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Pharmacogenetic and clinical predictors of ondansetron failure in a diverse pediatric oncology population

Shana S Jacobs1,2, Jeffrey S Dome3,4, Jiaxiang Gai5

  • 1Division of Oncology, Children's National Hospital, Washington, DC, USA. ssjacobs@childrensnational.org.

Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer
|January 12, 2022
PubMed
Abstract

Insights

Genetic variations in 5-HT3RB and ABCB1, along with age and BMI, can predict ondansetron failure in pediatric cancer patients. This helps identify individuals at higher risk for chemotherapy-induced nausea and vomiting (CINV).

Area of Science:

  • Pharmacogenomics
  • Oncology
  • Genetics

Background:

  • Chemotherapy-induced nausea and vomiting (CINV) is a significant adverse event in cancer therapy.
  • Ondansetron, a 5-HT3 receptor antagonist, is commonly used but fails in up to 30% of patients.
  • Identifying predictors of ondansetron failure is crucial for improving patient care.

Purpose of the Study:

  • To investigate the association between genetic variations in drug-metabolizing enzymes (CYP2D6), transporters (ABCB1), and receptors (5-HT3) with ondansetron failure.
  • To explore the role of patient demographics such as age and BMI in predicting ondansetron failure.

Main Methods:

  • DNA was extracted from blood samples of pediatric oncology patients.
  • Genotyping was performed for specific variants in ABCB1, 5-HT3RB, and CYP2D6 genes.
  • Ondansetron failure was assessed using medical records and patient-reported outcomes (PROs).

Main Results:

  • A significant association was found between the 5-HT3RB variant rs45460698 and ondansetron failure (p=0.0281, OR 2.67).
  • Age (especially >12 years) and higher BMI were predictive of ondansetron failure.
  • In multivariate analysis, age >12 years was a strong predictor (OR 7.108, p=0.0008).

Conclusions:

  • Specific genetic variants in 5-HT3RB and ABCB1, along with age and BMI, can help predict the risk of ondansetron failure.
  • These factors are valuable in identifying pediatric oncology patients at increased risk for CINV.
  • Personalized approaches based on genetic and demographic factors may improve CINV management.
Keywords:
Chemotherapy-induced nauseaOndansetronPediatric cancerPharmacogenomics

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