{"entity":{"id":"idea-tr1-pre-emptive-pharmacogenomic-testing","kind":"idea","name":"Test DPYD, UGT1A1 and TPMT/NUDT15 before the first dose, everywhere","aka":[],"tldr":"A cheap gene test for DPYD, UGT1A1 and TPMT or NUDT15 before fluoropyrimidines, irinotecan or thiopurines identifies people at risk of severe or fatal toxicity so their dose can be lowered. The EMA has recommended DPD testing since 2020; US uptake remains partial.","summary":"Mandatory pre-treatment genotyping for DPYD variants before fluoropyrimidines, UGT1A1*28 and *6 before irinotecan, and TPMT/NUDT15 before thiopurines, with genotype-guided dose reduction per CPIC guidelines, reimbursed and built into chemotherapy order sets. The EMA recommended DPD testing in 2020 and a prospective Dutch study showed genotype-guided dosing reduced severe toxicity; US uptake remains partial.","asOf":"2026-09-08","links":[{"label":"Henricks et al., DPYD genotype-guided dose individualisation of fluoropyrimidine therapy: a prospective safety analysis (Lancet Oncol 2018)","url":"https://doi.org/10.1016/S1470-2045(18)30686-7"},{"label":"Glewis et al., Toxicity and treatment outcomes with pharmacogenetic-guided dosing compared to standard BSA-based fluoropyrimidine dosing: systematic review and meta-analysis (Br J Cancer 2022)","url":"https://doi.org/10.1038/s41416-022-01779-6"},{"label":"Shaunak et al., Implementation of mass pharmacogenetic testing: DPD testing prior to fluoropyrimidine treatment (Br J Clin Pharmacol 2025)","url":"https://doi.org/10.1002/bcp.70057"},{"label":"El Rouby et al., Global Investigation of Clinical Implementation Strategies for DPYD Testing (Clin Transl Sci 2026)","url":"https://doi.org/10.1111/cts.70466"},{"label":"CPIC guideline: fluoropyrimidines and DPYD","url":"https://cpicpgx.org/guidelines/guideline-for-fluoropyrimidines-and-dpyd/"},{"label":"EMA: fluorouracil and related substances (DPD testing)","url":"https://www.ema.europa.eu/en/medicines/human/referrals/fluorouracil-fluorouracil-related-substances-capecitabine-tegafur-flucytosine-containing-medicinal-products"}],"tags":["protocol-upgrade","upgrade:proven-unevenly-used","evidence:strong","precision"],"related":[],"cancers":["colorectal","gastric","pancreatic"],"sections":[],"technologies":["dpyd-genotyping","oncology-pharmacogenomics","cytotoxic-chemotherapy","germline-testing","topoisomerase-inhibitors"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-dose-optimisation","b-toxicity-qol"],"keyPapers":["paper-henricks-lancet-oncol"],"journals":[],"dependsOn":[],"notes":["Protocol upgrade, graded proven but unevenly used, on the DPYD evidence. In 17 Dutch hospitals, 85 of 1,103 evaluable patients (8 per cent) carried one of four DPYD variants; with genotype-guided dose reduction the relative risk of severe toxicity in DPYD*2A carriers was 1.31, against 2.87 in a historical cohort given full doses (Henricks, 2018). A 2022 meta-analysis of 17 studies found pharmacogenetics-guided dosing reduced grade 3 or 4 toxicity (risk ratio 0.32, 95 per cent confidence interval 0.27 to 0.39) with no difference in response (Glewis, 2022).","Adoption gap, as measured: in a 2021 survey after NHS England commissioned the test, 131 of 138 United Kingdom organisations (94.9 per cent) reported testing all patients receiving fluoropyrimidines, with turnaround from under 2 days to more than 10 (Shaunak, 2025). Across 28 sites in 9 countries in the Pharmacogenomics Global Research Network, only 2 reported testing more than 75 per cent of patients due a fluoropyrimidine, 70 per cent relied on clinicians remembering to order the test, and median turnaround was 10 days (El Rouby, 2026)."],"hypothesis":"Universal pre-emptive genotyping with guided dosing will reduce severe fluoropyrimidine toxicity by more than half among variant carriers and reduce toxicity-related hospitalisations at population level without reducing efficacy.","rationale":"The evidence for DPYD is prospective and the test is inexpensive; the barrier is implementation and reimbursement, not science.","test":"Implementation trial across a health system: order-set-integrated genotyping versus usual care, with severe toxicity and hospitalisation as outcomes and cost-effectiveness analysis.","maturity":"being-tested-at-scale","actor":"payer","cost":"small","horizonYears":2},"route":"/ideas/idea-tr1-pre-emptive-pharmacogenomic-testing/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"dpyd-genotyping","kind":"technology","name":"DPYD genotyping and DPD phenotyping before fluoropyrimidines","route":"/technologies/dpyd-genotyping/"},{"id":"germline-testing","kind":"technology","name":"Germline (hereditary) testing","route":"/technologies/germline-testing/"},{"id":"oncology-pharmacogenomics","kind":"technology","name":"Pharmacogenomic testing before chemotherapy","route":"/technologies/oncology-pharmacogenomics/"},{"id":"topoisomerase-inhibitors","kind":"technology","name":"Topoisomerase-I inhibitors (and ADC payloads)","route":"/technologies/topoisomerase-inhibitors/"}],"bottleneck":[{"id":"b-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/"},{"id":"b-dose-optimisation","kind":"bottleneck","name":"Wrong doses","route":"/bottlenecks/b-dose-optimisation/"}],"paper":[{"id":"paper-henricks-lancet-oncol","kind":"paper","name":"DPYD genotype-guided dose individualisation of fluoropyrimidine therapy in patients with cancer: a prospective safety analysis","route":"/key-papers/paper-henricks-lancet-oncol/"}],"roadmap":[{"id":"chemotherapy-roadmap","kind":"roadmap","name":"Chemotherapy roadmap: mustard gas → curative combinations → the warhead inside smarter drugs","route":"/roadmaps/chemotherapy-roadmap/"}]}}