start-ver=1.4
cd-journal=joma
no-vol=17
cd-vols=
no-issue=1
article-no=
start-page=314
end-page=322
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2017
dt-pub=20170505
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=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
en-subtitle=
kn-subtitle=
en-abstract=
kn-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).
en-copyright=
kn-copyright=

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en-aut-name=NishimoriHisakazu
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en-aut-name=NakaY.
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affil-num=1
en-affil=Division of Gastrointestinal Oncology, Shizuoka Cancer Center
kn-affil=

affil-num=2
en-affil=Department of Otolaryngology-Head and Neck Surgery, Tohoku University Graduate School of Medicine
kn-affil=

affil-num=3
en-affil=Department of Medical Oncology, The Cancer Institute Hospital of JFCR
kn-affil=

affil-num=4
en-affil=Department of Otolaryngology, Center of Head and Neck Surgery, Tokai University
kn-affil=

affil-num=5
en-affil=Department of Otolaryngology, Head and Neck Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases
kn-affil=

affil-num=6
en-affil=Department of Medical Oncology, Kindai University Faculty of Medicine
kn-affil=

affil-num=7
en-affil=Department of Head and Neck Cancer, Hyogo Cancer Center
kn-affil=

affil-num=8
en-affil=Department of Otolaryngology-Head and Neck Surgery, Nara Medical University
kn-affil=

affil-num=9
en-affil=Department of Otorhinolaryngology-Head and Neck Surgery, Hiroshima University Hospital
kn-affil=

affil-num=10
en-affil=Department of Head and Neck Surgery, Shikoku Cancer Center
kn-affil=

affil-num=11
en-affil=Department of Head and Neck Surgery, Miyagi Cancer Center
kn-affil=

affil-num=12
en-affil=Department of Otorhinolaryngology, Jikei University School of Medicine
kn-affil=

affil-num=13
en-affil= Medical Oncology, Nara Hospital, Kindai University School of Medicine
kn-affil=

affil-num=14
en-affil=Head and Neck, Chiba Cancer Center
kn-affil=

affil-num=15
en-affil=Department of Otorhinolaryngology, Nagoya University, Graduate School of Medicine
kn-affil=

affil-num=16
en-affil=Department of Head and Neck Surgery, Aichi Cancer Center Hospital and Research Institute
kn-affil=

affil-num=17
en-affil=Division of Head and Neck Surgery, Saitama Cancer Center
kn-affil=

affil-num=18
en-affil=Department of Hematology and Oncology, Okayama University Hospital
kn-affil=

affil-num=19
en-affil=Department of Otolaryngology-Head and Neck Surgery, Kyoto University Hospital
kn-affil=

affil-num=20
en-affil= Headquarters of New Product Evaluation and Development, Otsuka Pharmaceutical Co., Ltd.
kn-affil=

affil-num=21
en-affil= Headquarters of New Product Evaluation and Development, Otsuka Pharmaceutical Co., Ltd.
kn-affil=

affil-num=22
en-affil=Department of Otolaryngology, Eiju General Hospital
kn-affil=

affil-num=23
en-affil=Department of Head and Neck Medical Oncology, National Cancer Center Hospital East
kn-affil=
en-keyword=Chemoradiotherapy
kn-keyword=Chemoradiotherapy
en-keyword=Head and neck cancer
kn-keyword=Head and neck cancer
en-keyword=Oral mucositis
kn-keyword=Oral mucositis
en-keyword=Placebo-controlled
kn-keyword=Placebo-controlled
en-keyword=Randomized
kn-keyword=Randomized
en-keyword=Rebamipide liquid
kn-keyword=Rebamipide liquid
END