Androgen Mediation—and Antiandrogens Mitigation—of the Epidermal Growth Factor Receptor (EGFR) Inhibitor–Induced Rash: Results From a Pilot Randomized Trial and Small Translational Case Series

Background: Although 50% to 90% of patients who receive epidermal growth factor receptor (EGFR) inhibitors develop a rash, options for rash prevention or palliation remain limited. This issue is particularly important from a palliative care standpoint because these agents are prescribed only to patients with incurable cancer. Here, we report (1) gene expression profiling of skin biopsies from patients with an EGFR inhibitor–induced rash and (2) a randomized, placebo-controlled feasibility trial with the antiandrogen, spironolactone. Both investigations were undertaken to begin to explore the hypothesis that androgens mediate EGFR inhibitor–induced rash and that antiandrogens palliate it. Methods/Results: First, 4 skin biopsies from patients with EGFR inhibitor–induced rash (3 men and 1 woman) were subject to gene expression microarray profiling. A public data set of normal skin gene expression (Gene Expression Omnibus, GSE22998) served as a reference. Sixty percent of commonly interrogated androgen receptor genes (207 of 308 between the 2 data sets) were differentially expressed (P <.05) in the rash samples. Second, in a 17-patient double-blinded, placebo-controlled trial with topical spironolactone applied to the face, although the primary feasibility end point was not achieved, patients in the spironolactone arm received more doses of EGFR inhibitor, and anecdotal photographic evidence suggested salutatory effects of spironolactone on rash. Conclusions: Epidermal growth factor receptor inhibitor–induced rash appears to be androgen-mediated; antiandrogen therapy merits further study for rash prevention/palliation.