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

Jennifer Le-Rademacher, Kendrith Rowland, Pamela J. Atherton, Christopher Dakhil, Zhifu Sun, Angelina Tan, Lucy Schmidt, Phuong L Nguyen, Carmen Radecki Breitkopf, Mark Pittelkow, Donald Tindall, Smitha Menon, Aminah Jatoi

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
JournalAmerican Journal of Hospice and Palliative Medicine
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Androgen Antagonists
Exanthema
Epidermal Growth Factor Receptor
Androgens
Spironolactone
Gene Expression Profiling
Skin
Placebos
Biopsy
Gene Expression
Androgen Receptors
Palliative Care
Arm

Keywords

  • EGFR inhibitors
  • palliative care
  • quality of life
  • rash
  • skin
  • toxicity

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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. / Le-Rademacher, Jennifer; Rowland, Kendrith; Atherton, Pamela J.; Dakhil, Christopher; Sun, Zhifu; Tan, Angelina; Schmidt, Lucy; Nguyen, Phuong L; Radecki Breitkopf, Carmen; Pittelkow, Mark; Tindall, Donald; Menon, Smitha; Jatoi, Aminah.

In: American Journal of Hospice and Palliative Medicine, 01.01.2018.

Research output: Contribution to journalArticle

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abstract = "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.",
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AU - Atherton, Pamela J.

AU - Dakhil, Christopher

AU - Sun, Zhifu

AU - Tan, Angelina

AU - Schmidt, Lucy

AU - Nguyen, Phuong L

AU - Radecki Breitkopf, Carmen

AU - Pittelkow, Mark

AU - Tindall, Donald

AU - Menon, Smitha

AU - Jatoi, Aminah

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