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BMC Cancer. 2017 May 5;17(1):314. doi: 10.1186/s12885-017-3295-4.

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.

Author information

1
Division of Gastrointestinal Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Shizuoka, 411-8777, Japan. t.yokota@scchr.jp.
2
Department of Otolaryngology-Head and Neck Surgery, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan.
3
Department of Medical Oncology, The Cancer Institute Hospital of JFCR, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.
4
Department of Otolaryngology, Center of Head and Neck Surgery, Tokai University, 143 Shimokasuya, Isehara, Japan.
5
Department of Otolaryngology, Head and Neck Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, 537-8511, Japan.
6
Department of Medical Oncology, Kindai University Faculty of Medicine, Sayama, Osaka, 589-0014, Japan.
7
Department of Head and Neck Cancer, Hyogo Cancer Center, Akashi, 673-8558, Japan.
8
Department of Otolaryngology-Head and Neck Surgery, Nara Medical University, Kashiharashi, 634-8522, Japan.
9
Department of Otorhinolaryngology-Head and Neck Surgery, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
10
Department of Head and Neck Surgery, Shikoku Cancer Center, Matsuyama, 791-0280, Japan.
11
Department of Head and Neck Surgery, Miyagi Cancer Center, 47-1 Medeshimashiote, Natori, 981-1293, Japan.
12
Department of Otorhinolaryngology, Jikei University School of Medicine, 3-19 Nishi-Shinbashi, Minato-ku, Tokyo, 105-0003, Japan.
13
Medical Oncology, Nara Hospital, Kindai University School of Medicine, 1248-1 Otoda-cho, Ikoma, Nara, 630-0293, Japan.
14
Head and Neck, Chiba Cancer Center, 666-2 Nitona-cho, Chuo-ku, Chiba, 260-0801, Japan.
15
Department of Otorhinolaryngology, Nagoya University, Graduate School of Medicine, 65 Tsurumai-cho, Shouwa-ku, Nagoya, Aichi, 466-8550, Japan.
16
Department of Head and Neck Surgery, Aichi Cancer Center Hospital and Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.
17
Division of Head and Neck Surgery, Saitama Cancer Center, 780 Komuro, Inamachi, Kitaadachi-gun, Saitama, Japan.
18
Department of Hematology and Oncology, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama, Japan.
19
Department of Otolaryngology-Head and Neck Surgery, Kyoto University Hospital, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
20
, Headquarters of New Product Evaluation and Development, Otsuka Pharmaceutical Co., Ltd., Shinagawa Grand Central Tower, 2-16-4 Konan, Minato-ku, Tokyo, 108-8242, Japan.
21
Department of Otolaryngology, Eiju General Hospital, 2-23-16 Higashiueno, Taito-ku, Tokyo, 110-8645, Japan.
22
Department of Head and Neck Medical Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.

Abstract

BACKGROUND:

Recent 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).

METHODS:

Patients 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.

RESULTS:

From 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.

CONCLUSIONS:

The 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 REGISTRATION:

ClinicalTrials.gov under the identifier NCT02085460 (the date of trial registration: March 11, 2014).

KEYWORDS:

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

PMID:
28476132
PMCID:
PMC5420134
DOI:
10.1186/s12885-017-3295-4
[Indexed for MEDLINE]
Free PMC Article

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