TY - JOUR
T1 - Efficacy and safety of rebamipide liquid for chemoradiotherapy-induced oral mucositis in patients with head and neck cancer
T2 - A multicenter, randomized, double-blind, placebo-controlled, parallel-group phase II study
AU - Yokota, T.
AU - Ogawa, T.
AU - Takahashi, S.
AU - Okami, K.
AU - Fujii, T.
AU - Tanaka, K.
AU - Iwae, S.
AU - Ota, I.
AU - Ueda, T.
AU - Monden, N.
AU - Matsuura, K.
AU - Kojima, H.
AU - Ueda, S.
AU - Sasaki, K.
AU - Fujimoto, Y.
AU - Hasegawa, Y.
AU - Beppu, T.
AU - Nishimori, H.
AU - Hirano, S.
AU - Naka, Y.
AU - Matsushima, Y.
AU - Fujii, M.
AU - Tahara, M.
N1 - Funding Information:
Medical writing and editorial support was provided by Dr. Keyra Martinez Dunn (Edanz Group Japan K.K.) and by ELMCOM™. The authors would also like to acknowledge the participation of Dr. Takao Ueno from the Department of General Internal Medicine, Dentistry, Oncologic Emergency, National Cancer Center Hospital, Tokyo, Japan; Dr. Sadamoto Zenda from the Division of Radiation Oncology and Particle Therapy, National Cancer Center Hospital East, Chiba, Japan; Dr. Tetsuhito Konishi from the Department of Dentistry, National Cancer Center Hospital East, Chiba, Japan; Dr. Takashi Yurikusa from the Dental and Oral Surgery, Shizuoka Cancer Center, Shizuoka, Japan; and Dr. Takeshi Kodaira from the Department of Radiation Oncology, Aichi Cancer Center Hospital and Research Institute, Nagoya, Japan. These five doctors were responsible for centrally reviewing data from each participating site.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/5/5
Y1 - 2017/5/5
N2 - 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 20-75years 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).
AB - 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 20-75years 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).
KW - Chemoradiotherapy
KW - Head and neck cancer
KW - Oral mucositis
KW - Placebo-controlled
KW - Randomized
KW - Rebamipide liquid
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U2 - 10.1186/s12885-017-3295-4
DO - 10.1186/s12885-017-3295-4
M3 - Article
C2 - 28476132
AN - SCOPUS:85018789347
VL - 17
JO - BMC Cancer
JF - BMC Cancer
SN - 1471-2407
IS - 1
M1 - 314
ER -