A triple therapy of low-dose olanzapine plus granisetron and dexamethasone had durable efficacy and a reasonable safety profile for the treatment of patients with carboplatin-induced nausea and vomiting. These findings were published in The Oncologist.
Carboplatin is used to treat several types of cancer, including thoracic cancers. However, the drug is known to have a high emetic risk. Chemotherapy-induced nausea and vomiting (CINV) has a negative effect on quality of life that can lead to noncompliance and decreased treatment efficacy. The standard antiemetic prophylaxis for CINV is a 5-HT3 antagonist, dexamethasone, and a neurokinin-1 receptor antagonist (NK1 RA).
In this prospective, open-label, phase 2 trial, researchers sought to determine whether substituting olanzapine for the NK1 RA would effectively prevent CINV. Olanzapine, a multiacting, receptor-targeted agent, is highly effective as an antiemetic agent, inexpensive, and easily available. Studies have shown it to improve nausea and complete response rate in patients receiving emetogenic chemotherapy. Most studies used a 10-mg dose, which tended to have a sedative effect on patients. Therefore, this study aimed to investigate the efficacy and safety of a lower dose of olanzapine in the triple therapy.
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Fifty patients with thoracic malignancies scheduled to receive carboplatin therapy were recruited from 4 centers in Japan between February 2018 and June 2020. On day 1, patients received 1 mg intravenous granisetron and 9.9 mg intravenous or 12 mg oral dexamethasone 30 minutes prior to carboplatin. On days 2 and 3, patients received 6.6 mg intravenous or 8 mg oral dexamethasone. Patients took 5 mg oral olanzapine after dinner for 4 days. Remission status and adverse reactions were assessed.
Patients were median age 71 years (range, 34 to 79) and 70.0% were men. Malignancies represented included non-small cell lung cancer (66.0%), small cell lung cancer (22.0%), and thymoma/thymic carcinoma (10%).
Complete remission was achieved in 94.0% of patients (80% CI, 87.1%-97.8%; P <.0001) overall. Complete remission rates in the acute and delayed phases were 100% and 94.0%, respectively.
Nausea and vomiting were reported to peak on days 3 (12.0% and 4.0%, respectively) and 4 (14.0% and 4.0%, respectively). Grade 2 adverse events included constipation (32.0%), hiccups (10.0%), insomnia (6.0%), somnolence (4.0%), and dry mouth (2.0%).
In a univariate analysis, the only significant factor associated with nausea was motion sickness (odds ratio, 0.14; 95% CI, 0.022-0.841; P =.0318).
After therapy, most patients indicated they were satisfied (44.0%) or very satisfied (38.0%), with 1 indicating dissatisfaction.
Although these findings may not be generalizable to a more diverse population, study results indicated a low-dose olanzapine plus granisetron and dexamethasone triple therapy was efficacious for the treatment of carboplatin-induced CINV in patients with thoracic malignancies with a low risk for serious adverse events.
Reference
Sakai C, Shimokawa M, Iihara H, et al. Low-dose olanzapine plus granisetron and dexamethasone for carboplatin-induced nausea and vomiting in patients with thoracic malignancies: a prospective multicenter phase II trial. Oncologist. Published online April 3, 2021. doi:10.1002/onco.13772
