Risk of Toxicity From Topical 5-Fluorouracil Treatment in Patients Carrying DPYD Variant Alleles.
Clin Pharmacol Ther
; 115(3): 452-456, 2024 03.
Article
em En
| MEDLINE
| ID: mdl-38060335
ABSTRACT
Patients carrying DPYD variant alleles have increased risk of severe toxicity from systemic fluoropyrimidine chemotherapy. There is a paucity of data regarding risk of toxicity from topical 5-fluorouracil (5-FU) treatment in these patients, leading to inconsistent guideline recommendations for pretreatment testing and topical 5-FU dosing. The objective of this retrospective cohort study was to investigate whether DPYD variant allele carriers have increased risk of toxicity from topical 5-FU. Treatment and toxicity data were retrospectively abstracted from the electronic medical records. Genotypes for the five DPYD variants that are associated with increased toxicity from systemic fluoropyrimidine chemotherapy (DPYD*2A, DPYD*13, DPYD p.D949V, DPYD HapB3, and DPYD p.Y186C) were collected from a genetic data repository. Incidence of grade 3+ (primary end point) and 1+ (secondary end point) toxicity was compared between DPYD variant carriers vs. wild-type patients using Fisher's exact tests. The analysis included 201 patients, 7% (14/201) of whom carried a single DPYD variant allele. No patients carried two variant alleles or experienced grade 3+ toxicity. DPYD variant allele carriers did not have a significantly higher risk of grade 1+ toxicity (21.4% vs. 10.2%, odds ratio = 2.40, 95% confidence interval 0.10-2.53, P = 0.19). Given the low toxicity risk in patients carrying a single DPYD variant allele, there is limited potential clinical benefit of DPYD genetic testing prior to topical 5-FU. However, the risk of severe toxicity in patients with complete DPD deficiency remains unknown and topical 5-FU treatment should be avoided in these patients.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Di-Hidrouracila Desidrogenase (NADP)
/
Deficiência da Di-Hidropirimidina Desidrogenase
Limite:
Humans
Idioma:
En
Revista:
Clin Pharmacol Ther
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos