Olanzapine may reduce nausea symptoms for patients on chemotherapy

1. Olanzapine, in addition to 3 other anti-nausea agents, significantly reduced patient’s nausea over the first 120 hours following their initial chemotherapy treatment compared to the 3 other agents alone.

2. Patients reported increased levels of sedation 2 days after their initial chemotherapy treatment, though there was no statistical difference in reported sedation between the olanzapine and placebo group from days 3-6 following chemotherapy.

Evidence Rating: 1 (Excellent)

Study Rundown: Some of the major side effects of chemotherapy which can significantly impact a patient’s treatment experience are nausea and vomiting. Though many medications have been developed and are utilized to mitigate these side effects, they are not uniformly effective. Olanzapine, an antipsychotic agent that acts on numerous receptors in the CNS involved in sensation of nausea, has led some to believe it can be effective for patients on highly emetogenic chemotherapy.

Patients receiving chemotherapy for the first time were included in this study to determine if olanzapine could reduce their symptoms of nausea. Two groups of patients were treated with 3 anti-nausea medications. One group additionally received olanzapine, while the other was given a placebo. The main outcome was complete response (no symptoms of nausea and no vomiting) over the first 120 hours after chemotherapy, and over the 0-24 and 25-120 hour periods. Secondary outcomes were assessing nausea control and side effects of olanzapine. The group treated with olanzapine had significantly greater rates of complete nausea avoidance for all 3 time periods assessed. Additionally, rates of nausea control were significantly greater for all 3 time periods.

Click to read the study, published today in NEJM

Relevant Reading: Olanzapine for chemotherapy-induced nausea and vomiting: a systematic review

In-Depth [randomized controlled study]: This study was a multicenter, randomized, double-blind, phase 3 trial. In this study 186 patients were randomized in the olanzapine group and 183 patients were randomized in the placebo group. Patients were included in the study if they were 18 years or older, had not received chemotherapy before, had a European Cooperative Oncology Group (ECOG) score of 0-2 out of 5 (low scores mean no symptoms), and met various other inclusion criteria. Both groups received what was determined to be a highly emetogenic treatment (70+ mg/m² of cisplatin, or 60 mg/m² of doxorubicin plus 600 mg/m² of cyclophosphamide). Both groups (olanzapine and placebo) were treated with a 5-HT₃ receptor antagonist, dexamethasone, and an NK₁ receptor antagonist as standard anti-emetic agents. Olanzapine was given at 10mg/day for the first 4 days following initial chemotherapy.

Percentages of patients with complete response (no nausea or vomiting) was significantly greater for the olanzapine group over all 3 time periods (1-120 hr: 64% vs 41%, 0-24 hr: 86% vs 65%, 25-120 hr: 67% vs 52%, p < 0.05 for all periods). Percentages of patients with controlled nausea (<3 on a 0-10 scale, 10 being worse nausea symptoms) was significantly greater for the olanzapine group in all 3 time periods (1-120 hr: 67% vs 49%, 0-24 hr: 87% vs 70%, 25-120 hr: 72% vs 55%, p < 0.007 for all periods). The olanzapine group had significantly higher rates of sedation reported on day 2 post chemotherapy, and from days 3-6 patients had similar rates of sedation in both olanzapine and placebo groups. This study did not investigate how different doses of olanzapine may effect nausea/vomiting, but does provide evidence for improved prevention of side effects in patients undergoing chemotherapy.

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