Loading
A one-off blood test done before fluorouracil or capecitabine that finds the roughly one in twenty-five people who cannot break the drug down; halving their dose prevents severe and occasionally fatal toxicity without losing effect.
What it measures. Fluorouracil and its oral prodrug capecitabine are cleared by dihydropyrimidine dehydrogenase (DPD), encoded by the DPYD gene. About three to eight per cent of Europeans carry one of four well-characterised variants (DPYD*2A, *13, c.2846A>T, HapB3) that halve enzyme activity; very rare people carry two and have no enzyme at all. Genotyping reads these variants from blood or saliva. France and some other countries instead or additionally measure plasma uracil, the enzyme's natural substrate, which rises when DPD is deficient whatever the genetic cause (phenotyping).
Evidence and guidelines. A prospective Dutch study of 1,103 patients (Lancet Oncology 2018) showed that reducing the starting dose in carriers cut severe toxicity to the level seen in non-carriers, and pharmacokinetic work showed exposure matched a normal dose. The Clinical Pharmacogenetics Implementation Consortium publishes the dose table: a 50 per cent starting dose reduction for heterozygous carriers and avoidance for homozygous or compound heterozygous patients, with the option to escalate on tolerance. In 2020 the European Medicines Agency recommended DPD testing before all fluoropyrimidine treatment; NHS England commissioned genotyping the same year, and most European countries followed. In the United States testing is recommended by several bodies and the drug labels warn of the risk, but it is not yet universal.
Who should have it and what changes. Everyone about to start fluorouracil, capecitabine or tegafur, whatever the cancer. A normal result changes nothing. A carrier result lowers the starting dose, with careful escalation if tolerated; a complete deficiency means choosing a different drug. The test costs tens of pounds, comes back in a few days to a week, and needs doing once in a lifetime. The main gaps are variants common in non-European populations that the standard four-variant panel misses, and delays when the result is not back before cycle one.
Targeted genotyping of DPYD variants that reduce dihydropyrimidine dehydrogenase activity, translated by consortium tables into an activity score and starting dose, optionally supplemented by plasma uracil measurement.
Query for this technology: (TITLE:"DPYD genotyping and DPD phenotyping before fluoropyrimidines" OR ABSTRACT:"DPYD genotyping and DPD phenotyping before fluoropyrimidines" OR TITLE:"DPYD testing" OR ABSTRACT:"DPYD testing" OR TITLE:"DPD deficiency testing" OR ABSTRACT:"DPD deficiency testing" OR TITLE:"dihydropyrimidine dehydrogenase test" OR ABSTRACT:"dihydropyrimidine dehydrogenase test") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about DPYD genotyping and DPD phenotyping before fluoropyrimidines, not a curated reading list.
Shares Mucositis and stomatitis, Hand-foot syndrome and hand-foot skin reaction, Neutropenia, Capecitabine.
Shares Mucositis and stomatitis, Hand-foot syndrome and hand-foot skin reaction, Neutropenia, Pancreatic ductal adenocarcinoma.
Shares Hand-foot syndrome and hand-foot skin reaction, Dose reduction, interruption and discontinuation, Colorectal cancer.
Shares Oesophageal and junctional adenocarcinoma, Fluorouracil (5-FU), Capecitabine, Gastric & gastro-oesophageal junction cancer.
Shares Oesophageal and junctional adenocarcinoma, Gastric & gastro-oesophageal junction cancer, Pancreatic ductal adenocarcinoma, Colorectal cancer.
Shares Oesophageal and junctional adenocarcinoma, Gastric & gastro-oesophageal junction cancer, Breast cancer (all types), Colorectal cancer.
Shares Anal cancer (squamous cell carcinoma), Gastric & gastro-oesophageal junction cancer, Breast cancer (all types), Colorectal cancer.
Shares Oesophageal and junctional adenocarcinoma, Gastric & gastro-oesophageal junction cancer, Breast cancer (all types), Colorectal cancer.