A double-blind randomized phase II dose-finding study of olanzapine 10mg or 5mg for the prophylaxis of emesis induced by highly emetogenic cisplatin-based chemotherapy.

Abstract

The aim of this phase II study was to evaluate the efficacy and safety of two doses (10 and 5mg) of olanzapine in combination with standard antiemetic treatment (aprepitant, palonosetron, and dexamethasone) for patients receiving highly emetogenic chemotherapy (HEC). A multi-institutional, double-blind, randomized phase II, dose-finding study of olanzapine was performed in patients with a malignant solid tumor who were receiving HEC with cisplatin (≥50mg/m2). Patients were randomly assigned either olanzapine 10 or 5mg orally on days 1-4, combined with standard antiemetic treatment. The primary endpoint was a complete response (CR; no emesis and no use of rescue medications) in the delayed phase (24-120h after the start of cisplatin treatment). 153 patients were randomized to the 10mg group (n=76) or the 5mg group (n=77). The CR rate in the delayed phase was 77.6% (80% CI: 70.3-83.8, P=0.01) in the 10mg group and 85.7% (80% CI: 79.2-90.7, P<0.001) in the 5mg group (P value for H 0: complete response rate≤65%). The most common adverse event was somnolence, which had an incidence of 53.3 and 45.5% in the 10 and 5mg olanzapine groups, respectively. Both doses of 10 and 5mg olanzapine provided a significant improvement in delayed emesis. A dose of 5mg olanzapine was determined as the recommended dose for a further phase III study based on higher CR and lower somnolence rates. UMIN000014214.