Atypical hand-and-foot syndrome in an African American patient treated with capecitabine with normal DPD activity: is there an ethnic disparity?

Fluoropyrimidines constitute the backbone of chemotherapy regimens for gastrointestinal tumors, especially colorectal cancer (CRC). Comparison of oral and intravenous fluoropyrimidine treatments in patients with CRC has shown that hand-and-foot syndrome (HFS) (all grades) has the most frequently reported association with toxicity from capecitabine, an oral fluoropyrimidine. Present grading guidelines are generalized to patients belonging to all ethnicities. However, we noticed varying pattern and degree of manifestations of all grades of HFS in non-white patients as compared with white patients. This article presents the case of a 69-year-old African American man with a gastric adenocarcinoma status post gastrectomy who received 5-fluorouracil (5-FU) plus leucovorin for 5 days, to be followed by radiation plus capecitabine given 5 days per week for 5 weeks, and then 8 weeks of capecitabine monotherapy. Capecitabine was substituted because of severe toxicity with 5-FU after determining that the level of dihydropyrimidine dehydrogenase (DPD), the rate-limiting enzyme in the metabolism of fluoropyrimidines, was within normal limits. He developed discoloration of his palms consistent with HFS, contrary to the pattern and degree of HFS reported in the current guidelines as proposed in the drug insert. This case suggests that the pattern of cutaneous manifestations related to fluoropyrimidines may vary in patients with different ethnic backgrounds, especially whites Versus non-whites. This finding becomes more important as our recent findings suggest that DPD deficiency may be more common among African Americans. This case also suggests that severe toxicity to infusional 5-FU might not be indicative of severe toxicity to oral fluoropyrimidine drugs.