Title : DPD mutation testing prior to administration of systemic fluoropyrimidine chemotherapy for cancer treatment.
Abstract:
Background
Fluoropyrimidine based-drugs, such as capecitabine and 5-fluorouracil, are used to treat a variety of cancers.1 Deficiency of dihydropyrimidine dehydrogenase (DPD), an enzyme that catabolises fluoropyrimidines, significantly increases risk of drug toxicity1, therefore dose alteration is recommended.2 Prevalence of DPD deficiency is disputed, but initial estimates suggest 3-5%.3 Guidance from UK Chemotherapy Board (UKCB) recommends that all patients should have a DPD test prior to fluoropyrimidine treatment.4
Methods
All patients who receive a first dose of either capecitabine or 5-fluorouracil for systemic cancer treatment between 1st May and 31st August 2022 at Queen Elizabeth Hospital Birmingham (QEHB) have been retrospectively audited (n=163). Data collection and analysis includes: first dose date, DPD testing date and results, first dose alterations and delays awaiting results.
Results
Average time from patient sampling to result reporting was 7.0 days. 9.2% of patients did not have a result available prior to first dose, with 4.9% having no test at all. Despite test results being unavailable, 100% of these patients proceeded with treatment without delay. 6.7% of patients without timely testing subsequently had mutations detected after treatment had been initiated.
Conclusion
Compliance with the UKCB guideline appears poor, with many potential factors influencing this. Therefore, there is a risk of toxicity present which is easily preventable. Findings from this hospital are widely relevant to other oncology centres and emphasise the importance of improving DPD test rates in accordance with national guidance to improve patient care. Various techniques, such as automated reminders for testing when prescribing, may be advantageous for service improvement.
