According to a phase III trial reported by Navari et al in The New England Journal of Medicine, the addition of the antipsychotic agent olanzapine vs placebo to dexamethasone, aprepitant, or fosaprepitant, and a 5-hydroxytryptamine type 3–receptor antagonist reduced nausea and improved antiemetic complete response rates among patients receiving highly emetogenic chemotherapy.
In the double-blind trial, 380 evaluable patients were randomized to receive olanzapine at 10 mg or placebo daily on days 1 to 4 of chemotherapy cycles. These patients had had no previous chemotherapy and were receiving cisplatin at ≥ 70 mg/m2 or cyclophosphamide/doxorubicin. The primary endpoint was prevention of nausea. Complete response, defined as no emesis and no use of rescue medication, was a secondary endpoint.
Nausea Prevention and Complete Response
No chemotherapy-induced nausea within the first 24 hours after chemotherapy was achieved in 74% of patients in the olanzapine group vs 45% of patients in the placebo group (P = .002). Higher proportions of olanzapine patients were also free of nausea at 25 to 120 hours (42% vs 25%, P = .002) and across the overall 120-hour period (37% vs 22%, P = .002). Complete response was significantly more common with olanzapine for all three periods: 86% vs 65% (P < .001), 67% vs 52% (P = .007), and 64% vs 41% (P < .001), respectively. Severe sedation was observed in 5% of olanzapine patients on day 2 of treatment.
The investigators concluded: “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.”
The study was funded by the National Cancer Institute. ■