Irinotecan-Induced Toxicity: A Pharmacogenetic Study Beyond UGT1A1.
Clin Pharmacokinet
; 62(11): 1589-1597, 2023 11.
Article
em En
| MEDLINE
| ID: mdl-37715926
ABSTRACT
BACKGROUND AND OBJECTIVE:
Side effects of irinotecan treatment can be dose limiting and may impair quality of life. In this study, we investigated the correlation between single nucleotide polymorphisms (SNPs) in genes encoding enzymes involved in the irinotecan metabolism and transport, outside UGT1A1, and irinotecan-related toxicity. We focused on carboxylesterases, which are involved in formation of the active metabolite SN-38 and on drug transporters.METHODS:
Patients who provided written informed consent at the Erasmus Medical Center Cancer Institute to the Code Geno study (local protocol MEC02-1002) or the IRI28-study (NTR-6612) were enrolled in the study and were genotyped for 15 SNPs in the genes CES1, CES2, SLCO1B1, ABCB1, ABCC2, and ABCG2.RESULTS:
From 299 evaluable patients, 86 patients (28.8%) developed severe irinotecan-related toxicity. A significantly higher risk of toxicity was seen in ABCG2 c.421C>A variant allele carriers (P = 0.030, OR 1.88, 95% CI 1.06-3.34). Higher age was associated with all grade diarrhea (P = 0.041, OR 1.03, 95% CI 1.00-1.06). In addition, CES1 c.1165-41C>T and CES1 n.95346T>C variant allele carriers had a lower risk of all-grade thrombocytopenia (P = 0.024, OR 0.42, 95% CI 0.20-0.90 and P = 0.018, OR 0.23, 95% CI 0.08-0.79, respectively).CONCLUSION:
Our study indicates that ABCG2 and CES1 SNPs might be used as predictive markers for irinotecan-induced toxicity.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
3_ND
/
4_TD
/
8_ODS3_consumo_sustancias_psicoactivas
Base de dados:
MEDLINE
Assunto principal:
Camptotecina
/
Antineoplásicos Fitogênicos
Tipo de estudo:
Guideline
/
Prognostic_studies
Aspecto:
Patient_preference
Limite:
Humans
Idioma:
En
Revista:
Clin Pharmacokinet
Ano de publicação:
2023
Tipo de documento:
Article