Section Review: Central & Peripheral Nervous Systems: 5-HT₃ receptor antagonists as antiemetic agents in cancer chemotherapy

Abstract

Emesis is a serious and poorly tolerated side-effect of cancer chemotherapy. Highly emetogenic agents (e.g., cisplatin, dacarbazine) and combination chemotherapy have been used frequently since the end of the 1970s. The introductions of high-dose metoclopramide and corticosteroid-containing antiemetic cocktails at the beginning of the 1980s were important improvements. The discovery of the 5-HT₃ receptors and the synthesis of their antagonists (e.g., ondansetron, granisetron, tropisetron) in the mid 1980s signified a great breakthrough in antiemetic research and therapy. Acute nausea and vomiting are well controlled by these new drugs in 80 — 90% of cases; combination with a corticosteroid further improves their efficacy. However, the value of 5-HT₃ receptor antagonists in the prevention of delayed emesis following highly emetogenic chemotherapy remains controversial. Further studies are needed to settle this question definitively. A number of new 5-HT₃ antagonists are in Phase I-Ill development; however, to date, no major improvements over the currently established drugs have been demonstrated. Despite a rather high acquisition cost, 5-HT₃ receptor antagonists should be used as standard antiemetic treatment in most types of emetogenic cancer chemotherapy.