Botrel, T.E., Clark, O.A., Clark, L., Paladini, L., Faleiros, E., & Pegoretti, B. (2010). Efficacy of palonosetron (PAL) compared to other serotonin inhibitors (5-HT3R) in preventing chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately or highly emetogenic (MoHE) treatment: Systematic review and meta-analysis. Supportive Care in Cancer, 19, 823–832.

To analyze randomized, controlled trials (RCTs) comparing a single IV palonosetron dose to other serotonin antagonists for prevention of chemotherapy-induced nausea and vomiting (CINV)

Databases searched were Embase, LILACS, MEDLINE, SCI, CENTRAL, National Cancer Institute Clinical Trials service, Clinical Trials Register of Trials Central, American Society of Clinical Oncology, and American Society of Hematology and European Society for Medical Oncology abstracts.

Search keywords were palonosetron, random, chemotherapy, clinical trial, meta-analysis, practice guideline, randomized controlled trial, and review.

Studies were included in the review if they

• Were RCTs with parallel design that compared a single IV dose of palonosetron with other 5-HT₃ receptor antagonists (RAs) in patients receiving chemotherapy.
• Reported on patients receiving moderately or highly emetogenic chemotherapy regimens.

Initially, 324 references were identified. Five trials were used for final analysis. Two independent reviewers extracted study data and evaluated study quality and risk of bias. No specific methodology for this was described.

• The final sample was five studies involving 2,057 patients.
• Study sample sizes ranged from 50 to 667 participants.
• In three studies, use of corticosteroids was not allowed, and, in one study, corticosteroids were used concomitantly in a few patients.
• In all but one study, the primary endpoint was complete response during the acute phase.

• Overall from 0 to 120 hours, palonosetron was superior in the prevention of vomiting (relative risk [RR] = 0.79; confidence interval [CI] = 95%, 0.72–0.88; p < 0.00001).
• Palonosetron was more effective than other 5-HT₃ RAs in preventing acute vomiting (RR = 0.76; CI = 95%, 0.66–0.88, p = 0.0002) as well as late vomiting (RR = 0 0.76; CI = 95%, 0.68–0.85; p < 0.00001).
• Substantial heterogeneity was found (p < 0.05); however the superiority of palonosetron remained when one trial was removed from analysis with reduction in heterogeneity.
• In the study that used corticosteroids, no difference was found between palonosetron and other 5-HT₃ RAs.

• Palonosetron was more effective than other 5-HT₃ RAs for the prevention of acute and delayed CINV, when the drug regimen did not include corticosteroids.
• No difference in efficacy was found when other 5-HT₃ RAs were used in combination with a corticosteroid.

• Despite guidelines and recommendations that include the use of steroids, four out of the five trials included did not incorporate these.
• No subgroup analysis could be done between moderately and highly emetogenic chemotherapy regimens; therefore, it is not known if different CINV prevention regimens have different efficacy based on this factor.