{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T16:08:53Z","timestamp":1790179733151,"version":"4.1.0"},"reference-count":13,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Capture of Outstanding Clinical Research and Evolution"},{"DOI":"10.13039\/501100005731","name":"Juntendo University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Olanzapine 5\u2009mg improves chemotherapy-induced nausea and vomiting (CINV) control in patients receiving anthracycline\u2013cyclophosphamide (AC) chemotherapy, but sedation remains a concern. We evaluated whether central nervous system (CNS) symptom burden identifies patients at higher risk of poor CINV control.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and methods<\/jats:title>\n                    <jats:p>This secondary analysis of the phase III JTOP-B trial included women with breast cancer receiving AC chemotherapy. Patients were randomized to olanzapine 5\u2009mg or placebo plus standard triplet antiemetic therapy. Daily patient-reported sedation and concentration impairment were assessed for 5\u2009days. CNS burden was evaluated using recurrent \u201cBad Days\u201d (concurrent moderate\/severe sedation and concentration impairment) and cumulative CNS burden scores. Associations between CNS symptom patterns and complete response (CR; no emesis and no rescue medication) during 0-120\u2009hours were analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 480 patients, CR rates decreased with increasing CNS symptom severity in both groups. In the olanzapine group, CR rates decreased across increasing sedation (75.0%-51.6%) and concentration impairment (78.1%-48.6%). Concentration impairment more strongly identified patients with poor CINV control than sedation alone. Higher cumulative CNS burden and recurrent Bad Days were associated with lower CR rates, identifying a clinically vulnerable population. Olanzapine maintained higher CR rates than placebo across CNS symptom strata.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CNS symptom burden was associated with suboptimal CINV control, while 5\u2009mg of olanzapine maintained superior antiemetic efficacy across CNS symptom strata. Monitoring day-to-day CNS symptoms may help identify patients requiring closer observation or additional supportive care.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>Japan Registry of Clinical Trials Identifier: jRCT1031200134<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/oncolo\/oyag351","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T11:33:50Z","timestamp":1788867230000},"source":"Crossref","is-referenced-by-count":0,"title":["Central nervous system symptom burden and clinical implications for antiemetic management with olanzapine in AC chemotherapy"],"prefix":"10.1093","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2171-0474","authenticated-orcid":false,"given":"Ryoko","family":"Udagawa","sequence":"first","affiliation":[{"name":"Department of Pharmacy, National Cancer Center Hospital , Chuo, Tokyo, 104-0045,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8140-4565","authenticated-orcid":false,"given":"Mototsugu","family":"Shimokawa","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Yamaguchi University Graduate School of Medicine , Ube, Yamaguchi, 755-8505,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4171-454X","authenticated-orcid":false,"given":"Hirotoshi","family":"Iihara","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Gifu University Hospital , Gifu, Gifu, 501-1194,","place":["Japan"]},{"name":"Cancer Center, Gifu University Hospital , Gifu, Gifu, 501-1194,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2431-7403","authenticated-orcid":false,"given":"Rie","family":"Ozeki","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Juntendo University , Urayasu, Chiba, 279-0013,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiko","family":"Tsuneizumi","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Shizuoka General Hospital , Shizuoka, Shizuoka, 420-8527,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5622-8352","authenticated-orcid":false,"given":"Manabu","family":"Futamura","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Gifu University Hospital , Gifu, Gifu, 501-1194,","place":["Japan"]},{"name":"Department of Breast Surgery, Gifu University Hospital , Gifu, Gifu, 501-1194,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Fujita","sequence":"additional","affiliation":[{"name":"Department of Breast Oncology, Juntendo Urayasu Hospital , Urayasu, Chiba, 279-0021,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideaki","family":"Ogata","sequence":"additional","affiliation":[{"name":"Department of Breast and Endocrine Surgery, Toho University Medical Center Omori Hospital , Ota, Tokyo, 143-8541,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7361-3647","authenticated-orcid":false,"given":"Hiroko","family":"Bando","sequence":"additional","affiliation":[{"name":"Department of Breast and Endocrine Surgery, Institute of Medicine, University of Tsukuba , Tsukuba, Ibaraki, 305-8575,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshitaka","family":"Uomori","sequence":"additional","affiliation":[{"name":"Department of Breast Oncology, Faculty of Medicine, Juntendo University , Bunkyo, Tokyo, 113-8421,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5907-5547","authenticated-orcid":false,"given":"Hironobu","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, National Cancer Center Hospital , Chuo, Tokyo, 104-0045,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryosuke","family":"Hayami","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Shizuoka General Hospital , Shizuoka, Shizuoka, 420-8527,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2481-7739","authenticated-orcid":false,"given":"Yoshihisa","family":"Tokumaru","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Gifu University Hospital , Gifu, Gifu, 501-1194,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4557-5126","authenticated-orcid":false,"given":"Goro","family":"Kutomi","sequence":"additional","affiliation":[{"name":"Department of Breast Oncology, Faculty of Medicine, Juntendo University , Bunkyo, Tokyo, 113-8421,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7624-7611","authenticated-orcid":false,"given":"Kan","family":"Yonemori","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, National Cancer Center Hospital , Chuo, Tokyo, 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