Placebo-controlled phase II study of vitamin K3 cream for the treatment of cetuximab-induced rash

Abstract

Purpose

Cetuximab inhibits the epidermal growth factor receptor (EGFR), and papulopustular eruptions is a frequent side effect. Vitamin K3 (menadione) has preclinically shown to be a potential activator of the EGFR by phosphorylating the receptor (pEGFR). The present randomised study investigated the effect of a vitamin K3 cream on cetuximab-induced rash.

Materials and methods

Thirty patients were included in this double-blinded placebo-controlled trial. Patients receiving cetuximab 500 mg/m2 every second week plus chemotherapy for metastatic cancer were included. In each patient, vitamin K3 cream and placebo were applied twice daily on two separate areas of the skin of minimum 10 × 10 cm for up to 2 months. Papulopustular eruptions were evaluated clinically and monitored by clinical photos. Skin biopsies, from ten patients taken before and after 1 month of treatment from each treatment area, were stained for EGFR and pEGFR.

Results

Application of vitamin K3 cream twice daily during treatment with cetuximab did not reduce the number of papulopustular eruptions, and this was independent of the use of systemic tetracycline. No significant changes in the staining of EGFR or pEGFR were observed in the skin of the vitamin K3-treated area compared to the placebo area.

Conclusion

The present data do not support any clinical or immunohistochemical benefit of using vitamin K3 cream for cetuximab-induced rash.

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Acknowledgements

We acknowledge the skilled work of Mrs. Inger Marie Horsman, Inger Marie Thuesen and Dorthe Grand, conducting the animal experiments at Dept. of Experimental Clinical Oncology, Aarhus, Denmark.

The study was supported by a grant from “A.P. Møller og Hustru Chastine Mc-Kinney Møllers Fond til almene Formaal; Fondet til Lægevidenskabens Fremme” and Merck KGaA, Darmstadt, Germany. The study was designed, conducted and the data analysed independently of the company. The authors are fully responsible for the content of this manuscript, and the views and opinions described in the publication reflect solely those of the authors.

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Correspondence to Jesper Grau Eriksen.

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Conflicts of interest

The study was supported by a grant from a public foundation “A.P. Møller og Hustru Chastine Mc-Kinney Møllers Fond til almene Formaal; Fondet til Lægevidenskabens Fremme” and the commercial company Merck KGaA, Darmstadt, Germany. The study was designed, conducted and the data analysed independently of the company. The authors are fully responsible for the content of this manuscript, and the views and opinions described in the publication reflect solely those of the authors. None of the authors have any conflicts of interest to report related to the present study. The authors allow the journal to review the data if requested.

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Eriksen, J.G., Kaalund, I., Clemmensen, O. et al. Placebo-controlled phase II study of vitamin K3 cream for the treatment of cetuximab-induced rash. Support Care Cancer 25, 2179–2185 (2017). https://doi.org/10.1007/s00520-017-3623-x

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Keywords

  • Skin toxicity
  • Rash
  • EGFR-inhibitor
  • Cetuximab
  • Phase II