Aprepitant (
Emend) is the first commercially available
drug from a new class of agents, the neurokinin
NK(1) receptor antagonists. Oral
aprepitant, in combination with other agents, is indicated for the prevention of acute and delayed
chemotherapy-induced
nausea and
vomiting (CINV) associated with highly emetogenic
chemotherapy in adults. In three randomised, double-blind, placebo-controlled trials comparing
aprepitant (125 mg day 1, 80mg once daily on days 2 and 3 or 2-5) plus standard
therapy (intravenous
ondansetron and oral
dexamethasone) with standard
therapy plus placebo, overall complete responses (primary endpoint, defined as no
emesis and no rescue
therapy) were seen in significantly more patients in the
aprepitant arms (63-73% versus 43-52%, p < 0.01 for all comparisons). Complete responses and complete protection during the acute and delayed phase, and overall complete protection were also observed in significantly more patients in the
aprepitant arms. The difference between treatment groups was more marked in the overall and delayed phases than in the acute phase. The
antiemetic efficacy of
aprepitant plus standard
therapy in the prevention of CINV was maintained for up to six cycles of
chemotherapy. Where assessed, more patients in the
aprepitant plus standard
therapy arms than the standard
therapy plus placebo arms reported no impact of CINV on daily life, as assessed by the Functional Living Index-
Emesis.
Aprepitant is generally well tolerated. The most common adverse events in randomised trials were
asthenia or
fatigue. Other adverse events experienced by
aprepitant recipients include
anorexia,
constipation, diarrhoea,
nausea (after day 5 of the study) and
hiccups. In addition to being a substrate for
cytochrome P450 (CYP) 3A4,
aprepitant is also a moderate inhibitor and inducer of this
isoenzyme as well as an inducer of
CYP2C9. Thus,
aprepitant has the potential to interact with other agents metabolised by hepatic CYP
isoenzymes. In one trial, there was a higher incidence of serious
infection or
febrile neutropenia in the
aprepitant plus standard
therapy arm than the standard
therapy plus placebo arm; this was attributed to a pharmacokinetic interaction between
aprepitant and
dexamethasone. In subsequent trials, a modified
dexamethasone regimen was used. In conclusion, when added to standard
therapy (a
serotonin 5-HT(3) receptor antagonist and a
corticosteroid),
aprepitant is effective and generally well tolerated in the prevention of CINV associated with highly emetogenic
chemotherapy in adults. Despite marked advances in the prevention of CINV, standard
therapy does not protect all patients. The addition of
aprepitant to standard
therapy provides an advance in the prevention of both acute and delayed CINV in adults with
cancer.