# Olanzapine Plus Triple Antiemetic Therapy for the Prevention of Platinum-Based Delayed-Phase Chemotherapy-Induced Nausea and Vomiting: A Meta-Analysis

## TL;DR

Adding olanzapine to standard anti-nausea treatment improves control of delayed chemotherapy-induced nausea and vomiting, but increases side effects like dry mouth.

## Contribution

This meta-analysis demonstrates that adding olanzapine to triple antiemetic therapy significantly improves delayed-phase CINV prevention.

## Key findings

- Olanzapine plus triple therapy significantly increased delayed complete response rates compared to controls.
- The combination improved overall and acute complete response rates but increased dry mouth risk.
- The treatment reduced insomnia odds compared to standard therapy.

## Abstract

Chemotherapy-induced nausea and vomiting are common side effects of cancer treatment. Currently, the standard preventive regimen is known as “triple therapy,” yet its effectiveness remains suboptimal for some patients, particularly in managing delayed-phase chemotherapy-induced nausea and vomiting. Recent studies have shown that adding low-dose olanzapine to form a “quadruple therapy” can significantly enhance delayed-phase antiemetic efficacy. This new approach has been increasingly incorporated into international clinical guidelines. Furthermore, this successful case has opened new research avenues in “drug repurposing” and “multi-target synergistic therapy.” Future investigations are expected to extend beyond traditional antiemetics, exploring agents that act on multiple neural receptor pathways, with a growing emphasis on personalized and precision medicine strategies.

Background: Chemotherapy-induced nausea and vomiting (CINV) is a common treatment-related side effect that has a detrimental effect on the quality of life of patients with cancer and may lead to dose reductions or discontinuation of chemotherapy. This meta-analysis aims to explore the efficacy and safety of olanzapine plus triple antiemetic therapy for prevention of delayed-phase platinum-based CINV. Methods: Electronic databases (five English databases: (I) PubMed, (II) ScienceDirect, (III) The Cochrane Library, (IV) Scopus, and (V) EMBASE, and two Chinese databases: China National Knowledge Infrastructure and Wanfang Database) were searched for trials that evaluated the effectiveness and safety of olanzapine plus triple antiemetic in preventing platinum-based CINV. Efficacy was no nausea, complete control, and complete response (CR) rates in the acute, delayed, and overall phases after chemotherapy. Data were analyzed using the random effects model and fixed effects model. Results: A total of 18 trials involving 3110 patients were identified, including 9 controlled trials and 9 single-arm trials. The meta-analysis of nine studies, which showed significant heterogeneity (p = 0.002, I2 = 67%), demonstrated that the olanzapine (OLN) group had a significantly higher rate of delayed CR compared to the control group (OR: 2.33, 95% CI: 1.57–3.46, p < 0.00001). Compared with the Without OLN group, the With OLN group had a significant overall CR (OR: 2.18, 95% CI: 1.80–2.63, p < 0.00001, heterogeneity: p < 0.00001, I2 = 69%), and a significant acute CR (OR: 2.28, 95% CI: 1.45–3.58, p < 0.00001, heterogeneity: p = 0.04, I2 = 51%). The meta-analysis revealed that the With OLN group could significantly increase the risk of dry mouth compared to the Without OLN group (OR  =  2.60, 95% CI: 1.73–3.91). In terms of insomnia, the odds ratio for the With OLN group was significantly lower than that for the Without OLN group (OR = 0.60; 95% CI 0.41–0.89). Conclusions: The results of this meta-analysis provide robust evidence that adding olanzapine to standard triple therapy significantly improves the prevention of platinum-based delayed-phase CINV, a setting where current antiemetic regimens often prove suboptimal. However, it also increases the risk of certain adverse events, especially dry mouth. Clinical decisions should be made based on a thorough assessment of the therapeutic benefits and safety risks.