Serotonin receptor antagonists for highly emetogenic chemotherapy in adults

BackgroundSerotonin receptor antagonists (5-HT3 RAs) are used to control chemotherapy-induced emesis. Although they have the same general mechanism of action (blockade of serotonin receptors), they have different chemical structures and may have different effects.ObjectivesTo compare efficacy of different serotonin receptor antagonists (5-HT3 RAs) in the control of acute and delayed emesis induced by highly emetogenic chemotherapy.Search strategyWe searched CENTRAL, the Specialised Register of the Cochrane PaPaS Group, PubMed, EMBASE, and LILACS databases. Our most recent search was in March 2009.Selection criteriaRandomised trials comparing 5-HT3 RAs in an adult cancer population.Data collection and analysisWe extracted information from the included studies on the control of acute and delayed nausea and vomiting, either as a single or a combined outcome. Where appropriate, we combined the results of similar trials. We carried out sensitivity and subgroup analyses to test the robustness of our findings.Main resultsWe included 16 randomised trials (7808 participants). Nine of the trials compared granisetron versus ondansetron. No other drug comparison was studied in more than one trial. The meta-analyses of the granisetron versus ondansetron trials found similar results for the two drugs on acute vomiting (eight trials, 4256 participants, odds ratio (OR) 0.89; 95% CI 0.78 to 1.02), acute nausea (seven trials, 4160 participants, OR 0.97; 95% CI 0.85 to 1.10), delayed vomiting (three trials, 1119 participants, OR 1.00; 95% CI 0.74 to 1.34) and delayed nausea (two trials, 1024 participants, OR 0.96; 95% CI 0.75 to 1.24). Granisetron and ondansetron showed similar effects on headache and diarrhoea, with the possible exception of less constipation associated with ondansetron.One study of 1114 participants comparing palonosetron plus dexamethasone versus granisetron plus dexamethasone showed superiority of palonosetron in controlling delayed vomiting (OR 1.45; 95% CI 1.14 to 1.85) and delayed nausea (OR 1.63; 95% CI 1.27 to 2.10). Complete response for delayed nausea and vomiting was also in favour of the combination palonosetron and dexamethasone (OR 1.63; 95% CI 1.29 to 2.07).Authors' conclusionsOndansetron and granisetron appear to be equivalent drugs for the prevention of acute and delayed emesis following the use of highly emetogenic chemotherapy.According to one single trial the combination of palonosetron and dexamethasone was superior to granisetron and dexamethasone in controlling delayed emesis. However, more evidence is needed before palonosetron could become the candidate 5-HT3 RA for the control of delayed emesis induced by highly emetogenic chemotherapy.