Symptoms and signs
Patients with partial or complete DPD deficiency who are treated with a standard dose of fluoropyrimidine will have increased levels of the active metabolites of fluorouracil due to the reduce DPD activity. Increased levels of the fluorouracil active metabolite is associated with an increased risk of severe or even fatal toxicity.r
As a result patients will have typical fluoropyrimidine toxicity but this tends to appear much earlier and be more severe and prolonged. Patients who develop severe toxicity in the first few days of therapy should be considered likely to have DPD deficiency. An antidote is available for fluoropyrimidine overdose or overexposure and is highly effective if given within 96 hours. Read more about Fluoropyrimidine overdose or overexposure.
Investigations and diagnosis
There are two main tests for DPD deficiency – genotyping of DPYD or measuring the DPD phenotype (uracil and dihydrouracil blood levels).r
Genotyping of DPYD and DPD phenotype testing are available in Australia, however, they are currently not reimbursed and the cost and turnaround times may be limiting factors in testing upfront. The genotyping test is available through Douglas Hanley Moir Pathology (Sonic Pathology network) and is approximately $200 with a 1 - 2 week turnaround time. Preuracil and dihydrouracil levels are available through NSW Government Pathology. The current cost is $275 and turnaround time is unclear but expected to be a couple of weeks.
Currently no regulatory body - US Food and Drug Administration (FDA), European Medicines Agency (EMA) or Therapeutics Goods Administration (TGA) – or international guidelines – including European Society of Medical Oncology (ESMO) and National Comprehensive Cancer Network (NCCN) - require or recommend genetic testing prior to the administration of fluoropyrimidines.
Whilst the product information for both capecitabine and fluorouracil warn about the potentially fatal reactions attributed to DPD deficiency, it does not stipulate that genetic testing must be performed.