Nausea and
vomiting are considered to be among the most distressing consequences of cytotoxic
chemotherapies. Currently, there are several novel 5-HT(3) receptor antagonists for the treatment of
chemotherapy-induced
nausea and
vomiting (CINV), including
ondansetron,
granisetron, and
dolasetron. These agents provide significant improvement in the management of acute
emesis but are ineffective at preventing delayed
emesis. In 2003, a new 5-HT(3) receptor antagonist,
palonosetron HCL (
Aloxi), was introduced to the U.S. market.
Palonosetron was found to be effective in preventing delayed CINV. Indeed,
palonosetron was the first and only 5-HT(3) receptor antagonist approved by the FDA for the prevention of both acute and delayed CINV. More recently, studies on the role of
substance P in the
emetic process led to the development of
aprepitant (
Emend) for the prevention of delayed
emesis in combination with 5-HT(3) receptor antagonists. Despite these major advances, CINV remains uncontrolled in some patients. Current efforts are focused on treating refractory
emesis and include both the clinical evaluation of compounds marketed for other indications and the preclinical evaluation of novel molecules targeting other transmitters in the
emetic pathway. Ongoing work in pharmacogenomics has postulated several candidate genes that could be involved in
emetic sensitivity and responsiveness to
antiemetic therapy. Investigations into the pharmacogenomics of CINV may someday be able to aid in the identification of high risk patients and patients unlikely to respond to conventional
therapies.