DPYD c.2846A>T — SCE Medical Oncology MCQ

Correct answer: E — Start fluoropyrimidine at about half dose, then titrate using toxicity and response

A single c.2846A>T reduced-function DPYD allele supports an approximately fifty-percent starting dose followed by careful titration. Start fluoropyrimidine at three-quarter dose, then titrate using toxicity and response: the recommended initial reduction for this decreased-function heterozygote is approximately fifty percent. Start fluoropyrimidine at one-quarter dose, then titrate using toxicity and response: one-quarter dosing is generally more conservative than required for this genotype. Start full-dose fluoropyrimidine with intensified toxicity and response monitoring: monitoring cannot offset predictable excess exposure from reduced DPD activity. Use uracil-tegafur at full dose, then titrate using toxicity and response: tegafur is also converted to fluorouracil and remains DPD dependent.

Reference: CPIC guideline for fluoropyrimidines and DPYD genotype (Published January 2018; current variant-specific dosing framework): https://pmc.ncbi.nlm.nih.gov/articles/PMC5760397/; MHRA fluoropyrimidines: test all patients for DPD deficiency before treatment (Published October 2020; current MHRA safety advice): https://www.gov.uk/drug-safety-update/5-fluorouracil-intravenous-capecitabine-and-tegafur-containing-products-test-all-patients-for-dpd-deficiency-before-initiation-to-identify-those-at-increased-risk-of-severe-and-fatal-toxicity