Dutch pharmacogenetics working group (DPWG) guideline for the gene-drug interaction between UGT1A1 and irinotecan

The Dutch Pharmacogenetics Working Group (DPWG) aims to facilitate PGx implementation by developing evidence-based pharmacogenetics guidelines to optimize pharmacotherapy. This guideline describes the starting dose optimization of the anti-cancer drug irinotecan to decrease the risk of severe toxicity, such as (febrile) neutropenia or diarrhoea. Uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1 encoded by the UGT1A1 gene) enzyme deficiency increases risk of irinotecan-induced toxicity. Gene variants leading to UGT1A1 enzyme deficiency (e.g. UGT1A1*6, *28 and *37) can be used to optimize an individual's starting dose thereby preventing carriers from toxicity. Homozygous or compound heterozygous carriers of these allele variants are defined as UGT1A1 poor metabolisers (PM). DPWG recommends a 70% starting dose in PM patients and no dose reduction in IM patients who start treatment with irinotecan. Based on the DPWG clinical implication score, UGT1A1 genotyping is considered essential, indicating that UGT1A1 testing must be performed prior to initiating irinotecan treatment.

Automated summary

The Dutch Pharmacogenetics Working Group has developed evidence-based guidelines for the optimal starting dose of the anti-cancer drug irinotecan, based on UGT1A1 gene variants. UGT1A1 genotyping is considered essential prior to initiating irinotecan treatment to decrease the risk of severe toxicity.