Prophylaxis of radiation-induced nausea and vomiting using 5-hydroxytryptamine-3 serotonin receptor antagonists: a systematic review of randomized trials

Int J Radiat Oncol Biol Phys. 2012 Jan 1;82(1):408-17. doi: 10.1016/j.ijrobp.2010.08.060. Epub 2010 Nov 13.


Purpose: To systematically review the effectiveness and safety of 5-hydroxytryptamine-3 receptor antagonists (5-HT3 RAs) compared with other antiemetic medication or placebo for prophylaxis of radiation-induced nausea and vomiting.

Methods and materials: We searched the following electronic databases: MEDLINE, Embase, the Cochrane Central Register of Controlled Clinical Trials, and Web of Science. We also hand-searched reference lists of included studies. Randomized, controlled trials that compared a 5-HT3 RA with another antiemetic medication or placebo for preventing radiation-induced nausea and vomiting were included. We excluded studies recruiting patients receiving concomitant chemotherapy. When appropriate, meta-analysis was conducted using Review Manager (v5) software. Relative risks were calculated using inverse variance as the statistical method under a random-effects model. We assessed the quality of evidence by outcome using the Grading of Recommendations Assessment, Development, and Evaluation approach.

Results: Eligibility screening of 47 articles resulted in 9 included in the review. The overall methodologic quality was moderate. Meta-analysis of 5-HT3 RAs vs. placebo showed significant benefit for 5-HT3 RAs (relative risk [RR] 0.70; 95% confidence interval [CI] 0.57-0.86 for emesis; RR 0.84, 95% CI 0.73-0.96 for nausea). Meta-analysis comparing 5-HT3 RAs vs. metoclopramide showed a significant benefit of the 5-HT3 RAs for emetic control (RR 0.27, 95% CI 0.15-0.47).

Conclusion: 5-Hydroxytryptamine-3 RAs are superior to placebo and other antiemetics for prevention of emesis, but little benefit was identified for nausea prevention. 5-Hydroxytryptamine-3 RAs are suggested for prevention of emesis. Limited evidence was found regarding delayed emesis, adverse events, quality of life, or need for rescue medication. Future randomized, controlled trials should evaluate different 5-HT3 antiemetics and new agents with novel mechanisms of action such at the NK(1) receptor antagonists to determine the most effective drug. Delayed nausea and vomiting should be a focus of future study, perhaps concentrating on the palliative cancer population.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Antiemetics / therapeutic use*
  • Humans
  • Metoclopramide / therapeutic use
  • Nausea / etiology
  • Nausea / prevention & control*
  • Radiotherapy / adverse effects*
  • Randomized Controlled Trials as Topic
  • Serotonin 5-HT3 Receptor Antagonists / therapeutic use*
  • Vomiting / etiology
  • Vomiting / prevention & control*


  • Antiemetics
  • Serotonin 5-HT3 Receptor Antagonists
  • Metoclopramide