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Aim To independently assess the impact of mandatory testing using an extended DPYD variant panel (ToxNav®) and consequent dose adjustment of Capecitabine/5-FU on recorded quantitative toxicity, symptoms of depression, and hospital costs. Methods We used propensity score matching (PSM) to match 466 patients tested with ToxNav® with 1556 patients from a historical cohort, and performed regression analysis to estimate the impact of ToxNav®on toxicity, depression, and hospital costs. Results ToxNav® appeared to reduce the likelihood of experiencing moderate (OR: 0.59; 95%CI: 0.45–0.77) and severe anaemia (OR: 0.55; 95%CI: 0.33–0.90), and experience of pain for more than 4 days a week (OR: 0.50; 95%CI: 0.30–0.83), while it increased the likelihood of mild neutropenia (OR: 1.73; 95%CI: 1.27–2.35). It also reduced the cost of chemotherapy by 12% (95%CI: 3–31) or £9765, the cost of non-elective hospitalisation by 23% (95%CI: 8–36) or £2331, and the cost of critical care by 21% (95%CI: 2–36) or £1219 per patient. For the  DPYD  variant associated with critical risk of toxicity (rs3918290), the improved non-elective hospital costs were &gt; £20,000, whereas variants associated with hand-foot syndrome toxicity had no detectable cost improvement. Conclusion Upfront testing of DPYD variants appears to reduce the toxicity burden of Capecitabine and 5-FU in cancer patients and can lead to substantial hospital cost savings, only if the dose management of the drugs in response to variants detected is standardised and regulated.

bmc cancer

Can upfront DPYD extended variant testing reduce toxicity and associated hospital costs of fluoropyrimidine chemotherapy? A propensity score matched analysis of 2022 UK patients