• Dr Antti Hosio

CV

Dr Antti Hosio, MD, is a  Clinical Oncologist at the Comprehensive Cancer Centre of Helsinki University Hospital, where his main interest is in pharmacotherapies of gastrointestinal cancers and palliative medicine. Dr Hosio has participated in several clinical trials aiming to develop treatment options for colorectal cancer patients. Hosio is a Doctoral researcher in the Pharmacogenetics research group at the University of Helsinki.

ABSTRACT

Implementing DPYD genotyping in Finland: impact on fluoropyrimidine exposure and safety

Fluoropyrimidines 5-fluorouracil, capecitabine, and tegafur are commonly used anti-cancer drugs in the treatment of various solid tumors. Historically, severe toxicities have occurred in up to 30% of patients receiving 5-fluorouracil or capecitabine and have led to fatalities in 0.5-2% of patients. An important cause of toxicity is reduced dihydropyrimidine dehydrogenase (DPD) enzyme activity accounting for up to 50-75% of the severe fluoropyrimidine toxicities and most of the lethal toxicities. Variations in the DPYD gene, encoding DPD, determine enzyme activity and might increase the risk for drug accumulation and toxic effects. Pre-emptive testing of DPYD variants followed by genotype-guided dose adjustments reduce fluoropyrimidine-related toxicities and subsequent hospitalization while being cost-effective. The Clinical Pharmacogenetics Implementation Consortium has published guidelines for fluoropyrimidine dose modification for genetically intermediate or poor DPD metabolizers. The European Medicines Agency recommends testing for DPD deficiency, and in Finland, pre-emptive DPYD genotyping has been part of standard care in the treatment of fluoropyrimidine-receiving patients since 2019. An observational clinical trial investigating the impact of implementing DPYD genotype testing into routine practice in Finnish breast and colorectal cancer patients has been carried out in Finnish cancer centres since 2019. Results from this study will be presented.