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Study protocol for efficacy and safety of steroid-containing mouthwash to prevent chemotherapy-induced stomatitis in women with breast cancer: a multicentre, open-label, randomised phase 2 study
  1. Sayaka Kuba1,
  2. Kosho Yamanouchi2,
  3. Megumi Matsumoto3,
  4. Shigeto Maeda2,
  5. Toshiko Hatachi4,
  6. Soutome Sakiko5,
  7. Yumiko Kawashita5,
  8. Michi Morita1,
  9. Chika Sakimura6,
  10. Eiko Inamasu7,
  11. Kenichiro Shibata4,
  12. Ryota Otsubo3,
  13. Hiroshi Yano3,
  14. Seiichi Nose8,
  15. Junya Miyamoto9,
  16. Shuntaro Sato9,
  17. Kengo Kanetaka1,
  18. Hideki Taniguchi4,
  19. Masahiro Umeda10,
  20. Takeshi Nagayasu3,
  21. Susumu Eguchi1
  1. 1 Surgery, Nagasaki University School of Medicine Graduate School of Biomedical Sciences, Nagasaki, Japan
  2. 2 Surgery, National Hospital Organisation Nagasaki Medical Center, Omura, Nagasaki, Japan
  3. 3 Surgical Oncology, Nagasaki University School of Medicine Graduate School of Biomedical Sciences, Nagasaki, Japan
  4. 4 Surgery, Japanese Red Cross Nagasaki Atomic Bomb Hospital, Nagasaki, Japan
  5. 5 Oral Management Center, Nagasaki University Hospital, Nagasaki, Japan
  6. 6 Surgery, Nagasaki Harbor Medical Center City Hospital, Nagasaki, Japan
  7. 7 Hakujujikai Sasebo Chuo Hospital, Sasebo, Nagasaki, Japan
  8. 8 Pharmacy, Nagasaki University Hospital, Nagasaki, Japan
  9. 9 Clinical Research Center, Nagasaki University Hospital, Nagasaki, Japan
  10. 10 Clinical Oral Oncology, Nagasaki University School of Medicine Graduate School of Biomedical Sciences, Nagasaki, Japan
  1. Correspondence to Dr Sayaka Kuba; skuba{at}


Introduction Stomatitis is a frequent adverse event in patients undergoing chemotherapy for breast cancer. Stomatitis can hamper oral nutrition resulting in malnutrition, reduce quality of life and introduce the need for dose reductions and interruption of chemotherapy; however, there is currently no standard approach for preventing chemotherapy-induced stomatitis. We aimed to assess the safety and efficacy of a dexamethasone-based elixir mouthwash for preventing chemotherapy-induced stomatitis in patients with early breast cancer.

Methods and analysis In this multicenter, randomised, controlled phase 2 trial, we will randomly assign 120 women with early breast cancer undergoing chemotherapy to use of a dexamethasone-based elixir or standard oral care, to compare their preventive effects on chemotherapy-induced stomatitis. Patients will be assigned in a 1:1 ratio. Patients in the intervention group will receive chemotherapy, oral care and a dexamethasone-based elixir (10 mL 0.1 mg/mL; swish for 2 min and spit, four times daily for 9 weeks), and patients in the control group will receive chemotherapy and oral care. The primary endpoint is the difference in incidence of stomatitis between the two groups. The sample size allows for the detection of a minimum difference of 20% in the incidence of stomatitis between the two groups. Secondary endpoints are severity of stomatitis, duration of stomatitis, completion rate of chemotherapy and adverse events.

Ethics and dissemination All participants signed a written consent form, and the study protocol has been reviewed and approved by the Clinical Research Review Board of Nagasaki University (CRB7180001).

Trial registration number UMIN Clinical Trials Registry (UMIN000030489).

  • chemotherapy-induced stomatitis
  • dexamethasone-based elixir
  • randomised controlled phase 2 trial

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  • Contributors SK, KY, MM, SM and TH are responsible for conceiving and designing the trial, planning data analysis and collecting data, and are incharge of patient recruitment and treatment. MM, CS, EI, KS, RO and HY will participate in data collection and are incharge of patient recruitment and treatment. SN is responsible for preparing the dexamethasone-based elixir mouthwash. SS and YK are responsible for dental checkups and judging stomatitis and oral adverse events. JM and SS are responsible for the sample size and allocation. KK, HT, MU, TN and SE are responsible for planning the data analysis and analysing the data resulting from the trial. SK is responsible for screening the patients and data monitoring with attending the physician. SK, JM and SS will access the final trial dataset and analyse the data. All authors have contributed to and approved the final version of this manuscript for publication.

  • Funding Funding for this research was obtained through Project Mirai Cancer Research Grants and grants from the Nagasaki-ken Medical Association.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval This study was approved by the Clinical Research Review Board of Nagasaki University, Japan. Any changes that need to be made to the trial protocol will be communicated to all investigators and ethics committees, and to the trial registry. The protocol (version 1) has been designed and will be conducted in accordance with the Declaration of Helsinki (1964) and the Clinical Trial Act (2018).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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