Rudolph M. Navari, MD, PhD
Olanzapine, an antipsychotic medication that has been used off-label to treat patients experiencing chemotherapy-induced nausea and vomiting (CINV), has proved highly effective in controlling breakthrough CINV, according to study results released Wednesday.
The phase III trial provides the first conclusive evidence that olanzapine is beneficial for patients sapped by CINV symptoms, researchers indicated during an American Society of Clinical Oncology (ASCO) press conference. ASCO spotlighted the study in advance of its annual meeting, scheduled for June 1-5 in Chicago, Illinois, where the abstract will be presented.
“This is the first study to demonstrate an effective treatment for breakthrough CINV,” said lead investigator Rudolph M. Navari, MD, PhD, professor of medicine, associate dean and clinical director of the Harper Cancer Institute at Indiana University School of Medicine in South Bend.
CINV is among the most common and distressing adverse events associated with cancer treatment, affecting approximately 50% to 60% of patients taking certain types of chemotherapy. There are five categories of CINV; the “breakthrough” type, which affects an estimated 30% to 40% of patients, refers to nausea and vomiting that occurs after prophylactic agents have been administered.
The study involved 205 chemotherapy-naïve patients scheduled to receive highly emetogenic drugs: cisplatin for participants with advanced lung and bladder cancers, and cyclophosphamide and doxorubicin for those with breast cancer. All patients were given drugs before they started chemotherapy that were recommended guidelines.
While the drugs helped most participants, 80 patients experienced breakthrough CINV. These participants were then randomized to receive either olanzapine at a dose of 10 mg orally daily for three days or metoclopramide at a dose of 10 mg orally three times daily for three days. They were monitored for 72 hours.
During the observation period, 71% of those in the olanzapine arm (30 of 42 patients) did not experience vomiting, compared with 32% (12 of 38 patients) of those who received metoclopramide (P
< .01). In addition, 67% of patients (28/42) in the olanzapine group did not experience nausea, versus 24% (9/38) of those in the metoclopramide arm (P
The FDA has approved olanzapine for the treatment of schizophrenia and manic episodes associated with bipolar disorder. Eli Lilly and Company obtained approval for the drug in 1996 under the trade name of Zyprexa, and there are now generic versions.
Although weight gain and other adverse events have been noted in patients treated with olanzapine for psychosis, those effects occur when the drug is taken for three months to nine months, Navari said. He said olanzapine did not cause significant toxicities in the short time the patients in the CINV study took the drug.
In fact, there were no grade 3 or 4 toxicities with either olanzapine or metoclopramide, Navari said.
Metoclopramide, which the FDA first approved in the early 1980s, is indicated for the treatment of heartburn, ulcers, and sores in patients with gastroesophageal reflux disease who have not responded to standard therapies, and for symptoms of diabetes-related gastric distress. It also has been used off-label for the treatment of patients with CINV.
The positive results on olanzapine will give oncology specialists a new tool to help the significant proportion of patients who experience breakthrough CINV, commented Sandra M. Swain, MD, president-elect of ASCO, who served as a moderator at the press conference.
“We’re still reminded we need to find ways to improve the patient’s experience,” said Swain, a physician leader at the Washington Cancer Institute in the District of Columbia, noting that patients sometimes opt out of treatment because of CINV. “This is a great step forward for quality of life for our patients.”