Oral serotonin type 3-receptor antagonists for prevention of chemotherapy-induced emesis

The theoretical basis for and clinical experience with using oral serotonin . type 3 (5-HT3)-receptor antagonists for preventing chemotherapy-induced e mesis are discussed. evidence supports the idea that anti-neoplastic drugs and irradiation can i nitiate emesis by releasing serotonin from enterochromaffin cells in the gu t mucosa, which activates peripheral vagal afferent nerves. In view of the GI site of serotonin release and vagal afferent activation, the proximity o f neuronal 5-HT3 receptors, and the pharmacologic properties of 5-HT3-recep tor antagonists, the oral use of these agents is rational. Oral granisetron 2 mg once daily or 1 mg twice daily has been evaluated in more than 4500 p atients receiving highly or moderately emetogenic chemotherapy. Rates of to tal control of emesis ranged from 44% to 60%, and complete-response rates r anged from 70% to 94%. Oral ondansetron 8 mg three times daily has proven e ffective in patients receiving antineoplastics with moderate or moderately high emetogenic potential. Two double-blind studies demonstrated the effica cy of single 24-mg oral dose of ondansetron administered approximately 30 m inutes before cisplatin-based chemotherapy. Patients randomized to oral ond ansetron had higher total-control and complete-response rates that patient receiving intravenous granisetron or ondansetron. Oral dolasetron 100 or 20 0 mg once daily also prevented emesis. Oral administration of 5-HT3-receptor antagonists for the prevention of acu te emesis associated with chemotherapy is rational and appears to be effect ive.