Lack of association between excretion of sorafenib in sweat and hand-foot skin reaction

Study Objective. To determine if excretion of sorafenib in sweat is associated with hand-foot skin reaction in patients receiving sorafenib. Design. Prospective pilot study. Setting. Outpatient clinic of a cancer research institution. Patients. Two patients who were receiving sorafenib and developed a hand-foot skin reaction of at least grade 1and two healthy subjects (controls). Intervention. Sweat production was stimulated in both the patients with hand-foot skin reaction and the healthy subjects by means of pilocarpine iontophoresis. Measurements and Main Results. Sweat samples were collected from the patients with hand-foot skin reaction and from the healthy subjects. Using liquid chromatography - tandem mass spectrometry, sorafenib concentrations were measured in the sweat samples. Sweat samples from the healthy subjects were spiked with known concentrations of sorafenib to determine the lower limit of quantification of the assay, which was determined to be 5 ng/ml. Sorafenib concentrations in the samples from the patients with hand-foot skin reaction were undetectable based on the assay's sensitivity. Conclusion. Our results suggest that hand-foot skin reaction in patients receiving sorafenib is not associated with excretion of sorafenib in sweat. Further studies are needed to understand the mechanism of hand-foot skin reaction, a treatment-limiting adverse effect of multikinase inhibitors.