Evidence map›Paper›PMID 33687515›Full record

ArticleCancer chemotherapy and pharmacology2021

Comparison of a thymine challenge test and endogenous uracil-dihydrouracil levels for assessment of fluoropyrimidine toxicity risk.

Kathryn E Burns, Ottiniel Chavani, Soo Hee Jeong, John A Duley, David Porter, Michael Findlay, R Matthew Strother, Nuala A Helsby

Abstract readComparative Study
PubMed Publisher
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 43% 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

3 citing papers in PubMed, 6 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
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

8 authors at 5 institutions in 2 countries.

Kathryn E BurnsDepartment of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.ORCID http://orcid.org/0000-0003-4951-3539
Ottiniel ChavaniCanterbury Health Laboratories, Christchurch, New Zealand.ORCID http://orcid.org/0000-0002-5843-3517
Soo Hee JeongDepartment of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.ORCID http://orcid.org/0000-0002-5984-1280
John A DuleySchool of Pharmacy, University of Queensland, Brisbane, Australia.
David PorterCancer and Blood, Auckland City Hospital, Grafton, Auckland, New Zealand.ORCID http://orcid.org/0000-0002-3115-8244
Michael FindlayCancer and Blood, Auckland City Hospital, Grafton, Auckland, New Zealand.ORCID http://orcid.org/0000-0002-3305-9768
R Matthew StrotherDepartment of Oncology, Canterbury District Health Board and Department of Medicine, University of Otago, Christchurch, New Zealand.ORCID http://orcid.org/0000-0001-8118-8954
Nuala A HelsbyDepartment of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. n.helsby@auckland.ac.nz.ORCID http://orcid.org/0000-0001-6570-5368
University of Auckland · NZAuckland City Hospital · NZCanterbury District Health Board · NZCanterbury Health Laboratories · NZThe University of Queensland · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

CapecitabineDihydrouracil Dehydrogenase (NADP)FluorouracilGenotypeHumansThymineUracilCapecitabinedihydrouracilDihydrouracil Dehydrogenase (NADP)FluorouracilThymineUracil5-FU toxicityDihydrouracilDihydrouracil/uracil ratioThymineUracil

Identifiers

PMID33687515
OpenAlexW3133846557

What OpenQuestion holds

Textmetadata
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.