"Current guidelines for the management of nausea and vomiting in patients with advanced cancer have not specifically indicated that one drug looks substantially better than a variety of other drugs. However, we believe the present results may be viewed as a best practice for treating nausea and vomiting in patients with advanced cancer-associated nausea and vomiting."
Olanzapine administered once daily at 5 mg may be effective for controlling nausea and vomiting unrelated to chemotherapy, as well as improving quality of life, in patients with advanced cancer, announced Mayo Clinic. This is the first drug studied in this setting that demonstrated a decrease in nausea and vomiting.1
The decreases in nausea and vomiting observed with olanzapine were statistically significant, according findings from an interventional study published in JAMA Oncology.
The change in the median nausea score from baseline to day 7, indicated on a scale of 0 to 10 with 10 being the worst, was improved in the olanzapine arm compared with placebo (95% CI, -8 to -7; P =.001). The median number of vomiting episodes among patients on the study was also reduced from baseline to day 7 in the experimental arm from 2 to 0 compared with 3 to 2 in the control arm (95% CI, -2 – 1; P =.001).2
"Current guidelines for the management of nausea and vomiting in patients with advanced cancer have not specifically indicated that one drug looks substantially better than a variety of other drugs," said Charles Loprinzi, MD, a medical oncologist, Mayo Clinic, in a press release.1 "However, we believe the present results may be viewed as a best practice for treating nausea and vomiting in patients with advanced cancer-associated nausea and vomiting."
Approximately 30 patients were enrolled and randomized 1:1 to receive olanzapine or placebo for 7 days. All patients were evaluable for the primary end point. All 15 participants in the olanzapine arm completed treatment, but 1 patient in the placebo arm did not. The median age of patients was 63 years (range, 39-79), and the ratio of women versus men was almost equal, including 16 women and 14 men. The median nausea score was 9 out of 10 (range, 8-10) at baseline.2
Baseline evaluations included an assessment of symptoms for the intensity of appetite, nausea, fatigue, sedation, and pain, which were measured by a numeric rating. Patients circled 1 number from 0 to 10 that best described the way they felt in the preceding 24 hours. Investigators also had patients record the number of vomiting episodes that had occurred within the 24 hours. Patient well-being was also recorded on a 0 to 10 numeric rating score, with 0 being the worst possible and 10 being the best possible.
Patients reported the intensity of these AEs every day for 7 days, as well as their overall well-being and the number of vomiting events. The objective was to measure the effect of the drug compared with placebo on chronic nausea and vomiting. The primary end point was the change in nausea scores from baseline to the last day on treatment. Numeric rating scores were summarized for nausea, appetite, fatigue, sedation, pain, and well-being, as well as emesis events, separately by median and range by treatment arm.
After 1 day of treatment, the median nausea score in the experimental arm was 2 out of 10 (range, 2-3) compared with 9 out of 10 in the placebo arm (range, 8-10), and after 1 week, the median nausea scores were 1 out of 10 (range, 0-3) and 9 out of 10 (range, 8-10), respectively. A reduction of 8 points was observed in the nausea scores in the olanzapine arm (95% CI, 7-8) compared with the placebo arm.
In the olanzapine arm, patients reported less emesis or vomiting events, less use of other antiemetic agents, a better appetite, less sedation, less fatigue, and better well-being compared with patients in the placebo arm.
In regard to the patient well-being scores, whereas 10 was the highest improved quality of life, the olanzapine arm had a score of 2 (range, 2-8) at baseline and 7 (range, 6-8) at day 7 compared with 2 (range, 2-7) and 2 (range, 2-3) in the placebo arm, respectively.
One patient in the placebo arm stopped treatment early on day 5 due to a lack of perceived benefit. Investigators noted that no patients who receive olanzapine had excess sedation or any other adverse event (AE).
Following the end of this study, patients on olanzapine were allowed to continue receiving therapy as a prescription medication from their physician. Months after the study was completed, physicians were contacted for follow-up regarding the patients who remained on therapy, revealing that all patients continued treatment daily at the 5 mg dose with continued efficacy and no toxic effects attributed to the study drug.
All patients who had received placebo were also offered olanzapine, and 13 if the 14 patients continued on this treatment once daily at 5 mg. These patients reported marked efficacy and few or no toxic effects from olanzapine.
The drug was continued for 3 to 12 weeks, and the reasons for discontinuation in both arms of the study were disease progression, inability to take oral medications, or death.
To be included in this study, adult patients had to have a malignant disease in an advanced and incurable stage, and they could not have received prior chemotherapy or radiotherapy 14 days prior to study or antipsychotic medications within 30 days. All eligible patients had chronic nausea that had been observed for at least 1 week.
"It's well-appreciated by most people that patients receiving cancer chemotherapy suffer from nausea and vomiting," stated Loprinzi.1 "However, it's less well-appreciated that patients with advanced cancer also have significant problems with nausea and vomiting that are unrelated to chemotherapy."
Overall, the agent substantially reduced nausea and vomiting among patients with advanced cancer and appeared to be generally well-tolerated.2