Background: Approximately 10,000 Australian patients are prescribed Fluoropyrimidine (FP) chemotherapy annually for colorectal, gastrointestinal, breast and head and neck cancers. Severe toxicity, hospitalisation and death can result from dihydropyrimidine dehydrogenase (DPD) deficiency, the critical enzyme driving FP metabolism. Genotyping of DPYD, the gene encoding DPD, can identify patients who carry well-known functionally significant variants (c.1905+1G>A, c.1679T>G, c.2846A>T and c.1236G>A) ahead of treatment to allow dose adjustments to improve FP tolerability. This screening model also shows cost effectiveness in Europe.
Aims: GeneScreen 5-FU is a feasibility study (n=50) that will:
Methods: Cancer patients ≥ 18 years old who are undertaking FP chemotherapy are eligible. Blood samples are genotyped by real-time PCR (validated by Sanger Sequence PCR), and results returned to oncologists for dose adjustment at clinician discretion. Questionnaire data collected from health care providers and patients explores perceived barriers and enablers for DPYD testing in Australia.
Results: GeneScreen 5-FU is currently recruiting at 2 sites, with another 2 commencing imminently. 19 patients have been recruited, with 2 variant carriers identified. 12 questionnaires have been completed. Recruitment is projected to hit our target by last august and data analysis is projected for September.
Conclusions: This study will determine the local feasibility of DPYD genotyping for larger-scale implementation. The larger-scale programme will be the first pharmacogenomic study in Australian adult oncology patients, incorporating a health economic analysis. Our ultimate goal is to provide an equitable and accessible DPYD genotyping service to all Australian cancer patients, to reduce the burden of toxicity on patients and the associated financial burden on the Australian health care system on par with models already implemented in Europe and the UK.