ArticleClinical pharmacokinetics2023
Irinotecan-Induced Toxicity: A Pharmacogenetic Study Beyond UGT1A1.
Article in Clinical pharmacokinetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- Meta-analysis revisiting the influence ofPharmacogenomics · 2024Pooled it
- Identification of low-toxicity DNA topoisomerase I inhibitors with potential blood-brain barrier penetrability for glioblastoma therapy: structure-based virtual screening reveals promising novel Scaffolds.Molecular diversity · 2026Article
- Thapsigargin enhanced chemotherapeutic sensitivity of irinotecan in the inflammation-induced colorectal cancer model in mice.Scientific reports · 2026Article
- Distinct safety profiles of liposomal and conventional irinotecan: insights from clinical experience and real-world data.Frontiers in pharmacology · 2026Article
- Personalizing cancer therapy: the role of pharmacogenetics in overcoming drug resistance and toxicity.Molecular biology reports · 2025Review
- Spectroscopic and molecular docking studies on binding interactions of camptothecin drugs with bovine serum albumin.Scientific reports · 2025Article
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- Allele frequency of genetic variations related to theJournal of diabetes and metabolic disorders · 2024Article
- Regulation of carboxylesterases and its impact on pharmacokinetics and pharmacodynamics: an up-to-date review.Expert opinion on drug metabolism & toxicology · 2024Review
- Machine learning in onco-pharmacogenomics: a path to precision medicine with many challenges.Frontiers in pharmacology · 2023Review
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectiveSide 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.
methodsPatients 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.
resultsFrom 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).
conclusionOur study indicates that ABCG2 and CES1 SNPs might be used as predictive markers for irinotecan-induced toxicity.
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