Introduction UGT1A1 poor metabolisers (PMs) are at higher risk of severe irinotecan-related toxicity. A 30% upfront dose reduction is commonly recommended for safety, but whether this compromises survival has remained uncertain.
Introduction
UGT1A1 poor metabolisers (PMs) are at higher risk of severe irinotecan-related toxicity. A 30% upfront dose reduction is commonly recommended for safety, but whether this compromises survival has remained uncertain.
Summary
In this Dutch multicentre retrospective cohort (2017–2024), including 779 patients with colorectal or pancreatic cancer, 9.8% were UGT1A1 poor metabolisers who received a 30% reduced irinotecan dose. Progression-free and overall survival were comparable between dose-reduced PMs and fully dosed intermediate/normal metabolisers. Severe toxicity rates were also similar. These findings suggest that genotype-guided dose reduction improves safety without compromising survival, supporting routine UGT1A1-guided irinotecan dosing in clinical practice.
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