Why are European patients better able to tolerate high doses of capecitabine than US patients?

This is a really interesting question. One theory relates to folic acid content in food. Capecitabine (Xeloda) is an oral prodrug of fluorouracil (5-FU). 5-FU is frequently given with leucovorin, which is a reduced form of folic acid. This increases the efficacy — and toxicity — of 5-FU.

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In the United States, many foods are enriched with folic acid. This exposure to more folic acid may explain why patients in the United States experience more adverse effects from capecitabine than their counterparts elsewhere.