Billio, A., Morello, E., & Clarke, M.J. (2010). Serotonin receptor antagonists for highly emetogenic chemotherapy in adults. Cochrane Database of Systematic Reviews (Online), CD006272.

To compare the effectiveness of different 5-HT₃ receptor antagonists (RAs) in the control of acute- and delayed-onset emesis associated with highly emetogenic chemotherapy

Databases searched were Cochrane Register of Clinical Trials (CENTRAL), PubMed, Embase, and Latin American and Caribbean Health Sciences Literature (LILACS).

Search keywords were MeSH for granisetron; ondansetron, tropisetron, dolasetron, ramosetron, palonosetron, azasetron, in all possible comparison sets; chemotherapy, antineoplastic agents, and cisplatin. Internet databases of gray literature were searched, and hand searching was performed of potentially relevant journals and conference proceedings.

Studies were included in the review if they

• Were randomized controlled trials (RCT) comparing different 5-HT₃ RAs in adults with cancer.
• Had at least 20 participants per treatment group.
• Reported on patients older than 16 years.
• Reported on patients receiving cytotoxic drugs for which emesis is expected in more than 90% of administrations according to American Society of Clinical Oncology (ASCO) emetic risk classification (2006).

Studies were excluded if they 

• Had insufficient concealment of allocation in the study procedures.
• Included patients with nausea and vomiting associated with moderately emetogenic chemotherapy, radiotherapy, surgery, or bone marrow transplant.

Of the 25 studies found that met the eligibility criteria, 16 RCTs were included. These studied granisetron, ondansetron, tropisetron, ramosetron, palonosetron, and dolasetron. Four studies were excluded because of inadequate outcome assessment, two studies because of the unavailability of the protocol, one study because of very poor methodological quality, and one study because it included patients receiving only moderately emetogenic therapy.

The final sample of 16 studies reported on 7,808 patients across all studies.

Acute nausea

• Pooled data from seven studies (involving 4,160 participants) that evaluated granisetron versus ondansetron were included.
• Pooled results favored ondansetron (odds ratio [OR] = 0.97, confidence interval [CI] = 95%, 0.85–1.10).

Total control of acute nausea and vomiting

• Data from six studies of granisetron versus ondansetron, involving 2,809 patients in total, were included.
• No significant differences were found with respect to different 5‑HT₃ RAs or any other factors.

Delayed nausea

• Data were combined and analyzed from two studies with a total of 1,024 patients.
• Palonosetron appeared to be superior to granisetron in controlling delayed nausea.
• Both drugs were given in combination with dexamethasone (OR = 1.63, CI = 95%; 1.27–2.10).

Total control of delayed nausea and vomiting

• Data were pooled and analyzed from two studies involving 1,045 patients.
• Palonosetron was superior to granisetron.

Meta-analysis of granisetron and ondansetron

• Both had similar effects on either acute or delayed nausea and vomiting.
• Both had similar side effects.

• Ondansetron and granisetron were essentially equivalent for prevention of acute and delayed nausea and vomiting with highly emetogenic chemotherapy.
• No 5-HT₃ RA appeared to be superior to any other for acute nausea.
• Palonosetron plus dexamethasone may perform better than others for delayed nausea and vomiting; however, this was shown by a single study and more evidence should be obtained in this area before a firm recommendation can be made.
• Findings suggested that 5-HT₃ RAs are equally effective for management of nausea and vomiting with highly emetogenic chemotherapy.
• Some suggested differences were found in terms of side effect profiles and effectiveness for delayed nausea.

Further RCTs comparing palonosetron and dexamethasone for delayed nausea are warranted.