Olanzapine for the Treatment of Advanced Cancer-Related Chronic Nausea and/or Vomiting: A Randomized Pilot Trial

Abstract

Importance: Nausea and vomiting, unrelated to chemotherapy, can be substantial symptoms in patients with advanced cancer.

Objective: To evaluate the utility of olanzapine for treating chronic nausea/vomiting, unrelated to chemotherapy, in patients with advanced cancer.

Design, setting, and participants: This study is a double-line, placebo-controlled, randomized clinical trial conducted from July 2017 through April 2019, with analysis conducted in 2019. Eligible participants were outpatients with advanced cancer who had persistent nausea/vomiting without having had chemotherapy or radiotherapy in the prior 14 days. Chronic nausea was present for at least 1 week (worst daily nausea numeric rating scores needed to be greater than 3 on a 0-10 scale).

Interventions: Patients received olanzapine (5 mg) or a placebo, orally, daily for 7 days.

Main outcomes and measures: Patient-reported outcomes were used for study end points. Data were collected at baseline and daily for 7 more days. The primary study end point (the change in nausea numeric rating scores from baseline to the last treatment day) and the study hypothesis were both identified prior to data collection.

Results: A total of 30 patients (15 per arm) were enrolled; these included 16 women and 14 men who had a mean (range) age of 63 (39-79) years. Baseline median nausea scores, in all patients, were 9 out of 10 (range, 8-10). After 1 day and 1 week, the median nausea scores in the placebo arm were 9 out of 10 (range, 8-10) on both days, compared with the olanzapine arm scores of 2 out of 10 (range, 2-3) after day 1 and 1 out of 10 (range, 0-3) after 1 week. After 1 week of treatment, the reduction in nausea scores in the olanzapine arm was 8 points (95% CI, 7-8) higher than that of the placebo arm. The primary 2-sided end point P value was <.001. Correspondingly, patients in the olanzapine arm reported less emesis, less use of other antiemetic drugs, better appetite, less sedation, less fatigue, and better well-being. One patient, on the placebo, stopped treatment early owing to lack of perceived benefit. No patients receiving olanzapine reported excess sedation or any other adverse event.

Conclusions and relevance: Olanzapine, at 5 mg/d, appeared to be effective in controlling nausea and emesis and in improving other symptoms and quality-of-life parameters in the study population.

Trial registration: ClinicalTrials.gov Identifier: NCT03137121.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Le-Rademacher reported receiving grants from Mayo Clinic during the conduct of the study. Dr Albany reported receiving grants from the National Institutes of Health during the conduct of the study. Dr Loprinzi reported receiving grants from the National Cancer Institute during the conduct of the study, and personal fees from PledPharma, Disarm Therapeutics, Asahi Kasei, Metys Pharmaceuticals, OnQuality Pharmaceuticals, Mitsubishi Tanabe Pharma, and NKMax outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. CONSORT Diagram

Data regarding eligibility assessment were not collected. All entered patients received the appropriate randomly assigned intervention, and no patients were lost to follow-up. All patients were included in the analyses. aOne patient stopped the study medication on day 5 owing to nausea, which was allowed by the protocol.

Figure 2.. Plots of Daily Data Over Time

Plots with 95% CIs, regarding daily data during the study period for numeric rating score (NRS) for nausea (A), the number of emetogenic episodes per day (B), the number of rescue antiemetic doses per day (C), and NRS for well-being (D). In some plots, lower scores are better, while higher scores are better in others; in all situations, the olanzapine arm had more favorable results. The provided P values are from the Wilcoxon test in which change from baseline to day 7 was tested between arms.