There are good drugs that can prevent nausea in patients undergoing chemotherapy, but unfortunately antiemetics do not work for all patients. The atypical neuroleptic drug olanzapine, which is normally used for schizophrenia and manic phases, has now been tested for its antiemetic effect in a clinical trial.
Nausea and vomiting are common side effects of chemotherapy, and many patients are also particularly afraid of feeling sick all the time during chemotherapy. Accordingly, there are also patients who discontinue chemotherapy because of nausea if the usual antiemetics do not work for them or work only insufficiently.
Atypical neuroleptic for nausea?
A randomized, double-blind, multicenter phase 3 trial has now investigated whether the additional administration of olanzapine can prevent nausea and vomiting during chemotherapy [1]. Olanzapine is an atypical neuroleptic. So far, it has been used to treat schizophrenia and manic phases in bipolar disorders. It regulates dopamine and serotonin receptors, which are also involved in the pathogenesis of nausea and vomiting. The study was co-funded by the U.S. National Cancer Institute.
380 patients who had never received chemotherapy before participated in the study. All were scheduled to receive chemotherapy with a high risk of nausea and vomiting (cisplatin or cyclophosphamide-doxorubicin). Patients were treated with a combination of an NK1 receptor antagonist, 5-HT3 antagonist, and dexamethasone to prevent nausea; half of the patients also received olanzapine (10 mg/d p.o. for the first four days of the chemotherapy cycle), and the other half received placebo.
Significantly less nausea and vomiting
In the verum group, the number of patients spared from nausea (primary endpoint) was significantly greater than in patients receiving standard therapy alone: 74% in the first 24 hours after the start of chemotherapy (vs. 45% in the group without olanzapine), 42% in the period 25-120 hours after chemotherapy (vs. 25%), and 37% in the entire study period of 120 hours (vs. 22%). Also the secondary endpoint, no vomiting resp. no use of rescue medication, significantly more patients in the verum group achieved: in the first 24 hours, 86% (vs. 65%); in the 25-120 hour period, 67% (vs. 52%); and in the entire period, 64% (vs. 41%). No grade 5 toxicities occurred; however, in the olanzapine therapy group, some patients experienced increased sedation on the second day of chemotherapy (severe sedation in 5%).
The authors concluded that olanzapine was a valuable adjunct to antiemetic therapy and could spare cancer patients nausea and vomiting during chemotherapy.
Literature:
- Navari RM, et al: Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting. N Engl J Med 2016; 375: 134-142.
InFo ONCOLOGY & HEMATOLOGY 2016; 4(5): 5
