Navari, R.M., Nagy, C.K., & Gray, S.E. (2013). The use of olanzapine versus metoclopramide for the treatment of breakthrough chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic chemotherapy. Supportive Care in Cancer, 21, 1655-1663.

To compare the effectiveness of a regimen using olanzapine versus a regimen using metoclopramide for breakthrough chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy (HEC)

Patients receiving HEC were randomly assigned to receive either a regimen containing olanzapine or metoclopramide for breakthrough CINV. All patients received prophylactic antiemetics of 12 mg IV dexamethasone, 0.25 mg IV palonosetron, and 150 mg IV fosaprepitant on day 1 prior to chemotherapy. On days 2-4, patients received 4 mg oral dexamethasone, twice per day. The metoclopramide regimen was 10 mg orally every 8 hours for 72 hours. The olanzapine regimen was 10 mg daily for 72 hours. 

Those on olanzapine also received placebo once daily so that the number of pills were the same for both groups, so patients were blinded to the study group. Patients were instructed to begin the breakthrough treatment within 30 minutes after any emesis or nausea level greater than 3 on a visual analog scale (VAS). If the breakthrough treatment was begun, patients were to discontinue the oral dexamethasone, notify the on-call nurse, and begin recording nausea and any emesis. Patients were contacted by phone every 24 hours to remind them to complete information and assess toxicities.

• The study consisted of 276 patients; of these, 108 used a breakthrough regimen and were analyzed.
• Median age was 62 years with a range of 38–79.
• The study sample was 46.3% male and 53.7% female.
• Cancer diagnoses were breast, bladder, lung, and lymphoma.
• All patients were receiving HEC.

The study was conducted at multiple outpatient sites in Indiana.

All patients were in active antitumor treatment.

This was a randomized, parallel group trial.

The M.D. Anderson symptom assessment scale was used.

A total of 39% of patients randomized needed to begin the breakthrough CINV regimen as assigned.  Over the 72 hour observation period, 70% of those on olanzapine had no further emesis, compared to 31% of those on metoclopramide (p < 0.01), and 68% on olanzapine had no further nausea, compared to 23% with no nausea in the metoclopramide group (p < 0.01). The pattern of symptom control showed that the incidence of nausea and vomiting declined each study day.

A regimen of breakthrough CINV treatment using olanzapine was more effective than metoclopramide for relief of breakthrough nausea and vomiting in patients receiving HEC.

Olanzapine can be more effective than metoclopramide to manage breakthrough CINV. The breakthrough regimen tested here involved the provision of consistent medication, rather than treatment of each breakthrough episode individually, which may not be the usual approach for management. Findings here showed that about 40% of patients required a breakthrough regimen, despite use of aggressive standard antiemetic therapy. Olanzapine was found to be more effective in relieving nausea, which has been more difficult to effectively control than vomiting.  Strong consideration should be given to use of this type of olanzapine regimen and immediate patient-initiated use of such a regimen based on self assessment of CINV severity early in the course of treatment. Most current guidelines provide limited recommendations for breakthrough CINV.