GENESCREEN: DPYD and UGT1A1 Genotyping for Fluoropyrimidine and Irinotecan dose personalisation to reduce severe toxicity

At least 4 DPYD and 3 UGT1A1 variants are associated with severe, potentially fatal, toxicity in patients treated with standard doses of FP/IRI requiring hospitalisation and costly resource utilisation. Identification of these variants is now standard practice in Europe leading to adjusted chemotherapy dosing to avoid severe toxicity and its economic burden, without compromising anti-tumour effects. Australia has not yet implemented pharmacogenomics (PGx) guided dosing due to a lack of evidence on feasibility, clinical efficacy in an Australian context, and cost-effectiveness.

GENESCREEN aims to address these gaps, providing prospective clinical evidence on feasibility of implementing DPYD/UGT1A1 testing routinely, its clinical efficacy/impact and cost-effectiveness. In addition to providing the evidence to support a Medical Services Advisory Committee (MSAC) submission for Medicare rebates for this testing, this program will facilitate updated clinical practice guidelines, and identify other variants in DPYD/UGT1A1 to implement in a comprehensive program to increase sensitivity of PGx guided dosing.