A risk-benefit assessment of serotonin 5-HT₃ receptor antagonists in antineoplastic therapy-induced emesis

Insight into the pathophysiology of antineoplastic therapy-induced nausea and vomiting led to the development of the serotonin 5-HT₃ receptor antagonists as the most potent class of antiemetic agents. Among those which have been investigated are ondansetron, granisetron, tropisetron and dolasetron. A risk-benefit analysis of these drugs must not only account for the modest clinical differences in efficacy and tolerability, but also should include such issues as ease of use, route of administration, dosage considerations and patient preference. Pharmacokinetic and preclinical studies reveal distinctions among these antiemetics, but, overall, these distinctions do not translate in to clinically significant differences. In clinical trials, the most widely studied members of the 5-HT₃ receptor antagonists are granisetron and ondansetron, which have been found to possess equivalent antiemetic efficacy. Dolasetron and tropisetron are also available, and some randomised trials have also documented their similar antiemetic activity, depending on the doses and schedules used. The equivalent efficacy of oral granisetron 2 mg versus intravenous ondansetron 32 mg has recently been demonstrated in prospective randomised clinical trials in patients receiving either highly emetogenic or moderately emetogenic antineoplastic therapy. The utilisation and efficacy of oral ondansetron and dolasetron in patients receiving moderately emetogenic antineoplastic therapy has also been documented. This review offers a brief overview of the pharmacokinetic and preclinical research on the 5-HT₃ antagonists, a review of the comparative clinical trials of the major members of this class and a summary risk-benefit assessment that considers clinical applicability and cost, as well as efficacy and safety.