Related Experiment Video
Updated: Jun 13, 2026

Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform
Published on: May 10, 2024
Real-World Impact of UGT1A1 Genotype-Guided Irinotecan Dosing on Severe Toxicity and Hospitalization: A Multicenter
Niels Heersche1,2, Sofía L J Peeters3,4, Doortje Böhm3,4
11Department of Medical Oncology, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands.
Background:
Risk of irinotecan-related severe toxicity is significantly higher in patients carrying 2 dysfunctional UGT1A1 gene variants, characterized as poor metabolizers (PMs), following standard irinotecan dosing. Since 2020, we implemented UGT1A1 genotype-guided dosing of irinotecan in routine clinical practice to reduce toxicity in PMs. This study evaluates its impact on severe toxicity in a real-world cohort.
Patients And Methods:
Our study cohort included adult patients who received UGT1A1 genotype-guided irinotecan dosing at 6 Dutch hospitals between December 2020 and April 2024. Patients were included in the primary analysis if irinotecan was dosed according to UGT1A1 genotype (ie, 100% ±10% dose intensity for intermediate and normal metabolizers [IM/NMs] and 70% ±10% for PMs) in at least cycle 1. Toxicities, hospitalizations, and treatment alterations were collected for cycles 1-3 and graded according to CTCAE version 5.0. Endpoints were compared between PMs with a 70% starting dose and fully dosed IM/NMs.
Results:
A total of 501 patients were included in the primary analysis; 54 of whom were PMs (10.8%). Baseline characteristics were evenly distributed between groups. The incidences of overall severe toxicity (29.6% vs 34.0%; P=.52), febrile neutropenia (3.7% vs 5.8%; P=.76), severe neutropenia (17.0% vs 17.8%; P=.88), severe diarrhea (13.0% vs 15.0%; P=.69), and toxicity-related hospitalization (14.8% vs 21.7%; P=.24) were comparable between dose-reduced PMs and fully dosed IM/NMs. In a secondary analysis, 9 UGT1A1 PMs who received an unintended full irinotecan dose experienced more severe toxicity than PMs with a 70% starting dose (overall severe toxicity: 77.8% vs 29.6%; P=.009).
Conclusions:
UGT1A1 genotype-guided dosing of irinotecan improves patient safety and treatment tolerability of irinotecan. A 70% starting dose of irinotecan for UGT1A1 PMs is necessary to normalize the risk of severe toxicity to that of IM/NMs.
Related Concept Videos
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Drug toxicity: Idiosyncratic Reactions
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Drug Accumulation During Multiple Dosing: Intermittent IV Infusions
Drug Toxicity: Risk factors