 4, 28 |
| abstract_inverted_index.toxicity. | 267 |
| abstract_inverted_index.variables | 227 |
| abstract_inverted_index.variants. | 121 |
| abstract_inverted_index.2.9–6.4) | 167 |
| abstract_inverted_index.confidence | 238 |
| abstract_inverted_index.creatinine | 128, 200 |
| abstract_inverted_index.cumulative | 91 |
| abstract_inverted_index.determined | 109 |
| abstract_inverted_index.diagnostic | 258 |
| abstract_inverted_index.metabolite | 105 |
| abstract_inverted_index.phenotypic | 257 |
| abstract_inverted_index.regression | 220 |
| abstract_inverted_index.2.8–4.2). | 198 |
| abstract_inverted_index.Conclusions | 241 |
| abstract_inverted_index.Terminology | 153 |
| abstract_inverted_index.explanatory | 226 |
| abstract_inverted_index.preliminary | 26 |
| abstract_inverted_index.volunteers. | 24 |
| abstract_inverted_index.discriminate | 56, 214, 229 |
| abstract_inverted_index.disposition. | 37 |
| abstract_inverted_index.heterozygous | 177 |
| abstract_inverted_index.0.72–1.00). | 240 |
| abstract_inverted_index.capecitabine. | 71 |
| abstract_inverted_index.interquartile | 196 |
| abstract_inverted_index.significantly | 183 |
| abstract_inverted_index.spectrometry. | 113 |
| abstract_inverted_index.(interquartile | 165 |
| abstract_inverted_index.case–control | 42 |
| abstract_inverted_index.characteristic | 234 |
| abstract_inverted_index.dihydrothymine | 106 |
| abstract_inverted_index.5‐fluorouracil | 69 |
| abstract_inverted_index.fluoropyrimidine | 19, 265 |
| abstract_inverted_index.gastrointestinal | 60, 146, 266 |
| abstract_inverted_index.pharmacokinetics | 14 |
| abstract_inverted_index.life‐threatening | 264 |
| abstract_inverted_index.chromatography/mass | 112 |
| cited_by_percentile_year.max | 97 |
| cited_by_percentile_year.min | 89 |
| corresponding_author_ids | https://openalex.org/A5090098921 |
| countries_distinct_count | 2 |
| institutions_distinct_count | 10 |
| corresponding_institution_ids | https://openalex.org/I154130895 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/10 |
| sustainable_development_goals[0].score | 0.6700000166893005 |
| sustainable_development_goals[0].display_name | Reduced inequalities |
| citation_normalized_percentile.value | 0.63569326 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |