Analysis of intercellular lipids in the stratum corneum of patients with capecitabine-induced hand-foot syndrome: comparison with the stratum corneum of healthy individuals.

PURPOSE: Capecitabine (CAP) side effect, a prodrug of 5-fluorouracil (5-FU), is hand-foot syndrome (HFS), a localized skin disorder of the hands and feet that is believed to induce a decrease in skin barrier function. Stratum corneum (SC) lipids play an important role in skin barrier function; therefore, this study compared the SC lipid structure and composition of healthy participants with those of patients with CAP-induced HFS.

METHODS

Forty patients receiving a combination regimen of CAP and oxaliplatin as adjuvant chemotherapy for colorectal cancer were enrolled. All patients received 1,000 mg/m2 twice daily on days 1-14. SC samples were obtained from 11 patients with CAP-induced HFS (CSC). The SC lipid structure was analyzed using synchrotron X-ray diffraction. SC lipid components, ceramides (CERs), free fatty acids (FFAs), CAP, and its metabolites in CSC samples were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).

RESULTS

In healthy SC (HSC), lipids formed two lamellar phases. Hexagonal and orthorhombic hydrocarbon chain packing was observed in lateral lipid organization. However, in CSC, these structures have almost disappeared. UPLC-MS/MS analysis revealed that the composition of CER and FFA differed between CSC and HSC, and that the carbon chain length of SC lipid components in CSCs was reduced compared to that in HSCs. 5-FU was detected in CSCs at 3.4 ± 1.4 ng/mg.

CONCLUSION

CAP induces changes in SC lipid structure due to changes in SC lipid composition and a decrease in carbon chain length in CSCs. CAP-induced HFS is associated with 5-FU accumulation in SC.