Introducing DPD Screening into Clinical Practice: The Sheffield Experience


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Alexander Burnett1,Alice Dewdney2
1Weston Park Hospital,2weston park hospital

Abstract

Background

Fluorouracil (5FU) forms the backbone of treatment for colorectal cancer (CRC). Dehydropyrimidine-dehydrogenease (DPD) breakdowns 5FU into inactive metabolites. Patients with DPD deficiency are at risk of severe toxicity. Genetic tests for DPD deficiency are commercially available but not routinely used in the UK. In Sheffield we trialled screening all new CRC patients prior to commencing 5FU; we report on the logistics of introducing a new screening program.

Method

Over three months all new CRC patients were offered screening using a multiparametric approach (genotyping and phenotyping).  Three blood samples were collected, two of which were put on dry ice within an hour, samples were sent to France for analysis twice a week. Results were available via an electronic portal.   We reviewed the results including time; between sample collection and result  and decision to treat to administration of chemotherapy. Data was collected from case notes, online portal and chemotherapy prescription system.

Results

DPD testing was offered to 66 patients, 55 results were received. No polymorphisms were demonstrated, however 3/55 (5%) were high-risk based on phenotype (dihydrouracil;uracil ratio). Of these; one had 100% dose before result available, one did not receive 5FU and the other had a significant dose reduction but developed grade 3 mucositis. Nine patients commenced chemotherapy before results available. The average wait for results;  15.7 days (range 4-43) and average time from decision-to-treat to administration of chemotherapy; 23.9 days (range 11-42).

Conclusion

There is clear evidence that screening for DPD deficiency potentially reduces toxicity. However, the introduction of a screening programme is not without challenges. Our results demonstrate that this methodology is not sustainable.  Results were slow and resulted in unacceptable delays in time to start treatment. Introduction must be carefully planned and implemented to ensure results are available upon in a timely manner without negatively impacting on treatment.