Methylenetetrahydrofolate Reductase (MTHFR) Variants and Severe Capecitabine Toxicity: A Case Report and Review of Literature.

Capecitabine is an oral prodrug metabolized into 5-fluorouracil (5-FU) and serves as a representative anticancer agent. While fluoropyrimidine treatment is usually well-tolerated, a subset of patients unfortunately experiences severe and sometimes life-threatening toxicity related to these compounds. This adverse reaction is frequently attributed to partial or complete deficiencies in the dihydropyrimidine dehydrogenase (DPD) enzyme. However, some patients may still suffer from severe toxic effects despite normal DPD screening results when treated with capecitabine. This paper presents the case of a Chinese woman with stage IIIB moderately differentiated adenocarcinoma of the lower rectum (cT3N2aM0) who exhibited severe toxicity after two weeks of neoadjuvant concurrent chemoradiotherapy in TNT mode at a low dose (825mg/m2 bid) of capecitabine. We found that this severe toxicity might be attributable to insufficient methylenetetrahydrofolate reductase (MTHFR) activity. To our knowledge, such reports are scarce in the medical literature concerning the Chinese population.