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. 2022 Jan 26;29(2):497-509.
doi: 10.3390/curroncol29020045.

Upfront DPYD Genotyping and Toxicity Associated with Fluoropyrimidine-Based Concurrent Chemoradiotherapy for Oropharyngeal Carcinomas: A Work in Progress

Antoine Desilets  1 , William McCarvill  1 , Francine Aubin  1 , Houda Bahig  1 , Olivier Ballivy  1 , Danielle Charpentier  1 , Édith Filion  1 , Rahima Jamal  1 , Louise Lambert  1 , Phuc Felix Nguyen-Tan  1 , Charles Vadnais  1 , Xiaoduan Weng  1 , Denis Soulières  1
Affiliations

Upfront DPYD Genotyping and Toxicity Associated with Fluoropyrimidine-Based Concurrent Chemoradiotherapy for Oropharyngeal Carcinomas: A Work in Progress

Antoine Desilets et al. Curr Oncol. .

Abstract

Background: 5-FU-based chemoradiotherapy (CRT) could be associated with severe treatment-related toxicities in patients harboring at-risk DPYD polymorphisms. Methods: The studied population included consecutive patients with locoregionally advanced oropharyngeal carcinoma treated with carboplatin and 5-FU-based CRT one year before and after the implementation of upfront DPYD*2A genotyping. We aimed to determine the effect of DPYD genotyping on grade ≥3 toxicities. Results: 181 patients were analyzed (87 patients before and 94 patients following DPYD*2A screening). Of the patients, 91% (n = 86) were prospectively genotyped for the DPYD*2A allele. Of those screened, 2% (n = 2/87) demonstrated a heterozygous DPYD*2A mutation. Extended genotyping of DPYD*2A-negative patients later allowed for the retrospective identification of six additional patients with alternative DPYD variants (two c.2846A>T and four c.1236G>A mutations). Grade ≥3 toxicities occurred in 71% of the patients before DPYD*2A screening versus 62% following upfront genotyping (p = 0.18). When retrospectively analyzing additional non-DPYD*2A variants, the relative risks for mucositis (RR 2.36 [1.39-2.13], p = 0.0063), dysphagia (RR 2.89 [1.20-5.11], p = 0.019), and aspiration pneumonia (RR 13 [2.42-61.5)], p = 0.00065) were all significantly increased. Conclusion: The DPYD*2A, c.2846A>T, and c.1236G>A polymorphisms are associated with an increased risk of grade ≥3 toxicity to 5-FU. Upfront DPYD genotyping can identify patients in whom 5-FU-related toxicity should be avoided.

Keywords: DPYD; chemoradiotherapy; fluoropyrimidine; genotyping; head and neck cancer; oropharyngeal cancer; pharmacovigilance.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
CONSORT Diagram. This diagram illustrates patients’ flow following initial DPYD screening and subsequent treatment according to the presence of the DPYD*2A polymorphism. Toxicities were compared between the screening cohort and a local cohort consisting of retrospectively identified patients treated with carboplatin and 5-FU-based chemoradiation. Screening for additional at-risk DPYD variants was later retrospectively performed in June 2018.
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