OnCo
ideasIdea

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

A cheap gene test before starting common chemotherapy identifies people at high risk of severe or fatal side effects so their dose can be lowered. Europe recommends it; many places still do not do it.

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.

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.
What would test it
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
Who has to act
payer
Cost to try
Small (under $1M)
Years to first evidence
2
Bottlenecks it attacks

Connected

8top

Pages like this

not linked directly; found by shared links

cancers

3
Colorectal cancerGastric & gastro-oesophageal junction cancerPancreatic ductal adenocarcinoma

technologies

3
Cytotoxic chemotherapyGermline (hereditary) testingTopoisomerase-I inhibitors (and ADC payloads)

bottlenecks

2
Toxicity and quality of life are undervaluedWrong doses