Dataset Information

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.

ABSTRACT:

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.

SUBMITTER: Helsby NA

PROVIDER: S-EPMC6983507 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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.

Helsby Nuala A NA Duley John J Burns Kathryn E KE Bonnet Claire C Jeong Soo Hee SH Brenman Elliott E Barlow Paula P Sharples Katrina K Porter David D Findlay Michael M

British journal of clinical pharmacology 20191212 1

<h4>Aims</h4>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 cap ...[more]

PMID: 31658382

Similar Datasets

Project description:Interventions: This study is an observational study. Thymine test results will not affect any treatment decisions. At a scheduled assessment clinic visit, >24 hours prior to the commencement of treatment with 5-FU/capecitabine containing schedules: A baseline blood sample will be obtained (one 10 ml sample) as well as a baseline spot urine sample. A cheek (buccal) cell sample will also be obtained. This will involve using a cytobrush to take a brushing of the inside of the cheek (like using a toothbrush on the inside of the mouth). This will be done twice (one on each side of the mouth) and will require a mouth wash with water prior to the first brushing. The participants will then be administered thymine (250 mg, oral gelatine capsule) with a drink of water. A cumulative (total) urine sample will be collected for the next 4 hours. All patients who have been given the thymine test will then continue on their planned chemotherapy treatment. All patients will be assessed for adverse events related to 5-FU/capecitabine treatment. Information will be collected at each scheduled clinic visit for 8 – 9 weeks while on normal chemotherapy treatment. Analysis will involve urine sample for thymine and its metabolite (dihydrothymine or DHT). Cheek cells will be used to assess 5-FU uptake in vitro and genomic DNA (from blood) will be used to analysing variation in the DPYD gene and further analysis of genes associated with 5-FU side effects. Primary outcome(s): The primary outcome is the presence of severe DM toxicity. All diarrhoea (D) and mucositis (M) toxicities will be identified and coded according to CTCAE criteria. Patients with grade 2 or less GI events or haematotoxicity, or grade 1 or less hand-foot syndrome will be coded as minimal toxicity. For patients with a Grade 3 or higher D or M toxicity a review will be carried out by a clinical PI (blinded to thymine test results and genomic information).[Information will be collected at each scheduled clinic visit for 8 – 9 weeks while on normal chemotherapy treatment. ] Study Design: Purpose: Natural history;Duration: Longitudinal;Selection: Defined population;Timing: Prospective

Dataset Information

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.

Aims

Methods

Results

Conclusions

Publications

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.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets