About the Discussion

@NEJM Ask the Authors & Experts: The Prevention of Chemotherapy-Induced Nausea and Vomiting with Olanzapine

Original Article

Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting

Rudolph M. Navari, M.D., Rui Qin, Ph.D., Kathryn J. Ruddy, M.D., Heshan Liu, Ph.D., Steven F. Powell, M.D., Madhuri Bajaj, M.D., Leah Dietrich, M.D., David Biggs, M.D., Jacqueline M. Lafky, M.S., and Charles L. Loprinzi, M.D.


N Engl J Med 2016;375:134-42. DOI: 10.1056/NEJMoa1515725

BACKGROUND
We examined the efficacy of olanzapine for the prevention of nausea and vomiting in patients receiving highly emetogenic chemotherapy.

METHODS
In a randomized, double-blind, phase 3 trial, we compared olanzapine with placebo, in combination with dexamethasone, aprepitant or fosaprepitant, and a 5-hydroxytryptamine type 3–receptor antagonist, in patients with no previous chemotherapy who were receiving cisplatin (≥70 mg per square meter of body-surface area) or cyclophosphamide–doxorubicin. The doses of the three concomitant drugs administered before and after chemotherapy were similar in the two groups. The two groups received either 10 mg of olanzapine orally or matching placebo daily on days 1 through 4. Nausea prevention was the primary end point; a complete response (no emesis and no use of rescue medication) was a secondary end point. 

RESULTS
In the analysis, we included 380 patients who could be evaluated (192 assigned to olanzapine, and 188 to placebo). The proportion of patients with no chemotherapyinduced nausea was significantly greater with olanzapine than with placebo in the first 24 hours after chemotherapy (74% vs. 45%, P=0.002), the period from 25 to 120 hours after chemotherapy (42% vs. 25%, P=0.002), and the overall 120-hour period (37% vs. 22%, P=0.002). The complete-response rate was also significantly increased with olanzapine during the three periods: 86% versus 65% (P<0.001), 67% versus 52% (P=0.007), and 64% versus 41% (P<0.001), respectively. Although there were no grade 5 toxic effects, some patients receiving olanzapine had increased sedation (severe in 5%) on day 2.

CONCLUSIONS
Olanzapine, as compared with placebo, significantly improved nausea prevention, as well as the complete-response rate, among previously untreated patients who were receiving highly emetogenic chemotherapy. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02116530.)

 Originally Appeared in The New England Journal of Medicine on July 14, 2016.

Click here to read the original article.