Olanzapine Helps Prevent Nausea and Vomiting Caused by Chemotherapy
, by NCI Staff
A drug currently used to treat several psychiatric conditions can help prevent nausea and vomiting in patients receiving chemotherapy, according to results from a large NCI-funded phase III clinical trial.
Patients in the trial were being treated with chemotherapy agents that often cause substantial nausea and vomiting. Those who were randomly assigned to receive the drug olanzapine (Zyprexa®), given in combination with three standard antiemetic agents (drugs that help prevent nausea and vomiting), were far less likely to experience nausea, have vomiting episodes, or need “rescue” anti-nausea medications to treat nausea/vomiting than patients who received a placebo plus the three antiemetic drugs.
The investigators believe the findings from this large trial, published July 14 in the New England Journal of Medicine, will likely cement the drug’s role as an important new option for managing this common and often debilitating side effect.
“In my mind, it further establishes a new standard of care,” said the study’s senior author, Charles Loprinzi, M.D., of the Mayo Clinic Cancer Center.
Looking to Confirm Earlier Evidence
Broadly accepted treatment guidelines recommend prescribing a combination of antiemetic agents for patients who are being treated with chemotherapy drugs that are likely to induce nausea and vomiting, including cisplatin, doxorubicin, and cyclophosphamide.
The antiemetic drugs—all of which act on components of the central nervous system—include dexamethasone (a type of steroid) and agents from two classes of therapies known as 5-HT3 receptor antagonists and NK-1 receptor antagonists.
These therapies may be only partially effective in some patients, and researchers have continued to search for additional options to prevent or control nausea and vomiting, which can not only harm patients’ quality of life but also disrupt treatment, potentially hindering its efficacy.
Olanzapine, which is approved by the Food and Drug Administration for the treatment of schizophrenia and bipolar disorder, targets receptors in the brain that have been linked to nausea and vomiting. Earlier trials showed that olanzapine could improve the efficacy of existing antiemetic treatments, enough so that the National Comprehensive Cancer Network had already recommended it as an option for patients being treated with chemotherapy agents with a moderate to severe risk of inducing nausea and vomiting.
But a larger trial was needed to confirm the efficacy and safety of adding olanzapine to existing therapies, the trial’s lead investigator Rudolph Navari, Ph.D., M.D., and his colleagues wrote.
More than 400 patients were enrolled in the randomized trial. The majority of the participants were women, and the most common cancer type among participants was breast cancer, with lung cancer a distant second. The patients, all of whom were being treated with cisplatin or with cyclophosphamide and doxorubicin, were randomly assigned to receive olanzapine or a placebo, in combination with the other three drugs, immediately before and for 3 more days after receiving their first dose of chemotherapy.
Patients who received olanzapine were far less likely to experience nausea in the first 24 hours after their chemotherapy treatment (75% reported no nausea, versus 45% in the placebo arm), 1 to 5 days after treatment (42% versus 25%), and during the entire 5-day period (37% versus 22%).
Patients treated with olanzapine were also much less likely to experience vomiting or to receive rescue medication to control vomiting during the time periods measured.
Adding olanzapine to the other three agents also appeared to be generally safe. Some patients who received the drug did experience excessive tiredness, or sedation, with approximately 5% reporting severe sedation. This effect generally occurred on the second day of treatment, Dr. Loprinzi said. But it largely resolved in the ensuing days, even though patients continued to receive the drug.
“We didn’t see any substantial drowsiness in the last day or two of treatment,” he said.
“The findings are certainly compelling,” said Ann O’Mara, Ph.D., R.N., head of Palliative Care Research in NCI’s Division of Cancer Prevention.
Although the use of olanzapine means adding another drug to the treatment regimen, Dr. O’Mara said she didn’t feel most patients or clinicians would consider that an impediment to its use. Patients will only be taking olanzapine and the other antiemetic agents for 4 days at a time, she noted.
“And given that nausea and vomiting remain one of the most feared side effects of chemotherapy, I think most patients will be motivated to adhere to this short-term intervention,” she said.
The trial only tested use of olanzapine for the first cycle of chemotherapy. Ideally it would be best to have trial data for its use in additional cycles, Dr. Loprinzi noted. Nevertheless, he continued, “there are no indications that it shouldn’t work for subsequent chemotherapy cycles.”