Add like
Add dislike
Add to saved papers

Endogenous plasma and salivary uracil to dihydrouracil ratios and DPYD genotyping as predictors of severe fluoropyrimidine toxicity in patients with gastrointestinal malignancies.

Clinical Biochemistry 2016 November
OBJECTIVE: The aim of this study was to evaluate the use of plasma and saliva uracil (U) to dihydrouracil (UH2 ) metabolic ratio and DPYD genotyping, as a means to identify patients with dihydropyrimidine dehydrogenase (DPD) deficiency and fluoropyrimidine toxicity.

METHODS: Paired plasma and saliva samples were obtained from 60 patients with gastrointestinal cancer, before fluoropyrimidine treatment. U and UH2 concentrations were measured by LC-MS/MS. DPYD was genotyped for alleles *7, *2A, *13 and Y186C. Data on toxicity included grade 1 to 4 neutropenia, mucositis, diarrhea, nausea/vomiting and cutaneous rash.

RESULTS: 35% of the patients had severe toxicity. There was no variant allele carrier for DPYD. The [UH2 ]/[U] metabolic ratios were 0.09-26.73 in plasma and 0.08-24.0 in saliva, with higher correlation with toxicity grade in saliva compared to plasma (rs =-0.515 vs rs =-0.282). Median metabolic ratios were lower in patients with severe toxicity as compared to those with absence of toxicity (0.59 vs 2.83 saliva; 1.62 vs 6.75 plasma, P<0.01). A cut-off of 1.16 for salivary ratio was set (AUC 0.842), with 86% sensitivity and 77% specificity for the identification of patients with severe toxicity. Similarly, a plasma cut-off of 4.0 (AUC 0.746), revealed a 71% sensitivity and 76% specificity.

CONCLUSIONS: DPYD genotyping for alleles 7, *2A, *13 and Y186C was not helpful in the identification of patients with severe DPD deficiency in this series of patients. The [UH2 ]/[U] metabolic ratios, however, proved to be a promising functional test to identify the majority of cases of severe DPD activity, with saliva performing better than plasma.

Full text links

We have located links that may give you full text access.
Can't access the paper?
Try logging in through your university/institutional subscription. For a smoother one-click institutional access experience, please use our mobile app.

For the best experience, use the Read mobile app

Mobile app image

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app

All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

By using this service, you agree to our terms of use and privacy policy.

Your Privacy Choices Toggle icon

You can now claim free CME credits for this literature searchClaim now

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app