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A single-arm, phase 2 study of steroid-containing mouthwash for the prevention of everolimus-associated stomatitis in multiple tumor types

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Abstract

Background

Everolimus is a mammalian target of rapamycin inhibitor used in the treatment of multiple tumor types, and its most common toxicity, stomatitis, can affect patient quality of life. Recent studies in breast cancer have supported the efficacy of steroid mouthwash for the prevention of everolimus-associated stomatitis. However, a few studies have been reported to date, and none have examined this effect in other tumor types.

Methods

This single-arm phase 2 study was designed to evaluate the efficacy of steroid-containing mouthwash for the prevention of stomatitis in patients with multiple tumor types receiving everolimus. The primary outcome was incidence of grade ≥ 2 stomatitis at 8 weeks of everolimus with steroid-containing mouthwash prophylaxis. We also assessed the stability of steroid-containing mouthwash components.

Results

Twenty-nine patients were evaluated, of which 76% had breast cancer and 24% had neuroendocrine tumors originating in the lung, gastrointestinal tract, pancreas, or of unknown primary origin. Grade ≥ 2 stomatitis incidence at 8 weeks was 28.1% (90% CI 16.2–46.1); the higher confidence limit exceeded the prespecified threshold of 30%. No patients developed grade ≥ 3 stomatitis. Most stomatitis occurred behind the oral cavity, with no lesions observed on the lips or floor of the mouth.

Conclusions

Our findings did not support a prophylactic effect of steroid-containing mouthwash on everolimus-associated stomatitis. Given the needs of prevention of everolimus-associated stomatitis in various tumor types, further studies in a larger population using a randomized controlled trial design are, therefore, required to confirm the efficacy of steroid-containing mouthwash.

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Acknowledgements

We thank Edanz Group for English editing a draft of this manuscript.

Funding

No specific funding has been provided for this study.

Author information

Authors and Affiliations

  1. Department of Breast Oncology, Aichi Cancer Center, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan

    Masaya Hattori, Haruru Kotani, Masataka Sawaki, Akiyo Yoshimura, Naomi Gondo, Yayoi Adachi & Hiroji Iwata

  2. Department of Head and Neck Surgery, Aichi Cancer Center, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan

    Sumitaka Hagiwara

  3. Department of Pharmacy, Aichi Cancer Center, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan

    Michiko Tatematsu & Yasunari Mizuno

  4. Aichi Prefectural Institute of Public Health, 7-6 Tsujimachi aza nagare, Kita-ku, Nagoya, 462-8576, Japan

    Masahiko Tachi

  5. Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Susumu Hijioka

  6. Department of Thoracic Oncology, Aichi Cancer Center, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan

    Junichi Shimizu

  7. Department of Clinical Oncology, Aichi Cancer Center, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan

    Masashi Andoh

  8. Innovative Clinical Research Center, Kanazawa University, Kakuma-machi, Kanazawa, 920-1192, Japan

    Kenichi Yoshimura

Authors
  1. Masaya Hattori
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  2. Sumitaka Hagiwara
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Contributions

M.H.: conceptualization, data curation, formal analysis, investigation, resources and writing—original draft, and writing—review and editing. S.H.: formal analysis, data curation, investigation, methodology, and writing—review and editing. H.K.: project administration, investigation, resources, and methodology. M.T.: investigation, methodology, and resources. M.T.: data curation, formal analysis, methodology, investigation, writing—original draft, and writing—review and editing. S.H.: investigation, resources, supervision, and writing—review and editing. J.S.: investigation, resources, supervision, and writing—review and editing. M.A.: resources, supervision, and writing—review and editing. Y.M.: investigation, methodology, and resources. M.S.: investigation and resources. A.Y.: investigation and resources. N.G.: investigation and resources. Y.A.: investigation and resources. K.Y.: formal analysis, methodology, and supervision. H.I.: conceptualization, supervision, and writing—review and editing.

Corresponding author

Correspondence to Masaya Hattori.

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Conflict of interest

Masaya Hattori received honoraria from Chugai Pharmaceutical, Eli Lilly Japan, Novartis Pharma, AstraZeneca, Pfizer Japan, and Eisai for work performed outside of the current study. Susumu Hijioka received honoraria from Novel Pharma, Novartis Pharma, and Tenjin Pharma for work performed outside of the current study. Hiroji Iwata received research funding from Chugai Pharmaceutical, MSD K.K, Eli Lilly Japan, and Novartis Pharma for work performed outside of the current study; received honoraria from Chugai Pharmaceutical, Daiichi Sankyo, and AstraZeneca for work performed outside of the current study; and is a member of scientific advisory board of Daiichi Sankyo, Chugai Pharmaceutical, Eli Lilly Japan, Kyowa Hakko Kirin, Pfizer Japan, Novartis Pharma, and AstraZeneca for work performed outside of the current study. The other authors have no conflicts of interest to declare.

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Hattori, M., Hagiwara, S., Kotani, H. et al. A single-arm, phase 2 study of steroid-containing mouthwash for the prevention of everolimus-associated stomatitis in multiple tumor types. Int J Clin Oncol 24, 1320–1327 (2019). https://doi.org/10.1007/s10147-019-01476-0

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