Olanzapine prevented chemotherapy-induced nausea15 Jul 2016
The antipsychotic agent olanzapine (Zyprexa, Zyprexa Zydis, Zyprexa Relprev) proved better for preventing nausea than placebo in a multicenter randomized, double-blind phase 3 trial.
Patients undergoing highly emetic chemotherapy whose prophylactic drug combination included olanzapine were more likely than those who received a placebo-containing combination to have no nausea and vomiting in the early, later, and overall assessment periods or to experience no emesis at all, reported Rudolph M. Navari, MD, PhD, of Indiana University School of Medicine-South Bend, and colleagues.
The proportion of patients with no chemotherapy-induced nausea was significantly greater with olanzapine than with standard prophylaxis plus placebo for the following three assessment periods:
- the first 24 hours after chemotherapy (74% versus 45%),
- 25 to 120 hours after chemotherapy (42% versus 25%), and
- the overall 120-hour period (37% versus 22%).
Olanzapine works by blocking multiple neurotransmitters, including dopamine and serotonin, at various receptor sites, and blocking catecholamines, acetylcholine, and histamine.
A placebo-controlled trial
The phase 3 trial randomized 380 cancer patients (mean age of 57, with 72.4% female and 90.3% of whom were white) enrolled during 2014-2015 at U.S. academic and community treatment centers. The majority of the patients (63.7%) were being treated for breast cancer, followed by lung cancer (12.9%) and other malignancies (23.4%).
Patients had not previously received chemotherapy and were receiving cisplatin (≥70 mg per square meter of body-surface area) or cyclophosphamide-doxorubicin. The study compared olanzapine with placebo in combination with dexamethasone, aprepitant or fosaprepitant, and a 5-hydroxytryptamine type 3 receptor antagonist. The number of patients receiving drug combinations, given before and after chemotherapy, were similar in both arms: 192 for olanzapine and 188 for placebo. Both groups received either 10 mg of olanzapine orally or a matching placebo daily on days 1 through 4.
No grade 5 toxic effects and no serious adverse events were observed
Nausea prevention was the primary endpoint, with a complete response of no emesis and no need for use of rescue medication the secondary endpoint. The complete-response rate was also significantly increased with olanzapine during all three periods: 86% versus 65%, 67% versus 52%, and 64% versus 41%, respectively. The authors noted that other phase 3 research has reported similar benefits with olanzapine for controlling chemotherapy-induced nausea and emesis.
Although no grade 5 toxic effects were observed, some olanzapine recipients experienced greater sedation -- rated as severe in 5% of patients -- on day 2, but this symptom generally abated on days 3, 4, and 5 despite continued administration of oral olanzapine on days 3 and 4, "suggesting that patients adapted to the drug's sedative effect," Navari and associates wrote.
There was no olanzapine-related increase in appetite, no serious adverse events, and no discontinuations due to toxic effects. "In view of the temporary drowsiness reported in this trial and previous reports, 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."
A limitation of the study is that it evaluated only a single 10-mg dose level of olanzapine, although lower or higher doses might impact efficacy, toxicity, or both. In addition, the study did not address the efficacy of olanzapine for multiple chemotherapy cycles. "These issues should be considered in future clinical trials," the researchers wrote.
Source: MedPage Today