A double-blind randomized phase II dose-finding study of olanzapine 10 mg or 5 mg for the prophylaxis of emesis induced by highly emetogenic cisplatin-based chemotherapy
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The aim of this phase II study was to evaluate the efficacy and safety of two doses (10 and 5 mg) 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 (≥ 50 mg/m2). Patients were randomly assigned either olanzapine 10 or 5 mg 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 (24–120 h after the start of cisplatin treatment).
153 patients were randomized to the 10 mg group (n = 76) or the 5 mg group (n = 77). The CR rate in the delayed phase was 77.6% (80% CI: 70.3–83.8, P = 0.01) in the 10 mg group and 85.7% (80% CI: 79.2–90.7, P < 0.001) in the 5 mg 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 5 mg olanzapine groups, respectively.
Both doses of 10 and 5 mg olanzapine provided a significant improvement in delayed emesis. A dose of 5 mg olanzapine was determined as the recommended dose for a further phase III study based on higher CR and lower somnolence rates.
Clinical Trial Information
KeywordsOlanzapine Chemotherapy-induced nausea and vomiting Prophylaxis Phase II study
The authors thank the patients, clinical investigators, and site personnel who participated in the study. Additional participating institutions and investigators included Shikoku Cancer Center (Daijiro Harada, Yuki Kogure). This work was supported in part by the Foundation for Promotion of Cancer Research in Japan.
Compliance with ethical standards
Conflict of interest
Satoru Iwasa, Koji Takeda, Yasuhiro Shimada and Noboru Yamamoto have received payment for lectures and research funding from Eli Lilly. All remaining authors have declared no conflicts of interest.
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