In order to prevent chemotherapy-induced nausea and vomiting (CINV), 10 mg of olanzapine, an antipsychotic, is often added to standard antiemetic therapy including aprepitant, palonosetron, and dexamethasone. However, reducing the dose of olanzapine to 5 mg is recommended by guidelines to mitigate sedation, a common side effect of olanzapine. In this randomized, double-blind, placebo-controlled, phase 3 trial, researchers discovered that 5 mg of olanzapine is effective at treating CINV in patients receiving cisplatin-based chemotherapy.
For this study, results of which are published in The Lancet Oncology, 710 patients were enrolled. To be qualified for the trial, patients must have a malignant tumor (excluding those with a hematopoietic malignancy) who were scheduled to be treated with cisplatin at a dose of at least 50 mg/m2 for the first time, be between 20 and 75 years of age, and have an Eastern Cooperative Oncology Group performance status of 0-2. Participants were randomly assigned (1:1) to be administered either 5 mg of oral olanzapine or placebo once daily on days 1 to 4 combined with aprepitant, palonosetron, and dexamethasone. All patients received 50 mg/m2 of cisplatin. The proportion of patients who achieved a complete response—no vomiting or use of rescue medications in the delayed phase (24-120 hours)—was the primary end point.
Two days after initiation of cisplatin, 79% of patients in the olanzapine group achieved a complete response compared with 66% in the placebo group. One participant experienced grade 3 constipation, while another patient had grade 3 somnolence in the olanzapine group.
The study authors, led by Hironobu Hashimoto, BS, of the Department of Pharmacy of the National Cancer Center Hospital in Tokyo, Japan, concluded, "Olanzapine 5 mg combined with aprepitant, palonosetron, and dexamethasone could be a new standard antiemetic therapy for patients undergoing cisplatin-based chemotherapy."
For More Information
Hashimoto H, Abe M, Tokuyama O, et al (2019). Olanzapine 5 mg plus standard antiemetic therapy for the prevention of chemotherapy-induced nausea and vomiting (J-FORCE): a multicenter, randomized, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. [Epub ahead of print] DOI:10.1016/S1470-2045(19)30678-3
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