Central Nervous System Symptom Burden and Clinical Implications for Antiemetic Management with Olanzapine in AC Chemotherapy

BACKGROUND: Olanzapine 5 mg improves chemotherapy-induced nausea and vomiting (CINV) control in patients receiving anthracycline-cyclophosphamide (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. PATIENTS AND METHODS: This secondary analysis of the phase III JTOP-B trial included women with breast cancer receiving AC chemotherapy. Patients were randomized to olanzapine 5 mg or placebo plus standard triplet antiemetic therapy. Daily patient-reported sedation and concentration impairment were assessed for 5 days. CNS burden was evaluated using recurrent "Bad Days" (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 hours were analyzed. RESULTS: 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% to 51.6%) and concentration impairment (78.1% to 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. CONCLUSIONS: CNS symptom burden was associated with suboptimal CINV control, while 5 mg 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. TRIAL REGISTRATION: Japan Registry of Clinical Trials Identifier: jRCT1031200134.