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Olanzapine prevents nausea in patients treated with emetogenic chemotherapy
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Olanzapine significantly improved nausea prevention among previously untreated patients receiving highly emetogenic chemotherapy, according to the results of a double blind phase 3 trial published in The New England Journal of Medicine.
Further, olanzapine improved the rate of complete response, defined as no emetic episodes and no use of rescue medication.
Rudolph M. Navari
“Previous studies used complete response as an endpoint and showed that current drugs control emesis reasonably well but not nausea,” Rudolph M. Navari, MD, PhD, FACP, director of the World Health Organization Cancer Care Program for Central and South America, told HemOnc Today. “We chose the primary endpoint, ‘no nausea’ in order to see if olanzapine worked as an antinausea medication.”
A previous phase 3 study showed that olanzapine combined with standard antiemetic agents — or single doses of dexamethasone and palonosetron — effectively controlled early and longer-term nausea and vomiting in patients who received moderate or highly emetogenic chemotherapy.
However, a recent review of these data raised questions regarding the methodology of the single-institution nature of the study.
Navari and colleagues evaluated olanzapine compared with placebo for nausea control in 380 patients (72.4% women; median age, 57 years; range, 28-89) who were receiving highly emetogenic chemotherapy in a randomized, multicenter phase 3 trial. The most common cancer sites were breast (63.7%) and lung (12.9%).
All patients received a 5-hydroxytryptamine type 3 receptor antagonist, dexamethasone and a neurokinin-1 receptor antagonist.
Researchers randomly assigned patients to receive an oral placebo (control, n = 188) or olanzapine (n = 192; 10 mg days 1-4).
A score of 0 on the visual-analogue scale indicated no nausea and served as the primary endpoint. Researchers focused on nausea prevention at three assessment periods: overall (0-120 hours), early (0-24 hours) and late (25-120 hours).
Researchers used patient records to evaluate the secondary endpoint of complete response, or no emetic episodes and no use of rescue medication.
A greater proportion of patients in the olanzapine group than the control group had a nausea score of 0 overall (37% vs. 22%) during the early period (74% vs. 45%) and the late period (42% vs 25%; P = .002 for all).
Further, a higher proportion of patients assigned olanzapine achieved complete response at all assessment periods (overall, 85.7% vs. 64.4%; P < .001; early, 63.6% vs. 40.6%; P = .007; later, 66.9% vs. 52.4%; P < .001).
Two patients in each group experienced grade 3 adverse events, (olanzapine, fatigue and hyperglycemia; control, abdominal pain and diarrhea). Three patients in the olanzapine group experienced grade 4 adverse events compared with no patients in the control arm. No patient experienced a grade 5 event.
More patients in the olanzapine group experienced significantly increased sedation on day 2 compared with baseline. Sedation appeared to resolve on days 3 through 5, even as patients continued to receive olanzapine.
“About 20% of patients experienced sedation on day 2 of olanzapine. However, no participant stopped receiving olanzapine as a result of sedation,” Navari told HemOnc Today.
Researchers acknowledged that evaluating only one dose of olanzapine, and not evaluating olanzapine over multiple cycles of chemotherapy, may have limited findings.
“Olanzapine has a fixed half-life over 4 days and chemotherapy cycles are typically multiple weeks apart,” Navari said. “I do not see any reason why olanzapine wouldn’t be effective for multiple cycles of chemotherapy.” – by Nick Andrews
For more information:
Rudolph M. Navari , MD, can be reached at rmnavari@gmail.com.
Disclos ure: Navari reports no relevant financial disclosures. Please see the study for a full list of all other researchers’ relevant disclosures.
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