title: Lack of association between excretion of sorafenib in sweat and hand-foot skin reaction.
abstract: OBJECTIVE
  To determine if excretion of sorafenib in sweat is associated with hand-foot skin reaction in patients receiving sorafenib.
  
  
  METHODS
  Prospective pilot study.
  
  
  METHODS
  Outpatient clinic of a cancer research institution.
  
  
  METHODS
  Two patients who were receiving sorafenib and developed a hand-foot skin reaction of at least grade 1 and two healthy subjects (controls).
  
  
  METHODS
  Sweat production was stimulated in both the patients with hand-foot skin reaction and the healthy subjects by means of pilocarpine iontophoresis.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Clinical Pharmacology Program, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Lokesh
authors.initials: L
authors.lastname: Jain
authors.forename: Erin R
authors.initials: ER
authors.lastname: Gardner
authors.forename: William D
authors.initials: WD
authors.lastname: Figg
authors.forename: Milica S
authors.initials: MS
authors.lastname: Chernick
authors.forename: Heidi H
authors.initials: HH
authors.lastname: Kong
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000032:analysis / Q000097:blood / Q000378:metabolism; D001557:Benzenesulfonates / Q000009:adverse effects* / Q000032:analysis* / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D003875:Drug Eruptions / Q000209:etiology*; D005260:Female; D005533:Foot Dermatoses / Q000139:chemically induced*; D006229:Hand Dermatoses / Q000139:chemically induced*; D006801:Humans; D007478:Iontophoresis; D057230:Limit of Detection; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D010862:Pilocarpine / Q000494:pharmacology; D010865:Pilot Projects; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000032:analysis / Q000097:blood / Q000378:metabolism; D011725:Pyridines / Q000009:adverse effects* / Q000032:analysis* / Q000097:blood; D012720:Severity of Illness Index; D000077157:Sorafenib; D013542:Sweat / Q000737:chemistry*; D053719:Tandem Mass Spectrometry
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D010862:Pilocarpine; D009536:Niacinamide; D000077157:Sorafenib