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Journal of Dental and Health Sciences

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Pharmacogenomics in Pediatric Cancer Patients Treated with Irinotecan: A Systematic Review

Volume 1, Issue 4 - 2025

Review Article

Nisarga P, Ramdas Bhat, Sinchana S Bhat

Received: 2025-07-07

Accepted: 2025-09-25

Published: 2025-10-01

DOI: 10.63150/osjdhs.2025.26

Pages: 244-258

Abstract

Background: Irinotecan, a vital chemotherapeutic in pediatric oncology, often causes severe toxicities, including grade 3-4 neutropenia and diarrhoea. These adverse events are strongly linked to interpatient variability in the metabolism of its active metabolite, SN-38, primarily by the UDP-glucuronosyltransferase 1A1 (UGT1A1) enzyme. Polymorphisms like UGT1A1*28 and *6 impair this detoxification, increasing toxicity risk. While UGT1A1 genotyping is standard for adults, pediatric-specific guidelines are lacking due to developmental differences in enzyme expression and pharmacokinetics.

Objective: This systematic review aims to synthesize evidence on UGT1A1 pharmacogenomics in pediatric cancer patients receiving irinotecan, focusing on genotype-toxicity associations, implementation challenges, and research gaps.

Methods: Following PRISMA guidelines, we searched PubMed, Scopus, and EMBASE (January 2000 – August 2025). Included studies involved pediatric patients (<18 years) with irinotecan treatment, reporting UGT1A1 genotypes and their association with grade 3-4 neutropenia or diarrhoea. Data were narratively synthesized, and study quality assessed.

Results: Twenty-six studies (n=2,158 pediatric patients) consistently confirmed that UGT1A1*28 and *6 polymorphisms significantly increase the risk of severe neutropenia and diarrhoea (ORs typically 2.5-4.5). Genotype effects were attenuated in younger children (<5 years) due to developmental variations in UGT1A1 expression. Implementation barriers included testing cost, limited pediatric guidelines, and clinician unfamiliarity.

Conclusion: UGT1A1 polymorphisms are strong predictors of severe irinotecan toxicity in pediatric cancer patients. Pretherapeutic genotyping offers significant potential for personalized dosing and toxicity reduction. Urgent development of age-stratified guidelines and addressing implementation challenges are crucial for advancing precision medicine in pediatric oncology.

Keywords: UGT1A1, pharmacogenomics, irinotecan, pediatric oncology, personalized medicine, genotype-guided dosing, systematic review

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