Roxanne Nelson

May 17, 2012

May 17, 2012 —The widely used antipsychotic olanzapine (Zyprexa) can effectively control breakthrough nausea and vomiting induced by chemotherapy, according to new research.

Olanzapine has previously demonstrated efficacy in preventing chemotherapy-induced nausea and vomiting (CINV), but new data reveal that it might also be an effective rescue medicine.

The highlights of a phase 3 study were presented at a press briefing held in advance of the annual meeting of the American Society of Clinical Oncology (ASCO), which will take place next month in Chicago, Illinois.

In patients who received standard guideline-recommended prophylaxis for CINV, olanzapine was significantly better than metoclopramide in controlling breakthrough emesis and nausea, explained lead author Rudolph Navari, MD, PhD, professor of medicine at Indiana University School of Medicine in South Bend.

Metoclopramide is an antiemetic and gastroprokinetic agent commonly used to treat nausea, vomiting, and gastroesophageal reflux disease. Although it is often prescribed for breakthrough CINV, no studies have confirmed its effectiveness in this setting.

"As far as we can tell, there has not been any previous phase 3 study on the treatment of breakthrough chemotherapy nausea and vomiting," said Dr. Navari.

Superior for Both Nausea and Vomiting

The double-blind randomized trial was conducted in 80 chemotherapy-naïve patients who received highly emetogenic chemotherapy (more than 70 mg/m² of cisplatin, or more than 50 mg/m² of doxorubicin and more than 600 mg/m² of cyclophosphamide) for the treatment of bladder, breast, or lung cancer, or for lymphoma. Patients in the 2 groups were similar in age, sex, Eastern Cooperative Oncology Group (ECOG) criteria, and diagnosis.

CINV prophylaxis included dexamethasone (12 mg intravenously [IV]), palonosetron (0.25 mg IV), and fosaprepitant (150 mg IV) prior to chemotherapy, and dexamethasone (8 mg orally daily on days 2 to 4) after chemotherapy. Patients who developed breakthrough emesis of nausea despite these medications were randomized to receive oral olanzapine 10 mg daily for 3 days or oral metoclopramide 10 mg (3 times a day) for 3 days.

"The study was designed to detect a 15% difference between these 2 treatments," explained Dr. Navari. "The patients were monitored for the number of emetic episodes and the amount of nausea for 72 hours after the initiation of either treatment.

Nausea was measured on a visual analog scale (0 to 10), with 0 being no nausea and 10 being maximal nausea.

During the 72-hour observation period, 71% (n = 30) of patients in the olanzapine group had no emesis, compared with 32% (n = 12) in the metoclopramide group (P < .01). "This is a statistically significant difference," Dr. Navari emphasized.

Similarly, the number of patients without nausea was 67% (n = 28) in the olanzapine group and 24% (n = 9) in the metoclopramide group (P < .01); this difference was also statistically significant.

Both olanzapine and metoclopramide were well tolerated, and no grade 3 or 4 toxicities were noted. When taken daily for 6 months or longer for psychosis, olanzapine has been associated with a number of adverse events, but the short-term use in this study did not cause any significant adverse effects, noted Dr. Navari.

Improved Quality of Life

These are truly remarkable results.

"These are truly remarkable results," said Sandra Swain, MD, who is president-elect of ASCO. "It's a great step forward for quality of life."

About 30% of patients who undergo maximal therapy, as described in this study, will have breakthrough vomiting, despite standard preventive therapy; the number rises another 10% or 20% if nausea is added to the equation, she said. "That is a significant proportion of patients."

"In this era of precision medicine, where we can really focus in on cancers and treat them effectively, we are reminded that we need to find ways to improve the patients' experiences," she explained. "These effects can be intolerable; sometimes patients will opt out of curative treatment, and we certainly don't want that."

The authors have disclosed no relevant financial relationships.

2012 Annual Meeting of the American Society of Clinical Oncology. Abstract 9064. To be presented June 2, 2012. Abstract


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