5-HT3 receptor antagonists in chemotherapy-induced nausea and vomiting

Evidence Summaries

Level of Evidence = A
5-HT3 receptor antagonists alone or combined with steroids are effective for chemotherapy induced nausea and vomiting compared to placebo.

A systematic review 1 including 41 studies was abstracted in DARE. The odds ratios were as follows:

  • 5-HT3 vs high-dose metoclopramide following cisplatin therapy: 0.60 (95% CI 0.51 to 0.70).
  • 5-HT3 vs conventional anti-emetics following low-dose cisplatin chemotherapy: 0.28 (95% CI 0.17 to 0.44).
  • 5-HT3 vs conventional anti-emetics following moderately emetogenic chemotherapy: 0.47 (95% CI 0.39 to 0.58).
  • 5-HT3 vs 5-HT3 + dexamethasone following cytotoxic chemotherapy: 0.42 (95% CI 0.34 to 0.51). There was no difference between 5-HT3 and dexamethasone.

Another systematic review and network meta-analysis 2 on 5-HT3 receptor antagonists (dolasetron, granisetron, ondansetron, palonosetron, tropisetron) for patients undergoing chemotherapy included 299 studies with a total of 58,412 subjects.

In the network meta-analysis, all 5-HT3 receptor antagonists were effective for reducing risk of nausea (44 studies, n=11,664, 12 treatments), vomiting (63 studies, n=15,460, 12 treatments), and chemotherapy-induced nausea or vomiting (27 studies, n=10,924, 9 treatments) compared to placebo. All treatments decreased the risk of severe vomiting (10 studies, n=917), but only ondansetron and ramosetron were significantly superior to placebo. According to the rank-heat plot, palonosetron + steroid was most likely the safest and most effective treatment. Across the effectiveness outcomes, the following treatments ranked as most superior on 3 effectiveness outcomes during the first 24 h after chemotherapy for adults: ondansetron + steroid, palonosetron + steroid, granisetron + steroid, and ramosetron + steroid.


1. Jantunen IT, Kataja VV, Muhonen TT. An overview of randomised studies comparing 5-HT3 receptor antagonists to conventional anti-emetics in the prophylaxis of acute chemotherapy-induced vomiting. Eur J Cancer 1997 Jan;33(1):66-74.  [PMID:9071902]

2. Tricco AC, Blondal E, Veroniki AA et al. Comparative safety and effectiveness of serotonin receptor antagonists in patients undergoing chemotherapy: a systematic review and network meta-analysis. BMC Med 2016;14(1):216.  [PMID:28007031]

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