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Severe Capecitabine Toxicity Associated With a Rare DPYD Variant Identified Through Whole-Genome Sequencing.

Fluoropyrimidine drugs, both fluorouracil (FU) and its prodrug capecitabine, are widely used in the treatment of solid tumors such as breast, colorectal, and gastric cancers. Over 2 million patients newly diagnosed with cancer are treated each year with fluoropyrimidines. Between 10% and 40% of these patients develop severe, sometimes life-threatening toxicities, which may include mucositis, neutropenia, nausea, severe diarrhea, vomiting, stomatitis, and hand-foot syndrome. These toxicities can be caused by genetic variants in DPYD, the gene that encodes for dihydropyrimidine dehydrogenase (DPD), the rate-limiting enzyme responsible for FU catabolism.