NEW YORK (Reuters Health) – Combined with ondansetron and dexamethasone, a single intravenous dose of fosaprepitant is as effective as a standard 3-day oral course of aprepitant for preventing chemotherapy-induced nausea and vomiting (CINV), according to a multicenter team of researchers.

Dr. Steven Grunberg, from the University of Vermont in Burlington, and colleagues note in the Journal of Clinical Oncology online March 7 that adding the neurokinin-1 receptor antagonist aprepitant to ondansetron and dexamethasone improves prevention of CINV, particularly in the delayed phase (25-120 hours after chemo).

An analog of aprepitant — fosaprepitant — is rapidly converted to aprepitant after intravenous administration, the researchers explain, and its good therapeutic index should allow higher dosing and hence extended serum levels. As they point out, a single-dose alternative to the 3-day regimen for aprepitant would be convenient and promote adherence.

To test this, the team assigned 2322 patients receiving cisplatin for the first time to receive ondansetron and dexamethasone with a standard aprepitant regimen (125 mg on day 1, 80 mg on day 2, 80 mg on day 3) or a single 150-mg dose of fosaprepitant on day 1. Matched IV or oral placebos were given to maintain double blinding.

The primary end point was complete response, i.e., no vomiting and no rescue medication during the overall risk phase of 0-120 hours. This was achieved by 71.9% of patients in the fosaprepitant group and 72.3% of those in the aprepitant group, according to the report.

“For the secondary efficacy end point of complete response during the delayed phase, 74.3% of patients in the fosaprepitant group reported complete response compared with 74.2% in the aprepitant group,” the investigators found.

Adverse events overall were similar in the two arm of the trial and both regimens were well tolerated. Reactions at the fosaprepitant/placebo infusions site, however, were more frequent in the fosaprepitant group (2.7%) than in those assigned to aprepitant (0.3%).

“This study indicates that a triple-antiemetic regimen containing a single dose of IV fosaprepitant is noninferior to a triple antiemetic regimen containing 3 days of oral aprepitant,” Dr. Grunberg and colleagues conclude. The overall pattern of efficacy and toxicity of fosaprepitant was similar to that of aprepitant, “thereby providing a reasonable and feasible therapeutic alternative.”

Reference:

Single-Dose Fosaprepitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting Associated With Cisplatin Therapy: Randomized, Double-Blind Study Protocol—EASE

J Clin Oncol 2011;29.