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Topical doxycycline foam 4% for prophylactic management of epidermal growth factor receptor inhibitor skin toxicity: an exploratory phase 2, randomized, double-blind clinical study

  • Einat Shacham Shmueli
  • Ravit Geva
  • Nirit Yarom
  • Ayala Hubert
  • Rita Keynan
  • Tal H. Kedem
  • Meir Eini
  • Dov Tamarkin
  • Mitchell ShirvanEmail author
Original Article
  • 49 Downloads

Abstract

Purpose

Acneiform rash, a common toxicity of epidermal growth factor receptor inhibitors (EGFRIs), can cause patient discomfort, warranting changes in treatment. This study investigated the safety, tolerability, and efficacy of a novel doxycycline foam, FDX104 4%, for managing EGFRI-related skin toxicity.

Methods

This was an exploratory phase 2, randomized, double-blind, placebo-controlled study. Subjects had metastatic colorectal cancer and were being treated with either cetuximab or panitumumab plus chemotherapy. Treatment (twice-daily topical FDX104 4% on one side of the face and vehicle foam on the other for 5 weeks) was initiated 7 ± 3 days prior to EGFRI therapy. Rash severity, safety, and tolerability were evaluated at 2 and 4 weeks after EGFRI start.

Results

The mean maximal rash grade was lower with FDX104 4% vs vehicle, and fewer subjects developed moderate-to-severe (grades 2–3) rash. On the Global Severity Score scale, a statistically significant difference favored FDX104 4% over vehicle (P = .047). Adverse events (AEs) (n = 68) occurred in 20 subjects; most were mild or moderate. The most common AEs were oral mucositis, nausea, and vomiting, common to chemotherapy and EGFRI treatment. Study-drug–related AEs were experienced by five subjects and consisted of mild, local skin reactions. No study-drug–related systemic side effects were reported.

Conclusion

Twice-daily, topical administration of FDX104 4% as an adjunct to either cetuximab or panitumumab was safe and well tolerated, and appeared to prevent the onset of rash, especially severe rash.

ClinicalTrials.gov identifier

Trial Registration NCT02239731

Keywords

Epidermal growth factor inhibitor Acneiform rash Skin toxicity Colorectal cancer Topical doxycycline foam FDX104 

Notes

Acknowledgments

The authors wish to thank Dr. Dror Rom, Prosoft Clinical, Wayne, PA, USA for the statistical analysis.

Funding information

This study was funded by Foamix Pharmaceuticals, Inc. Editorial support was provided by Giang Nguyen, PhD, of P value communications.

Compliance with ethical standards

Conflict of interest

This study was supported by Foamix Pharmaceuticals. Einat Shacham Shmueli served as principal investigator on this study and has received a grant from Foamix Pharmaceuticals. Ravit Geva, Nirit Yarom, and Ayala Hubert served as investigators on this study. Rita Keynan, Tal Hetzroni Kedem, Dov Tarmakin, and Mitchell Shirvan are employees of Foamix Pharmaceuticals. Meir Eini serves as a consultant for Foamix Pharmaceuticals. Mitchell Shirvan, Tal Hetzroni, and Meir Eini receive stock options from Foamix Pharmaceuticals. Ravit Geva reports other from MSD, Novartis, BMS, Roche, Janssen, Takeda, Medison, Merck, and Pfizer, outside the submitted work. The authors state that they have full control of all primary data, and they agree to allow the journal to review their data if requested.

Supplementary material

520_2018_4600_MOESM1_ESM.docx (1.5 mb)
ESM 1 (DOCX 1574 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Einat Shacham Shmueli
    • 1
  • Ravit Geva
    • 2
  • Nirit Yarom
    • 3
  • Ayala Hubert
    • 4
  • Rita Keynan
    • 5
  • Tal H. Kedem
    • 5
  • Meir Eini
    • 5
  • Dov Tamarkin
    • 5
  • Mitchell Shirvan
    • 5
    Email author
  1. 1.Sheba Medical CenterTel-HashomerIsrael
  2. 2.Tel Aviv Sourasky Medical CenterTel AvivIsrael
  3. 3.Assaf Harofeh Medical CenterTzrifinIsrael
  4. 4.Hadassah Medical CenterJerusalemIsrael
  5. 5.Foamix Pharmaceuticals Ltd.RehovotIsrael

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