Suspected capecitabine-induced fatal toxicity in the context of a new DPYD variant

We present the case of a male in his early 70s who died after receiving adjuvant chemotherapy, probably due to an undiagnosed dihydropyrimidine dehydrogenase (DPYD) deficiency. Despite normal results from standard DPYD genotyping prior to treatment, he developed severe gastrointestinal toxicity that progressed to bowel ischaemia and ultimately death. This case underscores the potential limitations of current genotyping approaches, which may not detect rare or functionally significant DPYD variants. It also highlights the need for a cautious and comprehensive approach to fluoropyrimidine therapy, especially in patients who develop unexpected toxicity, while recognising that other contributing factors may be involved.