The post hoc analysis comparing the severity grades of chemoradiotherapy-induced oral mucositis scored between the central and local assessors in a multicenter, randomized controlled trial of rebamipide for head and neck cancer

Takao Ueno, Sadamoto Zenda, Tetsuhito Konishi, Takashi Yurikusa, Yoshiyuki Shibasaki, Hisashi Nagamoto, Masato Fujii, Takao Ueno, Sadamoto Zenda, Tetsuhito Konishi, Takashi Yurikusa, Yoshiyuki Shibasaki, Hisashi Nagamoto, Masato Fujii

Abstract

Background: In the treatment of head and neck cancer, severity of chemoradiotherapy-induced oral mucositis has been recognized as one of the key factors affecting the outcomes of the anticancer therapies. Therefore, the development of treatments mitigating oral mucositis would be of clinical significance, although the adequate assessment procedure for efficacy evaluation remains to be established. We conducted this post hoc study to assess the effect of objective evaluation of the severity grade on the outcomes of the clinical trial.

Methods: In the original trial with rebamipide liquids (0, 2, and 4%) for chemoradiotherapy-induced oral mucositis, the investigators in local sites and independent central review separately determined the severity grades in accordance with Common Terminology Criteria of Adverse Events version 3.0 based on the Assessment Sheet scored by the investigators. The discordance in severity grades between the investigators and central review was analyzed on cross table.

Results: The analysis revealed the discordance rate over the trial was 34%. While the incidences of severe oral mucositis in the placebo, rebamipide 2%, and 4% groups evaluated by the central review were 39%, 29%, and 25%, respectively, the respective values in the investigator's evaluation were 32%, 39%, and 44%.

Conclusion: In the clinical trial for the treatment of oral mucositis, it was strongly suggested that objective evaluation with a consistent scale would be required.

Keywords: Chemoradiotherapy-induced oral mucositis; Common Terminology Criteria for Adverse Events (CTCAE) version 3.0; Head and neck cancer; Independent central review; Post hoc analysis; Rebamipide liquid.

Conflict of interest statement

HN and YS are employees of the sponsor, Otsuka Pharmaceutical Co., Ltd. (Tokyo, Japan), and other authors declare that there are no conflicts of interest relevant to this manuscript.

Figures

Fig. 1
Fig. 1
Pre-fixed 10 separate sites for evaluation of clinical examination in oral mucositis. On every evaluation day, the investigator at each local site observed all pre-fixed 10 separate sites (A1–D2) in the oral cavity of patients. They checked them with the score of “0”–“88” mentioned in “Oral Mucositis Assessment Sheet”, and filled the respective boxes
Fig. 2
Fig. 2
Comparison of the severity grades of clinical examination. The graph demonstrates the incidence of grade ≥ 3 oral mucositis based on clinical examination evaluated by the independent central review (shaded columns) or the investigators in local sites (open columns)
Fig. 3
Fig. 3
The discordance rates in the respective dosing groups. The discordance number of the respective dosing groups was divided by the respective number of patients

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