Real-World Impact of UGT1A1 Genotype-Guided Irinotecan Dosing on Severe Toxicity and Hospitalization: A Multicenter Study
Abstract
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…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 501 participants or records.
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