The efficacy and safety of the addition of olanzapine to ondansetron and dexamethasone for prevention of chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic chemotherapy.

To evaluate the efficacy and safety of the addition of olanzapine to ondansetron and dexamethasone for chemotherapy-induced nausea vomiting (CINV) prevention in patients receiving highly emetogenic chemotherapy (HEC). In this randomized, double-blind, placebo-controlled, crossover study, we randomly assigned chemotherapy-naïve patients receiving HEC to receive olanzapine or placebo in addition to ondansetron and dexamethasone. All subjects were crossed over to another treatment arm on second-cycle chemotherapy. The primary endpoint was complete response (CR) rate defined as no vomiting and no use of rescue drugs. At the first cycle, there were significantly more patients with CR in the olanzapine group than in the placebo group in overall phase (68.7% vs. 25.0%, p < 0.001), acute phase (0-24 h) (75.0% vs. 31.2%, p < 0.001) and delayed phase (24-120 h) (68.7% vs. 43.7%, p = 0.038). After crossover, there were significantly more patients with CR in the olanzapine group than in the placebo group in overall phase (67.2% vs. 25.0%, p < 0.001), acute phase (71.9% vs. 32.8%, p < 0.001) and delayed phase (67.2% vs. 37.5%, p < 0.001). In crossover analysis, the olanzapine group had significantly lower mean nausea (1.28 vs. 3.05, p < 0.001) and fatigue (3.5 vs. 4.58, p < 0.001) scores but higher mean appetite (2.5 vs. 1.55, p = 0.003) and sleepiness (3.26 vs. 2.2, p < 0.001) scores. There were no grade 3 and 4 anti-emetic-drug-related toxicities. Mean QT interval changes did not different between two groups (-4.30 vs. -1.86, p = 0.69). The addition of olanzapine to ondansetron and dexamethasone significantly improved CINV prevention and was safe in patients receiving HEC.