Chemotherapy-induced
nausea and
vomiting (CINV) is a distressing and common adverse event associated with
cancer treatment. Updated
anti-emetic guidelines were published in 2007 by the National Comprehensive
Cancer Network and in 2006 by the American Society of Clinical Oncology, which have included the use of the new and more effective
anti-emetic agents (
5-hydroxytryptamine-3 [5-HT(3)] receptor antagonists and neurokinin-1 [
NK-1] receptor antagonists).
Aprepitant is a selective
NK-1 receptor antagonist approved as part of combination
therapy with a
corticosteroid and a 5-HT(3) receptor antagonist for the prevention of acute and delayed CINV.
Fosaprepitant (also known as
MK-0517 and L-758,298) is a water-soluble phosphoryl
prodrug for
aprepitant, which, when administered intravenously, is converted to
aprepitant within 30 min after
intravenous administration via the action of ubiquitous
phosphatases. Because
fosaprepitant is rapidly converted to the active form (
aprepitant), it is expected to provide the same
aprepitant exposure in terms of AUC, and a correspondingly similar
anti-emetic effect. Clinical studies have suggested that
fosaprepitant could be appropriate as an intravenous alternative to the
aprepitant oral
capsule. In a study in healthy subjects,
fosaprepitant was well tolerated up to 150 mg (1 mg/ml), and
fosaprepitant 115 mg was bioequivalent in its AUC to
aprepitant 125 mg.
Fosaprepitant 115 mg has been submitted for FDA approval as an alternative on day 1 of a 3-day oral
aprepitant regimen, with oral
aprepitant administered on days 2 and 3.
Fosaprepitant may be a useful parenteral alternative to oral
aprepitant. Further study is needed to clarify the use of
fosaprepitant for the prevention of CINV, and to clarify optimal dosing regimens that may be appropriate substitutes for oral
aprepitant.