ArticleCancer chemotherapy and pharmacology2021
Comparison of a thymine challenge test and endogenous uracil-dihydrouracil levels for assessment of fluoropyrimidine toxicity risk.
Article in Cancer chemotherapy and pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
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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.
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Who cites it
3 citing papers in PubMed, 6 citations in OpenAlex.
- A thymine-challenge test to prospectively evaluate dihydropyrimidine dehydrogenase activity for risk of severe 5-fluorouracil-induced gastrointestinal toxicity.Cancer chemotherapy and pharmacology · 2025Trial
- Thymine as potential biomarker to predict 5-FU systemic exposure in patients with gastro-intestinal cancer: a prospective pharmacokinetic study (FUUT-trial).Cancer chemotherapy and pharmacology · 2025Article
- Severe 5-Fluorouracil-Associated Gastrointestinal Toxicity Unexplained by Dihydropyrimidine Dehydrogenase Deficiency and Renal Impairment: Should We Be Investigating Other Elimination Pathways to Assess the Risk of 5-Fluorouracil Toxicity?European journal of drug metabolism and pharmacokinetics · 2021Article
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeStandard dosages of fluoropyrimidine chemotherapy result in severe toxicity in a substantial proportion of patients, however, routine pre-therapeutic toxicity prediction remains uncommon. A thymine (THY) challenge test can discriminate risk of severe gastrointestinal toxicity in patients receiving fluoropyrimidine monotherapy. We aimed to measure endogenous plasma uracil (U) and its ratio to dihydrouracil (DHU), and assess the performance of these parameters compared with the THY challenge test to evaluate risk of severe toxicity.
methodsPlasma samples, previously collected from 37 patients receiving 5-fluorouracil (5-FU) or capecitabine monotherapy for a THY challenge test (ACTRN12615000586516; retrospectively registered), were assessed for endogenous plasma concentrations of U and DHU using a validated LC-MS/MS method. Renal function was estimated from blood creatinine, and patients with ≥ grade 3 toxicity (CTCAE v4.0) were classified as cases.
resultsThere were no differences in median endogenous U plasma concentrations or U/DHU ratios between severe toxicity cases and non-cases. Significant differences between cases and non-cases were noted when these measures were normalised to the estimated renal function (CrCL), U
conclusionsThe endogenous uracil-based parameters, adjusted to CrCL, were more predictive of increased risk of severe fluoropyrimidine toxicity than DPYD genotyping. However, endogenous U measurement detected fewer cases of severe toxicity than the THY challenge test.
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