{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T17:34:36Z","timestamp":1784396076372,"version":"3.55.0"},"reference-count":19,"publisher":"American Medical Association (AMA)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"<jats:sec><jats:title>Importance<\/jats:title><jats:p>It is unknown whether olanzapine combined with triplet antemetic therapy is effective for all patients undergoing highly emetogenic chemotherapy. A secondary analysis of randomized clinical trials using olanzapine may provide insight into the effectiveness of olanzapine for chemotherapy-induced nausea and vomiting (CINV), including cisplatin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To examine the add-on effect of olanzapine according to risk factors for CINV.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>This preplanned secondary analysis evaluated results of the J-FORCE trial, a large double-blind, placebo-controlled phase 3 randomized clinical trial conducted in Japan from February 9, 2017, to July 18, 2018. Participants were enrolled from 26 participating hospitals across Japan and included patients aged 20 to 75 years who had a malignant tumor and were cisplatin-naive. The efficacy analysis population of the J-FORCE trial was analyzed according to allocation adjustment factors (sex [male or female], age [\u226555 years or &amp;amp;lt;55 years], and cisplatin dose [\u226570 mg\/m<jats:sup>2<\/jats:sup> or &amp;amp;lt;70 mg\/m<jats:sup>2<\/jats:sup>]) and patient-related risk factors (history of motion sickness, drinking habit [defined as alcoholic drinks consumption in excess of occasional drinking], and history of morning sickness during pregnancy). Statistical analysis was performed from February 18 to April 18, 2020.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interventions<\/jats:title><jats:p>Patients were randomized 1:1 to receive 5 mg of olanzapine or placebo combined with standard triplet antiemetic therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>The primary end point was complete response (CR, defined as no vomiting and no use of rescue medication) in the delayed phase (24-120 hours after cisplatin-based chemotherapy administration). Secondary end points were CR, complete control, and total control in the acute, delayed, and overall phases for 6 CINV risk factors as well as time to treatment failure. The CR point estimates and 95% CIs of the differences between groups were calculated, and a Mantel-Haenszel test was performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of the 705 patients (mean [SD] age, 63.0 [9.2] years; 471 males [66.8%]) included in the efficacy analysis population; 581 patients (82.4%) were 55 years or older, and 526 (74.6%) were treated with a cisplatin dose of 70 mg\/m<jats:sup>2<\/jats:sup> or more. Risk difference (RD) for a CR in the delayed phase was significantly greater in the olanzapine group than the placebo group in males (RD, 12.6% [95% CI, 5.0%-20.1%]; <jats:italic>P<\/jats:italic>\u2009=\u2009.001); in females (RD, 14.5% [95% CI, 2.2%-26.3%]; <jats:italic>P<\/jats:italic>\u2009=\u2009.02); in those 55 years or older (RD, 11.1% [95% CI, 3.9%-18.2%]; <jats:italic>P<\/jats:italic>\u2009=\u2009.003) or younger than 55 years (RD, 23.6% [95% CI, 7.3%-38.3%]; <jats:italic>P<\/jats:italic>\u2009=\u2009.005); for a cisplatin dose of 70 mg\/m<jats:sup>2<\/jats:sup> or more (RD, 13.5% [95% CI, 5.9%-21.0%]; <jats:italic>P<\/jats:italic>\u2009&amp;amp;lt;\u2009.001); for those without a history of motion sickness (RD, 13.9% [95% CI, 6.9%-20.6%]; <jats:italic>P<\/jats:italic>\u2009&amp;amp;lt;\u2009.001); for those with a drinking habit (RD, 14.9% [95% CI, 6.1%-23.4%]; <jats:italic>P<\/jats:italic>\u2009=\u2009.001) or without a drinking habit (RD, 12.0% [95% CI, 2.5%-21.3%]; <jats:italic>P<\/jats:italic>\u2009=\u2009.01); and for those with a history of morning sickness during pregnancy (RD, 27.2% [9.7%-42.6%]; <jats:italic>P<\/jats:italic>\u2009=\u2009.002). In other subgroups, a delayed CR was higher in the olanzapine group than the placebo group, although not significantly higher.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Relevance<\/jats:title><jats:p>Results of this study suggest a benefit of using 5 mg of olanzapine plus triplet antiemetic therapy to counter CINV regardless of the presence or absence of risk factors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial Registration<\/jats:title><jats:p>University Hospital Medical Information Network Clinical Trials Registry Identifier: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/center6.umin.ac.jp\/cgi-open-bin\/ctr_e\/ctr_view.cgi?recptno=R000028387\">UMIN000024676<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2023.10894","type":"journal-article","created":{"date-parts":[[2023,5,2]],"date-time":"2023-05-02T15:01:10Z","timestamp":1683039670000},"page":"e2310894","source":"Crossref","is-referenced-by-count":11,"title":["Efficacy of Olanzapine in Addition to Standard Triplet Antiemetic Therapy for Cisplatin-Based Chemotherapy"],"prefix":"10.1001","volume":"6","author":[{"given":"Masakazu","family":"Abe","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuhiro","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukiyoshi","family":"Fujita","sequence":"additional","affiliation":[{"name":"Division of Pharmacy, Gunma Prefectural Cancer Center, \u014cta, Gunma, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyasu","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Wakayama Medical University Hospital, Wakayama, Wakayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Kitagawa","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Kobe Minimally Invasive Cancer Center, Kobe, Hy\u014dgo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Inui","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuya","family":"Hirano","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Hy\u014dgo Prefectural Amagasaki General Medical Center, Amagasaki, Hy\u014dgo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukio","family":"Sakata","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Hakodate Municipal Hospital, Hakodate, Hokkaido, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotoshi","family":"Iihara","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Gifu University Hospital, Gifu, Gifu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichi","family":"Shibuya","sequence":"additional","affiliation":[{"name":"Department of Transplant Surgery, K\u014dchi Health Science Center, K\u014dchi, K\u014dchi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachi\u014dji, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiko","family":"Shibata","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Kouseiren Takaoka Hospital, Takaoka, Toyama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kensuke","family":"Hori","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Kansai Rousai Hospital, Amagasaki, Hy\u014dgo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruko","family":"Daga","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Osaka City General Hospital, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiaki","family":"Nakayama","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Saitama Cancer Center, Kitaadachi-gun, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiko","family":"Sakata","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Hiroshima City North Medical Center Asa Citizens Hospital, Hiroshima, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takako Yanai","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, National Cancer Center Hospital, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadamoto","family":"Zenda","sequence":"additional","affiliation":[{"name":"Japan Supportive, Palliative and Psychosocial Oncology Group, Tokyo, 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