Abe, M., Hirashima, Y., Kasamatsu, Y., Kado, N., Komeda, S., Kuji, S., . . . Ito, K. (2015). Efficacy and safety of olanzapine combined with aprepitant, palonosetron, and dexamethasone for preventing nausea and vomiting induced by cisplatin-based chemotherapy in gynecological cancer: KCOG-G1301 phase II trial. Supportive Care in Cancer, 24, 675–682. 

To investigate the effects of olanzapine as an adjunct to triplet antiemetic therapy for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy

All patients in the trial were receiving triplet therapy in accordance with Japanese guidelines and 5 mg olanzapine one day prior to cisplatin administration then once daily on days 1–5 at bedtime. Metoclopramide was used as rescue therapy for breakthrough emesis. Patients were hospitalized during treatment.

• N = 40
• MEDIAN AGE = 57 years (range 25–76 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: All had cervical, endometrial, or vulval cancer at varied stages. 50% experienced emesis during pregnancy, and 32.5% had a history of motion sickness. Most received cisplatin at a dose of 50mg/m² and 95% had multiagent regimens.

• SITE: Multi-site  
• SETTING TYPE: Inpatient    
• LOCATION: Japan

• PHASE OF CARE: Active antitumor treatment

Prospective trial

• Patient diary for daily self-reported symptoms
• Eleven-point Numeric Rating Scale (NRS) for nausea
• Complete response defined as no vomiting, no rescue therapy and no significant nausea
• Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

There were no grade 3 or 4 adverse events. In the overall phase (acute and delayed phases), the complete response rate was 92.5% with 97.5% in the acute phase and 95% in the delayed phase. The rate for no nausea was 87.5% in the acute phase and 67.5% in the delayed phase. The authors provided a comparison of this study's results with those of a collaborative group trial using triplet therapy. This comparison showed that the addition of olanzapine was associated with better response rates across all phases and higher rates of nausea control. The adverse effects reported were low-grade and included constipation, dry mouth, and dizziness.

The addition of olanzapine to triplet antiemetic therapy in patients receiving highly emetogenic chemotherapy was associated with high rates of complete CINV control across all phases and relatively low rates of nausea during the acute phase.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Other limitations/explanation: The results were complete control and no significant nausea, but these were not defined and the level of no significant nausea was not clear. The way in which the numeric scale data were used was not clear (i.e., was this the average, worst, or least scores recorded by the patient).

Triplet drug therapy to prevent CINV is recommended and is effective with highly emetogenic chemotherapy. However, even with this approach, the control and prevention of nausea is challenging. The findings of this study suggest the addition of olanzapine to triplet therapy may improve nausea control and overall CINV prevention with no severe adverse effects. This study has several limitations, but provides promising results. Additional, well-designed research testing the impact of olanzapine for CINV prevention is warranted.