Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting

Abstract

BACKGROUND We examined the efficacy of olanzapine for the prevention of nausea and vomiting in patients receiving highly emetogenic chemotherapy. METHODS In a randomized, double-blind, phase 3 trial, we compared olanzapine with placebo, in combination with dexamethasone, aprepitant or fosaprepitant, and a 5-hydroxytryptamine type 3–receptor antagonist, in patients with no previous chemotherapy who were receiving cisplatin (≥70 mg per square meter of body-surface area) or cyclophosphamide–doxorubicin. The doses of the three concomitant drugs administered before and after chemotherapy were similar in the two groups. The two groups received either 10 mg of olanzapine orally or matching placebo daily on days 1 through 4. Nausea prevention was the primary end point; a complete response (no emesis and no use of rescue medication) was a secondary end point. RESULTS In the analysis, we included 380 patients who could be evaluated (192 assigned to olanzapine, and 188 to placebo). The proportion of patients with no chemotherapy-induced nausea was significantly greater with olanzapine than with placebo in the first 24 hours after chemotherapy (74% vs. 45%, P = 0.002), the period from 25 to 120 hours after chemotherapy (42% vs. 25%, P = 0.002), and the overall 120-hour period (37% vs. 22%, P = 0.002). The complete-response rate was also significantly increased with olanzapine during the three periods: 86% versus 65% (P<0.001), 67% versus 52% (P = 0.007), and 64% versus 41% (P<0.001), respectively. Although there were no grade 5 toxic effects, some patients receiving olanzapine had increased sedation (severe in 5%) on day 2. CONCLUSIONS Olanzapine, as compared with placebo, significantly improved nausea prevention, as well as the complete-response rate, among previously untreated patients who were receiving highly emetogenic chemotherapy. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02116530.)

Prevention of chemotherapy-induced nausea: the role of neurokinin-1 (NK1) receptor antagonists

“…The benefit of adding olanzapine to a triplet aprepitant/fosaprepitant–5-HT 3 RA–dexamethasone regimen for the control of nausea has been evaluated in a phase III study in 380 patients receiving cisplatin- or AC-based HEC [77]. Nausea prophylaxis was the primary endpoint.…”

Chronic Unexplained Nausea and Vomiting or Gastric Neuromuscular Dysfunction (GND)? An Update on Nomenclature, Pathophysiology and Treatment, and Relationship to Gastroparesis

“…Finally, olanzapine, a 5-HT 2 , 5-HT 3 , D2, M 1 , M 3 , H 1 , and alpha-2 receptor antagonist, has also been used for patients with nausea and vomiting; however, efficacy studies have only been performed in chemotherapy and palliative care trials. 18–20 …”

Efficacy of triple antiemetic therapy (palonosetron, dexamethasone, aprepitant) for chemotherapy-induced nausea and vomiting in patients receiving carboplatin-based, moderately emetogenic chemotherapy

“…Olanzapine is another antipsychotic drug whose effect is manifested through blockade of multiple neurotransmitter receptors. Navari et al (2016) reported on a randomized, double-blind, phase-3 trial comparing olanzapine with placebo, in combination with dexamethasone, aprepitant or fosaprepitant, and 5-HT3 receptor antagonist in patients receiving cisplatin or AC. Olanzapine significantly improved nausea prevention, as well as the prevalence of a CR, among patients receiving HEC.…”