Abstract
BACKGROUND: Chemotherapy-induced nausea and vomiting is a common adverse event of cancer treatments. Despite prophylactic antiemetic treatment, nausea remains a particular problem. We aimed to identify risk factors and clarify the usefulness of olanzapine for the control of carboplatin-induced nausea. METHODS: This was a pooled analysis of data from a single-arm, open-label, phase II trial and a prospective, randomized, double-blind, placebo-controlled phase III trial. We combined data from two trials with similar inclusion and exclusion criteria and treatment schedules. Chemotherapy-naïve patients aged ≥ 20 years with solid cancers who were scheduled to receive a first course of carboplatin-containing chemotherapy were enrolled. Patients in the olanzapine and placebo groups received olanzapine 5 mg or placebo, respectively, in combination with the neurokinin-1 (NK(1)) receptor antagonist aprepitant, a 5-hydroxytryptamine-3 (5-HT(3)) receptor antagonist, and dexamethasone. Olanzapine was administered on days 1-4 after the evening meal. The primary endpoint was the proportion of patients without nausea in the overall phase (0-120 h). Intergroup differences and their 95% confidence intervals (CIs) were estimated in each phase and population. Univariable and multivariable logistic regression analyses were performed to determine the risk factors associated with nausea, appetite loss, and complete response (no vomiting and no rescue medication use) rate. Odds ratios (ORs), 95% CIs, and p-values for each background factor were calculated. RESULTS: A total of 388 patients were evaluated (79.4% male, median age 72 years), including 208 patients in the olanzapine group. Overall, 87.5% in the olanzapine group and 75.0% in the placebo group were free of nausea (intergroup difference 12.5%, 95% CI, 4.7-20.3, p = 0.002), and the difference in proportion of patients reporting no appetite loss was 20.6% (95% CI, 11.5-29.6, p < 0.001). The overall complete response rates were 88.0% in the olanzapine group and 80.6% in the placebo group (p = 0.049). Multivariable analysis only identified no olanzapine use as significantly associated with a decreased risk of nausea (adjusted OR, 0.45, 95% CI, 0.26-0.76). CONCLUSIONS: This analysis revealed that adding olanzapine to triple antiemetic therapy was associated with improved control of carboplatin-induced nausea. TRIAL REGISTRATION: The trial was registered with the University Hospital Medical Information Network Clinical Trial Registry (UMIN) 000026739, registered on 1 April 2017 and 000037749, registered on 1 September 2019.