Oral Serotonin Type 3-Receptor Antagonists For Prevention of Chemotherapy-Induced Emesis

Celeste Lindley and Peter Blower


Am J Health Syst Pharm. 2000;57(18) 

In This Article

Abstract and Introduction

The theoretical basis for and clinical experience with using oral serotonin type 3 (5-HT3)-receptor antagonists for preventing chemotherapy-induced emesis are discussed.

Evidence supports the idea that antineoplastic drugs and irradiation can initiate emesis by releasing serotonin from enterochromaffin cells in the gut mucosa, which activates peripheral vagal afferent nerves. In view of the GI site of serotonin release and vagal afferent activation, the proximity of neuronal 5-HT3 receptors, and the pharmacologic properties of 5-HT3-receptor 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 patients receiving highly or moderately emetogenic chemotherapy. Rates of total control of emesis ranged from 44% to 60%, and complete- response rates ranged from 70% to 94%. Oral ondansetron 8 mg three times daily has proven effective in patients receiving antineoplastics with moderate or moderately high emetogenic potential. Two double-blind studies demonstrated the efficacy of a single 24-mg oral dose of ondansetron administered approximately 30 minutes before cisplatin-based chemotherapy. Patients randomized to oral ondansetron had higher total-control and complete-response rates than patients receiving intravenous granisetron or ondansetron. Oral dolasetron 100 or 200 mg once daily also prevented emesis.

Oral administration of 5-HT3-receptor antagonists for the prevention of acute emesis associated with chemotherapy is rational and appears to be effective.

The management of chemotherapy- induced nausea and vomiting has improved significantly during the past 10 years. Not only has considerable progress been made in developing serotonin type 3 (5- HT3 )-receptor antagonists, but our understanding of the mechanisms of chemotherapy-induced emesis has been greatly enhanced. The hind-brain chemoreceptor trigger zone (CTZ), long believed to be the primary trigger site of the emetic response, is now thought to play a secondary role. Results of vagotomy, neuronal activation, and x-irradiation studies suggest that the primary site of activation may be located in the abdomen.

This article reviews data supporting a peripheral mechanism for activation of emesis caused by cytotoxic drugs and irradiation. On the basis of this model, a case for oral administration of 5-HT3-receptor antagonists is made. Clinical studies of oral 5-HT3-receptor antagonists for prevention of emesis are discussed.