Study protocol for a double-blind, comparative, randomised Japanese trial of triplet standard antiemetic therapies with or without 5 mg olanzapine to prevent chemotherapy-induced nausea and vomiting for patients with breast cancer treated with an anthracycline/cyclophosphamide regimen (JTOP-B).

INTRODUCTION: Triple antiemetic therapy with neurokinin-1 receptor antagonist, 5-hydroxytryptamine type 3 receptor antagonist, and dexamethasone has been widely recommended for high emetogenic chemotherapeutic (HEC) agents and regimens, including anthracycline combined with cyclophosphamide (AC). The addition of olanzapine (OLZ) 5 mg or 10 mg to the recommended triple antiemetic therapy has demonstrated superiority in antiemetic efficacy compared with the standard triplet therapy for a cisplatin-based HEC regimen. Although OLZ plus the triple antiemetic treatment may also be effective for patients on an AC-based HEC regimen, no study has investigated its efficacy at a lower dose of 5 mg. METHODS AND ANALYSIS: To assess whether 5 mg OLZ, as compared with placebo, in combination with triple combination therapy, significantly improves nausea and vomiting, we are conducting a randomised, parallel-group controlled clinical trial with a total of 500 patients at 15 study centres in Japan. The primary outcome is the complete response rate, defined as no emetic episodes and no use of rescue medication during 120 hours after the initiation of chemotherapy. Treatment group comparison for the primary endpoint will be done by using the Cochran-Mantel-Haenszel test. ETHICS AND DISSEMINATION: The study was approved by the institutional review board of Juntendo University Hospital and relevant approval was obtained from all participating centres. All participants will be required to provide written informed consent. The trial results will be reported at conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: Japan Registry of Clinical Trials (jRCT) jRCT1031200134; protocol date: 30 July 2020, version: 1.3, approval: 25 August 2020.

Effects of a Rebamipide Mouthwash on Stomatitis Caused by Cancer Chemotherapy-Evaluation of the Efficacy by Patients Themselves.

Anticancer drug-induced stomatitis develops in 30% to 40% of cancer cases that undergo chemotherapy. However, medications for this condition are not commercially available in Japan. Upon obtaining approval of the ethics committee, a mouthwash containing rebamipide as the active ingredient (rebamipide mouthwash) was administered to one inpatient and four outpatients, who had developed stomatitis caused by cancer chemotherapy. Starting from 14 d after the administration of the rebamipide mouthwash, the patients scored a stomatitis survey on oral state, pain level, and diet and recorded the number of times they gargled, as well as any stomatitis observations, in a stomatitis diary. The total scores for the points for each of the three types of survey sections were classified into Grades 0 to 4 and evaluated as a stomatitis evaluation score (SES). The SES became "0" in three out of the five patients within 14 d of treatment. No change in SES was found in one patient. In the remaining patients, SES became "0" once but increased again later. Using image analysis software (ImageJ), the area at which the stomatitis was observed was measured. When comparing SES and change in the area in patients who agreed to participate, gradual reductions in the extent of stomatitis was observed even during the period when SES did not change. Having patients fill in an observation chart was effective for grasping changes in symptoms in outpatients.