New drug reduces chemotherapy-induced nausea and vomiting

Two new studies now show that aprepitant – the first in a new class of drugs that interfere with the vomiting reflex – can substantially reduce chemotherapy-associated nausea and vomiting in cancer patients treated with cisplatin, a common type of chemotherapy. Results of both Journal of Clinical Oncology studies, early release articles published online October 14, formed the basis of the U.S. Food and Drug Administration’s approval of aprepitant in March 2003.

Aprepitant Combined with Standard Treatment for Nausea and Vomiting Helps Prevent These Symptoms Following Chemotherapy

The first study, led by Paul J. Hesketh, MD, at the Caritas St. Elizabeth’s Medical Center in Boston, found that adding aprepitant to the standard therapy to control nausea and vomiting could more effectively prevent these symptoms than the standard treatment alone. Nausea and vomiting were reduced both on the day that chemotherapy was given and, more importantly, in the several days that followed, when nausea and vomiting often occur.

“The nausea and vomiting that occurs 24 hours after receiving cisplatin is particularly problematic for patients, and aprepitant provided a substantial improvement,” said Dr. Hesketh. “Aprepitant should change the standard of care for the treatment of chemotherapy-induced nausea and vomiting, especially for patients receiving chemotherapy drugs known to cause severe vomiting.”

The international phase III study involved 520 patients with respiratory cancers, all of whom received ondansetron plus dexamethasone – the standard therapy to prevent nausea and vomiting. In addition, the patients were randomly assigned to receive oral aprepitant or a placebo. Patients kept diaries to document any nausea or vomiting that occurred on the day that chemotherapy was given and on the four days that followed, noting whether they needed additional medication to control these symptoms.

Researchers found that 26 percent of patients on the aprepitant regimen experienced nausea or vomiting, while nearly 48 percent of patients on the standard treatment experienced these side effects.

Results were particularly encouraging two to five days after the administration of chemotherapy, when standard treatments often fail. During this time period, 25 percent of patients on the aprepitant regimen reported nausea or vomiting, compared to 44 percent of those taking the standard drugs.

Aprepitant Added to Standard Therapy Protects Against Nausea and Vomiting Over Multiple Cycles of Chemotherapy

The second study, led by Ronald de Wit, MD, PhD, of the Rotterdam Cancer Institute in the Netherlands, found that the benefits of aprepitant extended over the course of multiple cycles of chemotherapy. Previous studies have shown that nausea and vomiting often become more severe over the course of several cycles of chemotherapy, and that standard therapy to control nausea and vomiting tends to become less effective as the number of chemotherapy cycles increases.

“This is a major clinical improvement in the ability to control nausea and vomiting – two of the most distressing side effects of chemotherapy,” said Dr. de Wit. “The benefits experienced by patients taking aprepitant should be considered a major leap forward.”

The international phase II clinical trial involved 164 cancer patients, all of whom were scheduled to receive up to six cycles of cisplatin. Recruited from 50 centers, including 21 in the United States, patients were randomly assigned to receive either oral aprepitant or a placebo, in addition to ondansetron and dexamethasone. Patients kept diaries identical to those in the previous study.

Researchers found that 64 percent of patients taking aprepitant plus standard therapy experienced no nausea or vomiting after the first cycle of cisplatin, compared to 49 percent of patients taking only the standard therapy. After six cycles of cisplatin therapy, 59 percent of patients who continued to take aprepitant along with the standard therapy reported no nausea or vomiting, compared to only 34 percent of those who received the standard therapy alone.

“This study shows that the benefits of aprepitant are not confined to the first cycle of chemotherapy and that this enhanced protection against nausea and vomiting can be sustained,” said Dr. de Wit.

“The Oral NK1 Antagonist Aprepitant For the Prevention of Chemotherapy Induced Nausea and Vomiting: A Multinational, Randomized, Double-Blind, Placebo Controlled Trial in Patients
Receiving High-Dose Cisplatin.” Paul J. Hesketh, M.D., et al; Caritas St. Elizabeth’s Medical Center, Boston, Massachusetts.

“Addition of the Oral NK1 Antagonist Aprepitant (EMEND®) To Standard Antiemetics Provided Protection Against Nausea and Vomiting during Multiple Cycles of Cisplatin-Based Chemotherapy.”
Ronald de Wit, M.D., et al; Rotterdam Cancer Institute, Rotterdam, The Netherlands.

The Journal of Clinical Oncology is the semi-monthly peer-reviewed journal of the American Society of Clinical Oncology (ASCO), the world’s leading professional society representing physicians who treat people with cancer.