Nausea and vomiting are among the most distressing side effects associated with chemotherapy for cancer patients. The search for the best way to prevent these symptoms is ongoing. The development of a group of drugs that act as highly selective antagonists for the serotonin (5-HT3) receptors which may trigger the symptoms was a major step forward. These anti-emetic drugs, called serotonin receptor agonists (5-HT3 RAs, for short), gave better control than a commonly used drug, metoclopramide.
Today, the use of 5-HT3 RAs in the patient's treatment plan, either alone or in combination with other drugs, is regarded as the 'gold standard' alongside chemotherapy that is known to cause many patients to experience nausea and vomiting. There are several 5-HT3 RAs, and although they have different chemical structures they all work in similar ways by blocking the serotonin receptors. However, it is worthwhile knowing if there are important differences in the effects of 5-HT3 RAs, which include ondansetron, granisetron, tropisetron, dolasetron and palonosetron. This systematic review set out to compare these drugs to see if one of them is more effective. However, we found only a small number of trials evaluating tropisetron, dolasetron, ramosetron and palonosetron, so we cannot be sure about how they rank against the other drugs. Most of the trials compared granisetron versus ondansetron and so we were only able to combine the results of trials of this comparison. We found that the effects of granisetron and ondansetron were similar. We were able to study their effects on several outcomes and found similarities for acute vomiting, acute nausea, combined acute nausea and vomiting, delayed vomiting, delayed nausea and the combination of delayed vomiting and nausea. The two drugs were also similar for adverse events, including common side effects such as headache and diarrhoea, with the possible exception of less constipation with the use of ondansetron. This evidence shows that ondansetron and granisetron can be regarded as equivalent drugs for the prevention of acute and delayed nausea and vomiting for patients receiving chemotherapy. There is not enough evidence to know whether any of the different 5-HT3 RAs have similar or different effects. Therefore, the choice of which 5-HT3 RA to use for the prevention of acute nausea and vomiting should be influenced by local conditions, including the costs of the drugs and the ease with which they can be provided. One large study of 1114 participants comparing palonosetron plus dexamethasone versus granisetron plus dexamethasone showed palonosetron to be better at controlling delayed vomiting and delayed nausea. Palonosetron and dexamethasone combined appeared to be good at delaying nausea and vomiting. As the results from a single trial are limited, and also because another trial comparing palonosetron with ondansetron showed a lack of benefit, however, further evidence is needed before palonosetron can be recommended as the 5-HT3 RA of choice for the prevention of delayed nausea and vomiting.