Dihydropyrimidine dehydrogenase (DPD) deficient patients are at an increased risk of severe fluoropyrimidine (5-fluorouracil or capecitabine, FP) toxicity, which can sometimes be fatal. Large international studies have demonstrated that routine DPYD gene testing is both feasible and cost effective, however is not currently a standard of care in Australia for patients planned to commence FP-based therapy. This analysis aimed to assess the feasibility of establishing a pharmacist-led DPYD gene testing service, as developed overseas, in an Australian tertiary/quarternary cancer centre.
Medical oncology consultants, nurse consultants, pathology department and pharmacists were engaged to develop a site-specific DPYD gene testing protocol. Patients planned for FP therapy, without previous FP exposure, were referred to the clinical pharmacogenetics pharmacist, before a blood or buccal swab sample was taken. An external genomics company screened for the five Clinical Pharmacogenetics Implementation Consortium (CPIC) recommended gene variants (c.1905+1G>A, c.1679T>G, c.2846A>T, c.1236G>A and c.557A>G). Dose recommendations based on CPIC guidelines and phenotype were made to the treating clinician. Patients were followed-up for toxicity (graded according to CTCAE v5.0) at 3-5 days post first FP exposure and pre-cycle 2 commencement.
From 16th December 2019 to 15th July 2020, 188 patients (median age 59 years, 53% female) were planned for FP therapy. Genomic testing did not occur for twelve patients and were excluded. Median time from samples being taken to results becoming available was seven days. 95% (167 of 176 patients) of results were available prior to the planned cycle 1 chemotherapy commencement date. Nine patients experienced at least one grade 3/4 toxicity prior to cycle 2; all had normal metaboliser phenotypes. Six patients with intermediate metaboliser phenotypes and one patient with poor metaboliser phenotype were identified.
A pharmacist-led DPYD gene testing service is feasible and can be readily embedded into an Australian health service.