Olanzapine Helps Control Chemotherapy-Related Nausea, Vomiting

Olanzapine is more effective than placebo in preventing highly emetogenic chemotherapy-induced nausea and vomiting

medwireNews: Compared with placebo, the addition of olanzapine to a triple anti-emetic regimen significantly reduces nausea and vomiting in patients using highly emetogenic chemotherapeutic agents, suggest phase III trial findings.

Olanzapine is an antipsychotic drug that inhibits multiple neurotransmitters, of which the 5-hydroxytryptamine type 3 (5-HT3) and type 2c receptors may have a role in nausea and vomiting, the study authors explain in The New England Journal of Medicine.

This double-blind trial recruited 380 individuals scheduled to receive either cisplatin at a minimum dose of 70 mg/m2 or cyclophosphamide plus doxorubicin as their first chemotherapeutic regimen. Participants were randomly assigned to receive either olanzapine 10 mg/day or placebo on days 1–4 alongside dexamethasone, a 5-HT3 receptor antagonist (palonosetron, ondansetron or granisetron) and a neurokinin-1 receptor antagonist (fosaprepitant or aprepitant).

The primary endpoint of no chemotherapy-induced nausea was achieved by significantly more patients given olanzapine compared with placebo both during the initial 24 hours post-chemotherapy and the period from 25–120 hours after chemotherapy, at 73.8% versus 45.3% and 42.4% versus 25.4%, respectively. This was also the case over the total 120-hour period, with corresponding rates of 37.3% and 21.9%.

Addition of olanzapine also led to a significant increase in the complete response rate, defined as the proportion of patients with no emesis and no use of rescue medication, in all assessment periods. During the early, later and overall periods, the complete response rates were a respective 85.7%, 66.9% and 63.6% for olanzapine-treated patients, compared with 64.6%, 52.4% and 40.6%, respectively, for those given placebo.

Undesired sedation, a known side effect of olanzapine, was significantly more common in the olanzapine versus the placebo group on day 2, with 5% of olanzapine-treated participants experiencing severe drowsiness. But the adverse event resolved on subsequent days, despite patients continuing to receive olanzapine on days 3 and 4, indicating that patients adapted to the drug’s sedative effect, say the researchers.

They add that in light of these and previous findings “more detailed information on drowsiness ratings, as well as the use of a lower dose of olanzapine (5 mg), could be explored in future trials.”

The treatment arms were comparable with respect to undesired increase in appetite, another previously reported adverse effect of olanzapine. And there were no olanzapine-related grade 3 or 4 toxicities, nor did any patient discontinue olanzapine as a result of adverse events, conclude Rudolph Navari, from Indiana University School of Medicine–South Bend in the USA, and team.

Reference

Navari RM, Qin R, Ruddy KJ, et al. Olanzapine for the prevention of chemotherapy-induced nausea and vomiting. N Engl J Med 2016; 375: 134–142. doi: 10.1056/NEJMoa1515725

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