Published in:
01-04-2018 | Original Article
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
Authors:
Takako Yanai, Satoru Iwasa, Hironobu Hashimoto, Fumiyoshi Ohyanagi, Tomomi Takiguchi, Koji Takeda, Masahiko Nakao, Hiroshi Sakai, Toshiaki Nakayama, Koichi Minato, Takahiro Arai, Kenichi Suzuki, Yasuhiro Shimada, Kengo Nagashima, Hiroyuki Terakado, Noboru Yamamoto
Published in:
International Journal of Clinical Oncology
|
Issue 2/2018
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Abstract
Purpose
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).
Methods
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).
Results
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.
Conclusions
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
UMIN000014214