Comparison of Mirtazapine versus Olanzapine for the Prevention of Chemotherapy-induced Nausea and Vomiting in Highly Emetogenic Chemotherapy: A Double-blind Randomized Crossover Trial
Abstract
A BSTRACT Chemotherapy-induced nausea and vomiting (CINV) is a distressing complication of chemotherapy. It can compromise treatment adherence and impair patients’ quality of life. Despite guideline-recommended drug prophylaxis, many patients still suffer from CINV. This double-blind, randomized crossover clinical trial aims to compare the safety and efficacy of mirtazapine versus olanzapine among patients treated with highly emetogenic chemotherapy (HEC). Sixty patients undergoing anthracycline-cyclophosphamide (AC) or cisplatin-containing regimen were enrolled. Half of the patients received olanzapine (5 mg/day) plus mirtazapine placebo during cycle 1, followed by mirtazapine (15 mg/day) plus olanzapine placebo in cycle 2 on days 1–4 after chemotherapy. The other half of the patients received the reverse order. Furthermore, all patients received a triplet antiemetic regimen consisting of aprepitant, granisetron, and dexamethasone. The endpoints included rate of complete control (CC), complete response, severity of nausea and vomiting based on NCI-CTCAE, visual analog scale nausea score, and adverse effects across the acute, delayed, and overall phases during the first two cycles of chemotherapy. Patients’ quality of life affected by CINV was assessed using the Functional Living Index-Emesis questionnaire. Overall CC was 56.7% for olanzapine and 53.6% for mirtazapine in cycle 1 ( P = 0.813) and 54.5% for mirtazapine and 56.3% for olanzapine in cycle 2 ( P = 0.917). The overall CC rate did not differ significantly between olanzapine and mirtazapine (odds ratio = 1.14, 95% confidence interval 0.89–1.35, P = 0.31). Similar findings were observed across all other evaluated outcomes. Sedation was the most common adverse effect. No significant difference was observed between olanzapine and mirtazapine ( P = 0.563 for the first cycle and 0.061 for the second cycle). Our findings support that mirtazapine may have comparable outcomes with olanzapine in preventing CINV following HEC.