Title :

Complete DPYD genotyping combined with dihydropyrimidine dehydrogenase phenotyping to prevent fluoropyrimidine toxicity: A retrospective study.

Author(s) :

De Metz, Côme [Auteur]
Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] [UNICANCER/Lille]
Hennart, Benjamin [Auteur]
IMPact de l'Environnement Chimique sur la Santé humaine (IMPECS) - ULR 4483
Aymes, Estelle [Auteur]
Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] [UNICANCER/Lille]
Cren, Pierre-Yves [Auteur]
Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] [UNICANCER/Lille]
Martignène, Niels [Auteur]
Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] [UNICANCER/Lille]
Penel, Nicolas [Auteur]
Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS]
Barthoulot, Mael [Auteur]
Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] [UNICANCER/Lille]
Carnot, Aurélien [Auteur]
Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] [UNICANCER/Lille]

Journal title :

Cancer Medicine

Abbreviated title :

Cancer Med

Volume number :

13

Pages :

e7066

Publisher :

Wiley Online Library

Publication date :

2024-03-26

ISSN :

2045-7634

English keyword(s) :

capecitabine
fluorouracil
genotype
high-throughput nucleotide sequencing
neoplasms
phenotype

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Introduction In April 2019, French authorities mandated dihydropyrimidine dehydrogenase (DPD) screening, specifically testing uracilemia, to mitigate the risk of toxicity associated with fluoropyrimidine-based chemotherapy. ...
Show more >Introduction In April 2019, French authorities mandated dihydropyrimidine dehydrogenase (DPD) screening, specifically testing uracilemia, to mitigate the risk of toxicity associated with fluoropyrimidine-based chemotherapy. However, this subject is still of debate as there is no consensus on a standardized DPD deficiency screening test. We conducted a real-life retrospective study with the aim of assessing the impact of DPD screening on the occurrence of severe toxicity and exploring the potential benefits of complete genotyping using next-generation sequencing. Methods All adult patients consecutively treated with 5-fluorouracil (5-FU) or its oral prodrug at six cancer centers between March 2018 and February 2019 were considered for inclusion. Dihydropyrimidine dehydrogenase deficiency screening included gene encoding DPD (DPYD) genotyping using complete genome sequencing and DPD phenotyping (uracilemia or dihydrouracilemia/uracilemia ratio) or both tests. Associations between each DPD screening method and (i) severe (grade ≥3) early toxicity and (ii) fluoropyrimidine dose reduction in the second chemotherapy cycle were evaluated using multivariable logistic regression analysis. Furthermore, we assessed the concordance between DPD genotype and phenotype using Cohen's kappa. Results A total of 551 patients were included. Most patients were tested for DPD deficiency (86%) including DPYD genotyping only (6%), DPD phenotyping only (8%), or both (72%). Complete DPD deficiency was not detected in the study population. Severe early toxicity events were observed in 73 patients (13%), with two patients (0.30%) presenting grade 5 toxicity. Despite the numerically higher toxicity rate in untested patients, the occurrence of severe toxicity was not significantly associated with the DPD screening method (p = 0.69). Concordance between the DPD genotype and phenotype was weak (Cohen's kappa of 0.14). Conclusion Due to insufficient numbers, our study was not able to demonstrate any added value of DPYD genotyping using complete genome sequencing to prevent 5-FU toxicity. The optimal strategy for DPD screening before fluoropyrimidine-based chemotherapy requires further clinical evaluation.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
CHU Lille
Institut Pasteur de Lille

Collections :

• IMPact de l'Environnement Chimique sur la Santé humaine (IMPECS) - ULR 4483

Submission date :

2024-05-06T21:19:02Z
2024-06-12T07:30:19Z