Loading
A one-off blood test done before fluorouracil or capecitabine that finds the roughly one in twenty-five people who break the drug down too slowly. Lowering their starting dose reduces severe and occasionally fatal toxicity, and in the one matched comparison published so far survival was not shortened overall.
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) lowered the starting dose in the 85 carriers it found. Severe toxicity was still commoner in carriers than in non-carriers (39 against 23 per cent), but for DPYD*2A carriers the relative risk fell from 2.87 in a historical full-dose cohort to 1.31, and the authors wrote that a larger reduction for two of the four variants requires investigation. A matched analysis of the same programme (Journal of Clinical Oncology 2023) found no shortening of progression-free or overall survival in carriers taken together, with shorter progression-free survival in c.1236G>A carriers, and called itself exploratory. 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 the FDA announced on 5 February 2026 that the capecitabine and fluorouracil labels had been revised: the boxed warning now advises DPYD testing before treatment unless immediate treatment is necessary.
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 Pharmacokinetics (PK), half-life and exposure, Dose reduction, interruption and discontinuation, Head and neck squamous cell carcinoma, Breast cancer (all types) and the tag precision.
Shares Fluorouracil dosing by measured blood level, Pharmacokinetics (PK), half-life and exposure and the tag precision.
Shares Dose reduction, interruption and discontinuation, Oesophageal and junctional adenocarcinoma, Gastric & gastro-oesophageal junction cancer, Head and neck squamous cell carcinoma and the tag precision.
Shares Dose reduction, interruption and discontinuation, Breast cancer (all types), Colorectal cancer and the tag precision.
Shares Pharmacokinetics (PK), half-life and exposure, Dose reduction, interruption and discontinuation, Precision roadmap: margins measured in millimetres → tests that find a target → doses fitted to the person → precision that changes outcomes and the tag precision.
Shares Precision roadmap: margins measured in millimetres → tests that find a target → doses fitted to the person → precision that changes outcomes, Breast cancer (all types) and the tag precision.
Shares Companion diagnostics, Germline (hereditary) testing, Gastric & gastro-oesophageal junction cancer, Pancreatic ductal adenocarcinoma and the tag precision.
Shares Companion diagnostics, Pancreatic ductal adenocarcinoma, Colorectal cancer and the tag precision.
Every source this page cites, grouped by who published it. Grouping is read from the web address, not assigned by hand.
A source that has moved or gone is reported by the weekly link check. /audit/