FDA approves aprepitant for chemotherapy-induced nausea and vomiting

Sixty-four percent of patients receiving aprepitant with ondansetron and dexamethasone reported minimal or no effect of nausea and vomiting on their daily life.

Issue: February 1, 2006

Approved [drawing] The FDA has approved aprepitant (Emend, Merck), in combination with other antiemetics, for the prevention of nausea and vomiting in patients undergoing moderately emetogenic chemotherapy, according to a company press release. The approval was based on the findings of a study that appeared in the Journal of Clinical Oncology.

In the study, researchers compared a regimen of ondansetron and dexamethasone on day 1 followed by aprepitant on day 2 and 3 with a standard regimen of ondansetron and dexamethasone on day 1 followed by ondansetron on day 2 and 3.

Results revealed that a significantly higher proportion of patients treated with the regimen including aprepitant in cycle 1 reported a complete response (no vomiting and no use of other therapies for nausea or vomiting) in the five days after initiation of chemotherapy compared with the standard regimen: 51% and 42%, respectively (P = .015).

In addition, more patients in the aprepitant arm achieved a complete response during the acute (up to 24 hours) and delayed (between 25 and 120 hours) phases compared with patients in the standard regimen arm.

Reduced symptoms

David G. Warr, MD, and colleagues from the Princess Margaret Hospital in Toronto conducted the randomized, double-blind study of 866 emetogenic chemotherapy–naive patients with breast cancer.

They randomized 438 patients to the aprepitant arm and 428 patients to the standard arm. Patients in the study received various chemotherapy regimens: cyclophosphamide, cyclophosphamide plus doxorubicin or epirubicin (Ellence, Pfizer). The most common combination was cyclophosphamide plus doxorubicin.

Patients in the aprepitant arm received 125 mg of oral aprepitant one hour prior to chemotherapy, 8 mg of oral ondansetron 30 to 60 minutes before chemotherapy, 8 mg of ondansetron eight hours after the first ondansetron dose and 12 mg of oral dexamethasone 30 minutes before chemotherapy on day 1. They received 80 mg of aprepitant once daily in the morning on days 2 and 3.

Patients in the standard arm received 8 mg of ondansetron 30 to 60 minutes before chemotherapy, 20 mg of dexamethasone 30 minutes before chemotherapy and 8 mg of ondansetron 8 hours after the first ondansetron dose on day 1. They received 8 mg of ondansetron every 12 hours on days 2 and 3. Patients reported incidences of nausea, vomiting and use of other medications for nausea or vomiting in a diary for five days.

Sixty-four percent of patients receiving aprepitant reported minimal or no effect of nausea and vomiting on their daily life compared with 56% of patients receiving the standard regimen.

After the first cycle, adverse events were comparable between the treatment arms. Extent of hair loss, fatigue or headache was the same or worse than with the aprepitant. The adverse experience profile was generally comparable with the highly emetogenic chemotherapy studies.

For more information:
Warr DG, Hesketh PJ, Gralla RJ, et al. Efficacy and tolerability of aprepitant for the prevention of chemotherapy-induced nausea and vomiting in patients with breast cancer after moderately emetogenic chemotherapy. J Clin Oncol. 2005;23:2822-2830.