Pharmacogenetic and clinical predictors of ondansetron failure in a diverse pediatric oncology population.
Support Care Cancer
; 30(4): 3513-3520, 2022 Apr.
Article
em En
| MEDLINE
| ID: mdl-35018520
ABSTRACT
PURPOSE:
Chemotherapy-induced nausea and vomiting (CINV) is a frequently seen burdensome adverse event of cancer therapy. The 5-HT3 receptor antagonist ondansetron has improved the rates of CINV but, unfortunately, up to 30% of patients do not obtain satisfactory control. This study examined whether genetic variations in a relevant drug-metabolizing enzyme (CYP2D6), transporter (ABCB1), or receptor (5-HT3) were associated with ondansetron failure.METHODS:
DNA was extracted from blood and used to genotype ABCB1 (3435C > T (rs1045642) and G2677A/T (rs2032582)), 5-HT3RB (rs3758987 T > C and rs45460698 (delAAG/dupAAG)), and CYP2D6 variants. Ondansetron failure was determined by review of the medical records and by patient-reported outcomes (PROs).RESULTS:
One hundred twenty-nine patients were approached; 103 consented. Participants were less than 1 to 33 years (mean 6.85). A total of 39.8% was female, 58.3% was White (22.3% Black, 19.4% other), and 24.3% was Hispanic. A majority had leukemia or lymphoma, and 41 (39.8%) met the definition of ondansetron failure. Of variants tested, rs45460698 independently showed a significant difference in risk of ondansetron failure between a mutant (any deletion) and normal allele (p = 0.0281, OR 2.67). Age and BMI were both predictive of ondansetron failure (age > 12 (OR 1.12, p = 0.0012) and higher BMI (OR 1.13, p = 0.0119)). In multivariate analysis, age > 12 was highly predictive of ondansetron failure (OR 7.108, p = 0.0008). rs45460698 was predictive when combined with an increased nausea phenotype variant of rs1045642 (OR 3.45, p = 0.0426).CONCLUSION:
Select phenotypes of 5-HT3RB and ABCB1, age, and potentially BMI can help predict increased risk for CINV in a diverse pediatric oncology population.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Antieméticos
/
Neoplasias
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Female
/
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article