A randomized, double-blind, placebo-controlled trial of olanzapine versus placebo plus ondansetron and dexamethasone for antiemetic prophylaxis in patients receiving oxaliplatin-, irinotecan-, or carboplatin-based chemotherapy

Abstract

Purpose: A two-drug regimen of palonosetron and dexamethasone is standard for moderately emetogenic chemotherapy (MEC), including oxaliplatin and irinotecan. Current guidelines recommend adding an NK1 receptor antagonist for carboplatin-based or MEC in patients with high-risk features. Given the comparable efficacy of olanzapine, this study evaluated the effectiveness of low-dose olanzapine (OLN, 5 mg) combined with ondansetron and dexamethasone in preventing chemotherapy-induced nausea and vomiting (CINV). Methods: In this double-blind, randomized controlled trial, patients initiating oxaliplatin-, carboplatin-, or irinotecan-based chemotherapy were randomized 1:1 to receive OLN or placebo on Days 1–4, with ondansetron and dexamethasone. Randomization was stratified by chemotherapy type and high-risk factors (female aged < 50 years). The primary endpoint was total protection (mild/no nausea, no vomiting, and no rescue therapy) within 120 h post-chemotherapy. Secondary endpoints included total control, complete response, nausea/vomiting severity, rescue use, adverse events, and patient satisfaction. Results: Among 139 evaluable patients, 69 received OLN and 70 received a placebo. Total protection was achieved in 71.0% of OLN patients versus 55.7% with placebo (p = 0.06). Total control was significantly higher with OLN (62.3% vs. 38.6%, p = 0.005). Delayed nausea (grade ≥ 2) occurred less frequently with OLN (13.0% vs. 30.0%, p = 0.015). Complete response and rescue use did not differ between groups. Somnolence rates were similar, but anorexia was less familiar with OLN. Notably, 95.6% of OLN patients preferred to continue the same regimen, compared with 72.9% of placebo recipients (p = 0.001). Conclusion: Olanzapine (5 mg) combined with ondansetron and dexamethasone was associated with a moderate improvement in total protection and significant improvements in no-nausea and total control rates.