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

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