Related Pages Supportive Care Trial Results Provides links to clinical trial results about supportive care (care given to improve a patient's quality of life). Coping with Cancer Managing side effects and complications caused by cancer and its treatment.

Key Words
Nausea, vomiting, chemotherapy, anti-emetic drugs. (Definitions of many terms related to cancer can be found in the Cancer.gov dictionary.)

Summary
Drugs used to treat nausea and vomiting are called anti-emetics. Two studies examined a new anti-emetic drug called aprepitant (brand name EMEND®) in patients undergoing cancer treatment with the chemotherapy drug cisplatin. In both studies, patients who received aprepitant suffered less nausea and vomiting than patients who received standard anti-emetic drugs.

Source
Journal of Clinical Oncology, published online Oct. 14, 2003; in print issue Nov. 15, 2003. (See the journal abstracts for de Wit, et al., and for Hesketh, et al.)

Background
Nausea and emesis (vomiting) are common and sometimes debilitating side effects of chemotherapy. While progress has been made in reducing these side effects, it can still be hard to control symptoms that occur more than a day after chemotherapy, during repeat cycles of chemotherapy, and when chemotherapy is given on more than one day or in very high doses.

Patients receiving the anti-cancer drug cisplatin are usually evaluated for how well anti-emetics work because cisplatin makes most patients severely nauseated and because anti-emetics that work well with cisplatin tend to work well with other kinds of chemotherapy. Both studies summarized here involved patients being treated with cisplatin.

On the basis of earlier versions of these two reports, aprepitant was approved in March 2003 by the U.S. Food and Drug Administration. Aprepitant is the first of a new class of anti-emetics that work by blocking a key receptor (NK1) in the brainstem involved with vomiting and nausea.

Study 1 (Aprepitant Protocol 052 Study Group)
This phase III clinical trial involved 521 patients who were treated with cisplatin for the first time. Researchers randomly assigned patients to receive either standard anti-emetic medications only (ondansetron and dexamethasone), or standard anti-emetic medications plus aprepitant. The study was double-blinded, which means neither the patients nor their caregivers knew who was receiving which anti-emetic treatment.

Researchers evaluated the patients daily for five days after chemotherapy, and twice more later. Patients kept a diary to record all their nausea and vomiting episodes, and noted any occasions on which they had to take a different medication for their nausea (called a “rescue therapy”). On the sixth day after their chemotherapy, patients completed a survey about how nausea and vomiting had affected their quality of life during the five-day study period.

Study 1 Results (see the journal abstract)
Overall, significantly more aprepitant users (72.7 percent) experienced what the researchers called a “complete response” – that is, no vomiting and no rescue therapy – than did the group who received the standard anti-emetic medications only (52.3 percent) during the five-day study period. The results were similar during the acute phase (day one) and during the delayed phase (days two to five).

Similarly, the percentage of patients who experienced complete protection (no vomiting, no rescue therapy, and a low nausea score) was significantly better for the aprepitant group than for those who received just standard therapy.

The quality-of-life survey also showed that the new anti-emetic worked better than the standard: 74 percent of the aprepitant group reported that chemotherapy-induced nausea and vomiting had minimal or no impact on their daily life; the same was said by only 64.3 percent of those on standard therapy.

The researchers noted that “the effectiveness of aprepitant in improving the control of delayed emesis is particularly noteworthy given the modest efficacy of current treatment approaches.”

Study 2 (Rotterdam Cancer Institute, the Netherlands)
The 202 patients enrolled in this phase III double-blinded study were also first-time recipients of cisplatin. Originally, they were randomly assigned to one of three groups: Group 1 received a high dose of aprepitant in combination with standard anti-emetic medications; Group 2 received the standard medications plus a lower dose of aprepitant; and Group 3 received just the standard anti-emetic drugs. Shortly after the study began, new information prompted the researchers to discontinue the higher-dose aprepitant group. The final results of the study compared the lower-dose aprepitant group (Group 2) to the standard-only group (Group 3).

Patients were observed through a maximum of six cycles of chemotherapy. They kept a diary during this time to record episodes of nausea and vomiting. The use of rescue medication was also noted.

Study 2 Results (see the journal abstract)
Few previous studies have tested whether anti-emetics can prevent nausea and vomiting after repeated chemotherapy treatments as well as after only a single treatment. In this study, patients who received aprepitant plus standard anti-emetic medications through five or six rounds of chemotherapy experienced better control of their vomiting than did the standard-only group.

During their first cycle of chemotherapy, 64 percent of patients in the aprepitant group and 49 percent in the standard therapy group had a complete response – that is, they experienced no vomiting and required no rescue therapy.

By cycle six of the chemotherapy regimen, the percentage of patients who achieved a complete response was still high (59 percent) for the aprepitant group. In contrast, the complete response rates for patients in the standard-only group decreased to 34 percent. These differences in response (15 percentage points in the first cycle and 25 percentages points in the sixth cycle) were statistically significant. That is, they could not have occurred by chance.

Limitations
David R. Kohler, Pharm.D., of the National Institutes of Health’s Clinical Center Pharmacy Department, points out that both sets of study investigators acknowledged that aprepitant may alter the way other drugs are used by the body. “It is aprepitant’s potential for interacting with many other commonly used medicines that limits the duration for which it may be safely used and that poses a challenge for caregivers whose patients may benefit” from the relief of nausea and vomiting, he says.

In an editorial accompanying the two reports, Mark G. Kris, M.D., of the Memorial Sloan-Kettering Cancer Center and Cornell University noted that the studies do not investigate the effectiveness of aprepitant for chemotherapies that cause only a moderate level of vomiting. On the other hand, he wrote, “decades of research have proven that if an anti-emetic drug prevents cisplatin-induced emesis, it will also block emesis caused by other agents as well.”

Ted Trimble, M.D., of the National Cancer Institute’s Cancer Therapy Evaluation Program, agrees that “we still need to determine how best to use [aprepitant] in combination with other anti-emetics when giving chemotherapy that does not contain cisplatin.” Nonetheless, he said, “aprepitant appears to be another useful drug to help control nausea and vomiting” which, besides making people feel miserable, “can also discourage them from continuing their cancer treatment.”

Back to Top