Low-dose olanzapine combined with aprepitant, palonosetron, and dexamethasone may be highly effective at preventing chemotherapy-induced nausea and vomiting in patients undergoing cisplatin-based chemotherapy, according to phase 3 study results published in The Lancet Oncology,
Guidelines from the American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network (NCCN) recommend an olanzapine dose of 10 mg for the prevention of chemotherapy-induced nausea and vomiting, but it may be possible to reduce the dose of olanzapine to 5 mg for patients older than 75 years and those who suffer from excessive sedation while receiving olanzapine.
Previous phase 2 studies have suggested that a 5 mg dose of olanzapine may have equivalent activity to a 10 mg dose, as well as a favorable safety profile in relation to somnolence. To assess this, researchers in Japan conducted a randomized, double-blind, placebo-controlled, phase 3 study at 26 hospitals.
A total of 710 patients with a malignant tumor who were scheduled for treatment with cisplatin were assigned to receive either 5 mg olanzapine (356 patients) or placebo (354 patients) along with palonosetron, aprepitant, and dexamethasone. All patients were between 20 and 75 years old and had an Eastern Cooperative Oncology Group (ECOG) performance status between 0 and 2. Patients reported the frequency and severity of any nausea and vomiting they experienced.
The primary end point was the proportion of patients who achieved complete response during the delayed phase (24 to 120 hours after initiation of highly emetogenic chemotherapy). Other outcomes included the proportion of patients who achieved complete control, defined as reporting no more than mild nausea, and the proportion of patients who achieved total control, defined as reporting no nausea.
In the delayed phase, 280 patients (79%) in the olanzapine group achieved a complete response compared with 231 patients (66%) in the placebo group (P <.0001). Olanzapine was found to sufficiently control chemotherapy-induced nausea and vomiting, with more patients in the olanzapine group achieving both complete control (76% vs 61%; P <.0001) and total control (59% vs 48%; P <.0049) compared with the placebo group.
“Our findings showed that [5 mg olanzapine] combined with aprepitant, palonosetron, and dexamethasone could be a new standard antiemetic therapy in patients undergoing cisplatin-based chemotherapy,” wrote the researchers.
- Hashimoto H, Abe M, Tokuyama O, et al. Olanzapine 5 mg plus standard antiemetic therapy for the prevention of chemotherapy-induced nausea and vomiting (J-FORCE): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 200;21:242-249.