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

• Published in: Pharmacotherapy Vol. 30; no. 1; p. 52
• Main Authors: Jain, Lokesh, Gardner, Erin R, Figg, William D, Chernick, Milica S, Kong, Heidi H
• Format: Journal Article
• Language: English
• Published: United States 01.01.2010
• Subjects: Antineoplastic Agents - adverse effects; Antineoplastic Agents - analysis; Antineoplastic Agents - blood; Antineoplastic Agents - metabolism; Benzenesulfonates - adverse effects; Benzenesulfonates - analysis; Benzenesulfonates - blood; Chromatography, High Pressure Liquid; Drug Eruptions - etiology; Female; Foot Dermatoses - chemically induced; Hand Dermatoses - chemically induced; Humans; Iontophoresis; Limit of Detection; Male; Middle Aged; Niacinamide - analogs & derivatives; Phenylurea Compounds; Pilocarpine - pharmacology; Pilot Projects; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - analysis; Protein Kinase Inhibitors - blood; Protein Kinase Inhibitors - metabolism; Pyridines - adverse effects; Pyridines - analysis; Pyridines - blood; Severity of Illness Index; Sorafenib; Sweat - chemistry; Tandem Mass Spectrometry
• ISSN: 1875-9114
• DOI: 10.1592/phco.30.1.52

To determine if excretion of sorafenib in sweat is associated with hand-foot skin reaction in patients receiving sorafenib. Prospective pilot study. Outpatient clinic of a cancer research institution. Two patients who were receiving sorafenib and developed a hand-foot skin reaction of at least grade 1 and two healthy subjects (controls). Sweat production was stimulated in both the patients with hand-foot skin reaction and the healthy subjects by means of pilocarpine iontophoresis. 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. 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.