# Test DPYD, UGT1A1 and TPMT/NUDT15 before the first dose, everywhere

Source: https://onco.cc/ideas/idea-tr1-pre-emptive-pharmacogenomic-testing/  
OnCo record `idea-tr1-pre-emptive-pharmacogenomic-testing` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- 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.
- Proposed 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

## Sources

- CPIC guideline: fluoropyrimidines and DPYD: https://cpicpgx.org/guidelines/guideline-for-fluoropyrimidines-and-dpyd/
- EMA: fluorouracil and related substances (DPD testing): https://www.ema.europa.eu/en/medicines/human/referrals/fluorouracil-fluorouracil-related-substances-capecitabine-tegafur-flucytosine-containing-medicinal-products

## Connected records

- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Gastric & gastro-oesophageal junction cancer](https://onco.cc/cancers/gastric/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- technologies: [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [Germline (hereditary) testing](https://onco.cc/technologies/germline-testing/), [Topoisomerase-I inhibitors (and ADC payloads)](https://onco.cc/technologies/topoisomerase-inhibitors/)
- bottlenecks: [Toxicity and quality of life are undervalued](https://onco.cc/bottlenecks/b-toxicity-qol/), [Wrong doses](https://onco.cc/bottlenecks/b-dose-optimisation/)
- roadmaps: [Chemotherapy roadmap: mustard gas → curative combinations → the warhead inside smarter drugs](https://onco.cc/roadmaps/chemotherapy-roadmap/)

---
JSON: https://onco.cc/api/v1/entities/idea-tr1-pre-emptive-pharmacogenomic-testing.json