Severe toxicity of capecitabine in a patient with DPD deficiency after a safe FEC-100 experience: why we should test DPD deficiency in all patients before high-dose fluoropyrimidines.

We report the case of a 44-year-old patient who experienced severe toxicity while being treated with capecitabine at standard dose for metastatic breast cancer. As the patient had already received 5-FU within the FEC protocol (5-FU 500 mg/m, epirubicin 100 mg/m, and cyclophosphamide 500 mg/m) 10 years ago without experiencing any severe adverse event, no DPD deficiency testing was performed before capecitabine treatment. Nevertheless, she experienced severe diarrhea and grade 2 hand-foot syndrome from the first cycle, forcing her to stop the treatment. Phenotypic and genotypic investigation of DPD activity revealed that the patient had a partial deficiency and had therefore been exposed to a higher risk of developing severe toxicities on fluoropyrimidines. This case proves that tolerance to low-dose fluoropyrimidines does not preclude DPD deficiency and the occurrence of severe toxicities if higher doses of fluoropyrimidines are used as a second-line treatment. It emphasizes the role of DPD phenotyping testing based on uracilemia in patients scheduled for fluoropyrimidine drugs, even if previous courses with low-dose 5-FU were safely administered.