{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:29:39Z","timestamp":1782779379622,"version":"3.54.5"},"reference-count":17,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2022,3,2]],"date-time":"2022-03-02T00:00:00Z","timestamp":1646179200000},"content-version":"unspecified","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Capture of Outstanding Clinical Research and Evolution (CORE\uff09project at Juntendo University","award":["CORE-R1-01"],"award-info":[{"award-number":["CORE-R1-01"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>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\u2009mg or 10\u2009mg 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\u2009mg.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and analysis<\/jats:title><jats:p>To assess whether 5\u2009mg 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\u2009hours after the initiation of chemotherapy. Treatment group comparison for the primary endpoint will be done by using the Cochran-Mantel-Haenszel test.<\/jats:p><\/jats:sec><jats:sec><jats:title>Ethics and dissemination<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial registration number<\/jats:title><jats:p>Japan Registry of Clinical Trials (jRCT) jRCT1031200134; protocol date: 30 July 2020, version: 1.3, approval: 25 August 2020.<\/jats:p><\/jats:sec>","DOI":"10.1136\/bmjopen-2021-058755","type":"journal-article","created":{"date-parts":[[2022,3,2]],"date-time":"2022-03-02T16:08:18Z","timestamp":1646237298000},"page":"e058755","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["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)"],"prefix":"10.1136","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2431-7403","authenticated-orcid":false,"given":"Rie","family":"Ozeki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4171-454X","authenticated-orcid":false,"given":"Hirotoshi","family":"Iihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mototsugu","family":"Shimokawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironobu","family":"Hashimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masakazu","family":"Abe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Mukohara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroko","family":"Bando","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshinobu","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Kawazoe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayo","family":"Komoda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takako","family":"Yanai Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsue","family":"Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2022,3,2]]},"reference":[{"key":"2023030803132607000_12.3.e058755.1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200005253422102"},{"key":"2023030803132607000_12.3.e058755.2","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2017.0117"},{"key":"2023030803132607000_12.3.e058755.3","doi-asserted-by":"crossref","first-page":"3240","DOI":"10.1200\/JCO.2017.74.4789","article-title":"Antiemetics: American Society of clinical oncology clinical practice guideline update","volume":"35","author":"Hesketh","year":"2017","journal-title":"J Clin Oncol"},{"key":"2023030803132607000_12.3.e058755.4","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdw270"},{"key":"2023030803132607000_12.3.e058755.5","doi-asserted-by":"publisher","DOI":"10.1007\/s10147-015-0852-1"},{"key":"2023030803132607000_12.3.e058755.6","doi-asserted-by":"crossref","first-page":"3319","DOI":"10.1002\/cam4.2979","article-title":"A double-blind, randomized, multicenter phase 3 study of palonosetron vs granisetron combined with dexamethasone and fosaprepitant to prevent chemotherapy-induced nausea and vomiting in patients with breast cancer receiving anthracycline and cyclophosphamide","volume":"9","author":"Matsumoto","year":"2020","journal-title":"Cancer Med"},{"key":"2023030803132607000_12.3.e058755.7","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1200\/JCO.2017.74.4375","article-title":"Placebo-Controlled, double-blinded phase III study comparing dexamethasone on day 1 with dexamethasone on days 1 to 3 with combined neurokinin-1 receptor antagonist and palonosetron in High-Emetogenic chemotherapy","volume":"36","author":"Ito","year":"2018","journal-title":"J Clin Oncol"},{"key":"2023030803132607000_12.3.e058755.8","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1056\/NEJMoa1515725","article-title":"Olanzapine for the prevention of chemotherapy-induced nausea and vomiting","volume":"375","author":"Navari","year":"2016","journal-title":"N Engl J Med"},{"key":"2023030803132607000_12.3.e058755.9","unstructured":"NCCN clinical practice guidelines in oncology: antiemesis version 1, 2021. Available: https:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/antiemesis.pdf [Accessed 24 Dec 2021]."},{"key":"2023030803132607000_12.3.e058755.10","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.01296"},{"key":"2023030803132607000_12.3.e058755.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpainsymman.2013.05.003"},{"key":"2023030803132607000_12.3.e058755.12","doi-asserted-by":"publisher","DOI":"10.1007\/s00520-015-2829-z"},{"key":"2023030803132607000_12.3.e058755.13","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1093\/jjco\/hyx084","article-title":"A phase II study of palonosetron, aprepitant, dexamethasone and olanzapine for the prevention of cisplatin-based chemotherapy-induced nausea and vomiting in patients with thoracic malignancy","volume":"47","author":"Nakashima","year":"2017","journal-title":"Jpn J Clin Oncol"},{"key":"2023030803132607000_12.3.e058755.14","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1007\/s10147-017-1200-4","article-title":"A double-blind randomized phase II dose-finding study of olanzapine 10\u00a0mg or 5\u00a0mg for the prophylaxis of emesis induced by highly emetogenic cisplatin-based chemotherapy","volume":"23","author":"Yanai","year":"2018","journal-title":"Int J Clin Oncol"},{"key":"2023030803132607000_12.3.e058755.15","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.2217\/fon-2020-0834","article-title":"Low-dose olanzapine, sedation and chemotherapy-induced nausea and vomiting: a prospective randomized controlled study","volume":"17","author":"Mukhopadhyay","year":"2021","journal-title":"Future Oncol"},{"key":"2023030803132607000_12.3.e058755.16","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/S1470-2045(19)30678-3","article-title":"Olanzapine 5 Mg plus standard antiemetic therapy for the prevention of chemotherapy-induced nausea and vomiting (J-FORCE): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial","volume":"21","author":"Hashimoto","year":"2020","journal-title":"Lancet Oncol"},{"key":"2023030803132607000_12.3.e058755.17","unstructured":"Cancer information services, National cancer center, Japan. Available: https:\/\/ganjoho.jp\/reg_stat\/statistics\/data\/dl\/en.html [Accessed 24 Dec 2021]."}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2021-058755","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T12:08:14Z","timestamp":1678277294000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2021-058755"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3]]},"references-count":17,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,3,28]]},"published-print":{"date-parts":[[2022,3]]}},"alternative-id":["10.1136\/bmjopen-2021-058755"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2021-058755","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3]]}}}