Lack of association between excretion of sorafenib in sweat and hand-foot skin reaction.
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.
Jain
Lokesh
L
Clinical Pharmacology Program, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
Gardner
Erin R
ER
Figg
William D
WD
Chernick
Milica S
MS
Kong
Heidi H
HH
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
D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D010862:Pilocarpine; D009536:Niacinamide; D000077157:Sorafenib