for effective prophylaxis and
management of CINV include
5-hydroxytryptamine-3 (5-HT 3
receptor antagonists (RAs),
neurokinin-1 (NK 1 ) RAs and
glucocorticosteroids (mainly
dexamethasone).
A wide variety of other
antiemetic agents are available,
which can all be classified
according to the therapeutic index
of their usefulness.
Agents with a high therapeutic
index
Serotonin receptor antagonists
(5-HT 3 RAs)
The introduction of selective 5-HT 3
RAs (‘setrons’) in the early 1990s
revolutionised prevention and
management of CINV. Before their
introduction, only limited effective
options were available. 1,3
Serotonin is released by
entero-endocrine cells in
the gastrointestinal tract
following administration of
chemotherapeutic agents. 5-HT 3
RAs act by binding to 5-HT 3
receptors and are highly effective
for prevention and treatment of
CINV. 3
Currently, the following
5-HT 3 RAs are available (varying
according to the region):
ondansetron, granisetron,
tropisetron, dolasetron,
ramosetron, azasetron (all first
generation) and palonosetron
(second generation).
They are still considered
to be the cornerstone of
standard antiemetic therapy for
control of acute emesis with
chemotherapeutic agents with
moderate to high emetogenic
potential.
‘Setrons’ are the most effective
antiemetics in the prophylaxis
of acute CINV, are widely used,
and continue to provide effective
management of CINV. They are
particularly important in the
pathophysiology of acute vomiting
and rarely require discontinuation
of therapy. 1,3,10–16
Palonosetron exhibits a unique
pharmacological profile compared
with other 5-HT 3 RAs, which could
offer a potential explanation of its
exceptional clinical efficacy with
respect to other ‘setrons’, and also
its activity in delayed CINV. 1,3
Cytochrome P450 (CYP)
enzymes are involved in the
hepatic metabolism of 5-HT 3
RAs. The CYP isoform on which
metabolism relies most varies for
the different setrons (for example,
granisetron is predominantly
metabolised via CYP3A4, whereas
tropisetron and dolasetron
are mainly metabolised via
CYP2D6). 1,3,11–16
The relation with emetic
response, 5-HT 3 kinetics and
genetic polymorphisms have
been described. CYP enzyme
polymorphism might be beneficial
for conversion to an alternate 5-HT 3
RA and could benefit 40–50% of
patients who did not respond to
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