Olanzapine versus Metoclopramide for Treatment of Nausea and Vomiting in Advanced Cancer Patients with Incomplete Malignant Bowel Obstruction

Dear Editor:

Incomplete malignant bowel obstruction (iMBO) is a leading cause of nausea and vomiting in patients with advanced cancer, but empirical evidence of effective pharmacological management is extremely limited.^1,2 In general, metoclopramide is administered to patients with nausea owing to iMBO. We planned a randomized clinical trial to compare the antiemetic activity of olanzapine and metoclopramide in advanced cancer patients who had iMBO. However, we discontinued this trial because of slow recruitment, likely attributable to the severe condition of the studied population; most enrolled patients died within 30 days. Finally, 16 patients were randomized to receive either olanzapine or metoclopramide and completed the study treatment. The study was small and lacked power but is promising for stimulating further research and discussion on the topic.

Enrolled patients had advanced cancer, with an average nausea score of >4/10 owing to iMBO. They were randomized to receive olanzapine 5 mg/day or metoclopramide 20–30 mg/day for 3 days. We evaluated changes in the mean scores on a numerical rating scale (NRS) for 3 days, rate of 30% reduction in NRS score, number of vomiting episodes, satisfaction rating of patients, and preference to continue with the treatment. The frequency of severe toxicities and adverse events was also recorded by the treating physicians, as needed. The study was approved by the ethics committees affiliated to each facility, and written informed consent was obtained from all participants. The study was performed according to the Helsinki Declaration. The trial was registered at UMIN-CTR (UMIN 000010317).

Changes in nausea score for 3 days were −3.17 and −2.38 in the olanzapine and metoclopramide groups, respectively, without statistical difference (95% confidence interval: −2.71 to 1.13; p = 0.39). The rate of 30% reduction in NRS score was 87.5% versus 50% (p = 0.11). The average number of daily vomiting episodes in the olanzapine and metoclopramide groups for 3 days decreased from 3.00 to 0.75 and from 1.50 to 0.65 (p = 0.83); patient satisfaction rate was 87.5% and 75%, and preference was 100% and 50%, respectively (Table 1). Olanzapine and metoclopramide induced adverse events such as drowsiness and dizziness. However, most symptoms were of low grade, and no patient chose to stop the antiemetic treatment for these reasons.

Our study had certain limitations, including the lack of blinding and uncertainty about testing equieffective doses. Although our results are not conclusive, changes in nausea score, percentage of patients (85%) with a 30% decrease (p = 0.11), satisfaction, and preference were higher in the olanzapine group than in the metoclopramide group. These results suggest the potential epiefficacy of olanzapine and metoclopramide against nausea and vomiting in patients with advanced cancer who have iMBO.