Efficacy and safety of rebamipide liquid for chemoradiotherapy-induced oral mucositis in patients with head and neck cancer: a multicenter, randomized, double-blind, placebo-controlled, parallel-group phase II study

BMC Cancer

Research Article

S. Iwae¹  M. Tahara²  Y. Hasegawa³  K. Matsuura⁴  N. Monden⁵  H. Nishimori⁶  K. Tanaka⁷  S. Takahashi⁸  K. Okami⁹  M. Fujii^1,10  T. Fujii^1,11  S. Hirano^1,12  I. Ota^1,13  T. Ogawa^1,14  H. Kojima^1,15  Y. Fujimoto^1,16  T. Ueda^1,17  T. Yokota^1,18  T. Beppu^1,19  K. Sasaki^2,20  Y. Naka^2,21  Y. Matsushima^2,21  S. Ueda^2,22 

[1] Department of Head and Neck Cancer, Hyogo Cancer Center, 673-8558, Akashi, Japan;Department of Head and Neck Medical Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, 277-8577, Chiba, Japan;Department of Head and Neck Surgery, Aichi Cancer Center Hospital and Research Institute, 1-1 Kanokoden, Chikusa-ku, 464-8681, Nagoya, Japan;Department of Head and Neck Surgery, Miyagi Cancer Center, 47-1 Medeshimashiote, 981-1293, Natori, Japan;Department of Head and Neck Surgery, Shikoku Cancer Center, 791-0280, Matsuyama, Japan;Department of Hematology and Oncology, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama, Japan;Department of Medical Oncology, Kindai University Faculty of Medicine, Sayama, 589-0014, Osaka, Japan;Department of Medical Oncology, The Cancer Institute Hospital of JFCR, 3-8-31 Ariake, Koto-ku, 135-8550, Tokyo, Japan;Department of Otolaryngology, Center of Head and Neck Surgery, Tokai University, 143 Shimokasuya, Isehara, Japan;Department of Otolaryngology, Eiju General Hospital, 2-23-16 Higashiueno, Taito-ku, 110-8645, Tokyo, Japan;Department of Otolaryngology, Head and Neck Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, 537-8511, Osaka, Japan;Department of Otolaryngology-Head and Neck Surgery, Kyoto University Hospital, 54 Kawaharacho, Shogoin, Sakyo-ku, 606-8507, Kyoto, Japan;Department of Otolaryngology-Head and Neck Surgery, Nara Medical University, 634-8522, Kashiharashi, Japan;Department of Otolaryngology-Head and Neck Surgery, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan;Department of Otorhinolaryngology, Jikei University School of Medicine, 3-19 Nishi-Shinbashi, Minato-ku, 105-0003, Tokyo, Japan;Department of Otorhinolaryngology, Nagoya University, Graduate School of Medicine, 65 Tsurumai-cho, Shouwa-ku, 466-8550, Nagoya, Aichi, Japan;Department of Otorhinolaryngology-Head and Neck Surgery, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, 734-8551, Hiroshima, Japan;Division of Gastrointestinal Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, 411-8777, Shizuoka, Japan;Division of Head and Neck Surgery, Saitama Cancer Center, 780 Komuro, Inamachi, Kitaadachi-gun, Saitama, Japan;Head and Neck, Chiba Cancer Center, 666-2 Nitona-cho, Chuo-ku, 260-0801, Chiba, Japan;Headquarters of New Product Evaluation and Development, Otsuka Pharmaceutical Co., Ltd., Shinagawa Grand Central Tower, 2-16-4 Konan, Minato-ku, 108-8242, Tokyo, Japan;Medical Oncology, Nara Hospital, Kindai University School of Medicine, 1248−1 Otoda-cho, Ikoma, 630-0293, Nara, Japan;

关键词: Chemoradiotherapy;    Head and neck cancer;    Oral mucositis;    Rebamipide liquid;    Randomized;    Placebo-controlled;   

DOI  :  10.1186/s12885-017-3295-4

 received in 2016-12-10, accepted in 2017-04-24,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundRecent preclinical and phase I studies have reported that rebamipide decreased the severity of chemoradiotherapy-induced oral mucositis in patients with oral cancer. This placebo-controlled randomized phase II study assessed the clinical benefit of rebamipide in reducing the incidence of severe chemoradiotherapy-induced oral mucositis in patients with head and neck cancer (HNC).MethodsPatients aged 20–75 years with HNC who were scheduled to receive chemoradiotherapy were enrolled. Patients were randomized to receive rebamipide 2% liquid, rebamipide 4% liquid, or placebo. The primary endpoint was the incidence of grade ≥ 3 oral mucositis determined by clinical examination and assessed by central review according to the Common Terminology Criteria of Adverse Events version 3.0. Secondary endpoints were the time to onset of grade ≥ 3 oral mucositis and the incidence of functional impairment (grade ≥ 3) based on the evaluation by the Oral Mucositis Evaluation Committee.ResultsFrom April 2014 to August 2015, 97 patients with HNC were enrolled, of whom 94 received treatment. The incidence of grade ≥ 3 oral mucositis was 29% and 25% in the rebamipide 2% and 4% groups, respectively, compared with 39% in the placebo group. The proportion of patients who did not develop grade ≥ 3 oral mucositis by day 50 of treatment was 57.9% in the placebo group, whereas the proportion was 68.0% in the rebamipide 2% group and 71.3% in the rebamipide 4% group. The incidences of adverse events potentially related to the study drug were 16%, 26%, and 13% in the placebo, rebamipide 2%, and rebamipide 4% groups, respectively. There was no significant difference in treatment compliance among the groups.ConclusionsThe present phase II study suggests that mouth washing with rebamipide may be effective and safe for patients with HNC receiving chemoradiotherapy, and 4% liquid is the optimal dose of rebamipide.Trial registrationClinicalTrials.gov under the identifier NCT02085460 (the date of trial registration: March 11, 2014).

【 授权许可】

CC BY   
© The Author(s). 2017