Aims: While fluoropyrimidine (FP) toxicities related to dihydropyrimidine dehydrogenase (DPD) deficiency are well documented globally, the impact of these enzymatic aberrations have not been explored extensively in the Australian hospital setting. In this preliminary investigation, we aimed to study the prevalence of FP toxicities in patients receiving FP-based treatment at a tertiary Australian hospital.

Methods: We conducted a retrospective audit of all patients over 18 years of age who received their first dose of fluorouracil or capecitabine at the Gold Coast University Hospital between 1st January and 31st December 2020. The electronic medical record of each patient was analysed for known FP toxicities and details of adverse events (AEs) were recorded, including severity according to the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Subsequent management including changes or delays to the chemotherapy regimen were also investigated.

Results: A total of 215 patients were included in this study: 107 patients received fluorouracil and 108 patients received capecitabine. A total of 1083 AEs were reported. The most frequently reported toxicities in order of decreasing prevalence were fatigue (233 AEs; 21.5%), diarrhoea (164 AEs; 15.1%) nausea (157 AEs; 14.5%), hand and foot syndrome (89 AEs; 8.2%), mucositis (78 AEs; 7.2%) and neutropenia (44 AEs; 4%). The most severe toxicities (grades 3 or 4) were neutropenia (34 AEs; 3.1%), diarrhoea (23 AEs; 2.1%), nausea (8 AEs; 0.7%) and chest pain (3 AEs; 0.3%). Treatment delays occurred in 62 instances, dose reduction occurred in 47 instances and cessation of therapy occurred in 47 instances.

Conclusion: In Australia, toxicities from FP are common and can be of extreme severity. Adverse events may result in treatment delays and early cessation of therapy, potentially impacting clinical efficacy and quality of life. Further research is planned to investigate the relationship between DPD deficiencies and FP toxicities.