Dataset Information

Potential added value of combined DPYD/DPD genotyping and phenotyping to prevent severe toxicity in patients with a DPYD variant and decreased dihydropyrimidine dehydrogenase enzyme activity.

ABSTRACT:

Objective

To investigate if dihydropyrimidine dehydrogenase phenotyping has added value when combined with DPYD genotyping in predicting fluoropyrimidine-related toxicity.

Methods

Retrospective cohort study in which treatment and toxicity data were collected of 228 patients genotyped for four DPYD variants and phenotyped using an ex vivo peripheral blood mononuclear cell assay.

Results

Severe toxicity occurred in 25% of patients with a variant and normal dihydropyrimidine dehydrogenase activity, in 21% of patients without a variant and with decreased dihydropyrimidine dehydrogenase activity, and in 29% of patients without a variant and with normal dihydropyrimidine dehydrogenase activity (controls). The majority of patients with a variant or a decreased dihydropyrimidine dehydrogenase activity received an initial dose reduction (68% and 53% vs 19% in controls) and had a lower mean dose intensity (75% and 81% vs 91% in controls). Fifty percent of patients with a variant and decreased enzyme activity experienced severe toxicity, despite the lowest initial dose and whole treatment dose intensity. They also experienced more grade 4/5 toxicities.

Conclusions

Our results indicate that a combined genotype-phenotype approach could be useful to identify patients at increased risk for fluoropyrimidine-associated toxicity (e.g. patients with a variant and decreased dihydropyrimidine dehydrogenase activity). Because the group sizes are too small to demonstrate statistically significant differences, this warrants further research in a prospective study in a larger cohort.

SUBMITTER: Ockeloen CW

PROVIDER: S-EPMC9749565 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Publications

Potential added value of combined DPYD/DPD genotyping and phenotyping to prevent severe toxicity in patients with a <i>DPYD</i> variant and decreased dihydropyrimidine dehydrogenase enzyme activity.

Ockeloen Charlotte W CW Raaijmakers Aron A Hijmans-van der Vegt Manon M Bierau Jörgen J de Vos-Geelen Judith J Willemsen Annelieke Ecab AE van den Bosch Bianca Jc BJ Coenen Marieke Jh MJ

Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners 20211119 1

<h4>Objective</h4>To investigate if dihydropyrimidine dehydrogenase phenotyping has added value when combined with <i>DPYD</i> genotyping in predicting fluoropyrimidine-related toxicity.<h4>Methods</h4>Retrospective cohort study in which treatment and toxicity data were collected of 228 patients genotyped for four <i>DPYD</i> variants and phenotyped using an <i>ex vivo</i> peripheral blood mononuclear cell assay.<h4>Results</h4>Severe toxicity occurred in 25% of patients with a variant and norma ...[more]

PMID: 34797200

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