Anti-Nausea Benefit Observed With Olanzapine in Patients Receiving HEC Regimen

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For patients receiving highly emetogenic chemotherapy, olanzapine (Zyprexa) was found to demonstrate a significant improvement in the prevention of nausea when it was added to a standard antiemetic regimen.

Steve Powell, MD

For patients receiving highly emetogenic chemotherapy (HEC), olanzapine (Zyprexa) was found to demonstrate a significant improvement in the prevention of nausea when the FDA-approved antipsychotic agent was added to a standard antiemetic regimen.

Olanzapine blocks multiple neurotransmitters, some of which may be involved in nausea and vomiting. This suggests that it might have clinically significant properties for the prevention of chemotherapy-induced nausea and vomiting (CINV). Known side effects of the agent with short-term use in its approved setting include mild sedation.

“We’ve long known the nausea and vomiting that come along with chemotherapy are a major problem and affect the quality of life of our patients,” said study author Steven Powell, MD, an oncologist at Sanford Health in Sioux Falls, South Dakota, and a community co-chair of the study, in a statement. “The findings of this study, fortunately, provide physicians with a tool to better address the needs of those they are treating for cancer.”

The phase III trial enrolled 380 chemotherapy-naïve patients being treated with HEC (either cisplatin or cyclophosphamide-doxorubicin). They were randomized to 2 groups, with 190 patients given 10 mg of olanzapine orally and 188 a matching placebo on days 1 through 4 of chemotherapy. All patients in both cohorts were treated with an antiemetic regimen of dexamethasone, aprepitant or fosaprepitant, and a 5-HT3—receptor antagonist, as well.

The study’s primary endpoint of no nausea was assessed during 3 time periods: early assessment (0-24 hours), later assessment (25-120 hours), and overall (0-120 hours) after chemotherapy. Researchers were also interested in comparing complete response (no emesis and no use of rescue medication) in the 2 study arms over the 3 phases, as well as any toxicities related to olanzapine.

Patients were asked to record any daily episodes of vomiting or retching, the use of rescue therapy, and daily levels of nausea from the first day of chemotherapy through day 5. A study nurse also contacted each patient on days 2 through 5 to ask about and record any side effects related to the regimen.


In the olanzapine arm, 73.8% of patients experienced no nausea during the early assessment period versus 45.3% of patients with placebo (P = .002). During later assessment, nausea was prevented in 42.4% of patients with olanzapine, versus 25.4% in the control arm (P = .002), and during the overall period, no nausea was reported in 37.3% of patients receiving olanzapine compared with 21.9% with placebo (P = .002).

The complete response rate also was better with olanzapine compared with placebo during the acute phase (85.7% vs 64.6%, respectively; P <.001), the delayed phase (66.9% vs 52.4%; P = .007), and over the entire period (63.6% vs 40.6%; P <.001).

In keeping with olanzapine’s known side effect profile, drowsiness was significantly increased on day 2 in the experimental arm and was severe in 5% of patients, the researchers reported; however, no patients stopped taking olanzapine as a result, and the study showed that sedation resolved after the first day, even though patients in the olanzapine arm were still taking the drug on days 3 and 4.

The researchers suggested that lower dosing of olanzapine (eg, 5 mg) represents an area for further study, adding that evaluating the agent only at the 10-mg dose is one limitation of this trial. In addition, they reported no significant differences between the 2 arms on the side effect of undesired increase in appetite on days 2 through 5 after chemotherapy.

Three grade 4 adverse events (AEs)—including 2 hematologic—were seen in the olanzapine arm and none in the placebo arm. Two grade 3 AEs occurred in the experimental arm—hyperglycemia and fatigue; in the placebo arm, 2 grade 3 AEs (diarrhea and abdominal pain) were observed. Notably, however, treating clinicians did not attribute any of the grade 3/4 AEs to the study drug.

Study authors explained that although previous research has shown that NK-1 receptor antagonists (aprepitant, fosaprepitant, netupitant, and rolapitant) provide significant control of early and later emesis in patients receiving HEC, “they appear to have been less effective in controlling nausea”—an unmet need. Based on the findings of this trial, they wrote, “Patients who received olanzapine were more likely than those who received placebo to be free of nausea and emesis in the early, later, and overall assessment periods.”


Navari RM, Qin R, Ruddy KJ, et al. Olanzapine for the prevention of chemotherapy-induced nausea and vomiting. N Engl J Med. 2016;375(2):134-142.