Clinical response to capecitabine in a <i>DPYD*2A</i> homozygous patient: Case report and therapeutic guidance

Complete dihydropyrimidine dehydrogenase (DPD) deficiency due to homozygous DPYD*2A is a contraindication for fluoropyrimidines because of the extreme risk of life-threatening toxicity. We report a 36-year-old male with metastatic rectal adenocarcinoma and complete DPD deficiency who received ultra-low-dose capecitabine in combination with oxaliplatin and cetuximab. Initial dosing of capecitabine 150 mg on Days 1, 6 and 16 of a 21-day cycle (0.76% of the BSA-based standard regimen) caused Grade 3 mucositis, but further dose reduction to capecitabine 150 mg on Days 1 and 8 of a 21-day cycle (0.50%) improved tolerability. Pharmacokinetic analyses revealed markedly prolonged 5-fluorouracil exposure with undetectable fluoro-β-alanine (FBAL), consistent with complete DPD deficiency. Despite the minimal dosing, a near-complete metabolic response was achieved after four cycles, enabling surgical resection of residual disease. This case illustrates that carefully individualized ultra-low-dose capecitabine, guided by pharmacokinetics and toxicity monitoring, can provide meaningful clinical benefit in patients with complete DPD deficiency. These findings highlight the therapeutic potential of a precision dosing approach in this rare but clinically challenging setting.