Navari, R.M., Qin, R., Ruddy, K.J., Liu, H., Powell, S.F., Bajaj, M., . . . Loprinzi, C.L. (2016). Olanzapine for the prevention of chemotherapy-induced nausea and vomiting. New England Journal of Medicine, 375, 134–142. 

To evaluate olanzapine for chemotherapy-induced nausea and vomiting (CINV) prophylaxis in patients receiving highly emetogenic chemotherapy (HEC) and to evaluate potential toxic effects

Patients were stratified according to gender, chemotherapy regimen, and the specific 5HT3 used. All patients were on triplet antiemetic regimens. In addition, patients received 10 mg oral olanzapine daily or placebo on days 1–4. Patients were to complete daily records of vomiting, nausea severity, and use of rescue therapy.

• N = 369   
• MEDIAN AGE = 57 years
• MALES: 27.6%, FEMALES: 72.4%
• KEY DISEASE CHARACTERISTICS: Most had breast cancer, and 12% had lung cancer.
• OTHER KEY SAMPLE CHARACTERISTICS: All patients were chemotherapy-naïve, 35% were on cisplatin-based regimens, and 64% were on anthracycline and cyclophosphamide.

• SITE: Multi-site   
• SETTING TYPE: Outpatient    
• LOCATION: United States

PHASE OF CARE: Active antitumor treatment

• Double-blind, placebo-controlled, randomized controlled trial

• Visual analog scale (VAS) for nausea severity
• Complete response rated in acute and delayed phase
• Use of rescue medications

During the acute phase, 73.8% on olanzapine had no nausea compared to 45.3% on placebo (p < 0.001), and in the delayed phase, 42.4% on olanzapine and 25.4% on placebo had no nausea (p = 0.001). The complete response rate with olanzapine in the acute phase was 85.7% compared to 64.6% with placebo (p < 0.001). In the delayed phase, complete response was 66.9% with olanzapine and 53.4% with placebo (p = 0.007). Those on olanzapine had significantly more sedation on day 2, which then resolved in the following days.

The addition of olanzapine as an adjunct to standard triplet antiemetic regimens for patients receiving HEC was more effective than placebo for CINV control.

Findings suggest that the use of olanzapine as an adjunct to usual triplet therapy for CINV control was effective in improving complete response rates and nausea, although complete response rates reported here are not higher than those often reported with standard triplet therapy. Nausea was also improved with olanzapine, although almost half the participants still had nausea in the delayed phase. Clinicians can consider the addition of olanzapine to standard antiemetic regimens for individuals at high risk for CINV or those who may have had inadequate CINV control in previous chemotherapy cycles. Ongoing research is still needed to achieve greater nausea control.