Clinical response to capecitabine in a DPYD*2A 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.