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DPD Deficiency — SCE Medical Oncology MCQ

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HardOncological EmergenciesDPD DeficiencySCE Medical Oncology

A 58-year-old woman receiving capecitabine + oxaliplatin for colorectal cancer presents to A&E with severe stomatitis, bloody diarrhoea (15 episodes/day), and neutrophils 0.2 × 10⁹/L. Pre-treatment DPYD genotyping was NOT performed. This presentation is consistent with what pharmacogenomic condition?

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Correct answer: C — Severe early fluoropyrimidine toxicity caused by reduced DPD activity

Profound early mucosal and marrow toxicity during capecitabine exposure is the characteristic signal of reduced DPD activity. Reduced UGT1A1 activity producing severe early irinotecan toxicity: UGT1A1 governs irinotecan metabolism rather than capecitabine catabolism. Reduced TPMT activity producing severe early thiopurine toxicity: TPMT is relevant to thiopurines rather than fluoropyrimidines. Reduced CYP2C8 activity producing severe early paclitaxel toxicity: CYP2C8 affects paclitaxel and does not explain this fluoropyrimidine syndrome. Reduced carbonyl-reductase activity producing severe early anthracycline toxicity: carbonyl reduction is relevant to anthracyclines, not capecitabine.

Reference: 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