Palonosetron effective anti-emetic for paediatric chemotherapy patients

Jan 26 2016

By Shreeya Nanda, Senior medwireNews Reporter

Palonosetron 20 μg/kg is noninferior to ondansetron for the control of chemotherapy-induced vomiting and nausea during the acute phase of the first treatment cycle in paediatric patients with cancer, research shows.

“These results led to the approval of the 20 μg/kg dose of palonosetron by both the US FDA [Food and Drug Administration] and the European Medicines Agency for the prevention of chemotherapy-induced nausea and vomiting in paediatric cancer patients aged 1 month to younger than 17 years undergoing initial or repeated courses of moderately or highly emetogenic chemotherapy”, the team writes in The Lancet Oncology.

In this double-blind trial, 59% of 165 patients randomly assigned to receive palonosetron 20 μg/kg on day 1 of a single- or multi-day chemotherapy regimen achieved a complete response – defined as no vomiting, retching or use of anti-emetic rescue medication during the initial 24 hours of chemotherapy.

And although the complete response rate was an identical 59% among the 162 patients given three 150 μg/kg doses of ondansetron, the weighted sum of the differences in complete response rates was 0.36% and the lower limit of the 97.5% confidence interval was –11.7%, which was higher than the predefined noninferiority margin of –15%.

Gábor Kovács (Semmelweis University, Budapest, Hungary) and co-authors also assessed palonosetron 10 μg/kg, randomly assigning 166 participants to receive the 5-HT₃ receptor antagonist at this dose, but they could not demonstrate noninferiority versus ondansetron.

During the delayed phase (24–120 h after the initiation of chemotherapy), complete responses were observed in 39% of patients in the palonosetron 20 μg/kg arm and 28% of those in the ondansetron arm, giving a weighted sum of differences of 10.17%. These findings suggest “that the efficacy of this dose of palonosetron during the delayed phase might be superior to that of ondansetron”, say the researchers, but they caution that the trial was not powered for a superiority analysis.

And in a linked comment, L Lee Dupuis (The Hospital for Sick Children, Toronto, Ontario, Canada) points out that the emetic stimulus was not controlled from day 2 to 6, and therefore, the contribution of palonosetron on delayed control chemotherapy-induced vomiting and nausea “remains unknown”.

She adds that interpretation of the study findings is also limited by the lack of stratification of randomisation by receipt of dexamethasone – given at the physician’s discretion – and the absence of uniformity in its dosing.

However, the commentator underscores “that there were no safety signals” among the palonosetron-treated children in the trial.

The incidence of treatment-emergent adverse events during the first on-study treatment cycle was lower in the palonosetron 20 μg/kg group than in the palonosetron 10 μg/kg and ondansetron groups, at 69% versus 80% and 82%, respectively. This was also the case for serious adverse events, with corresponding rates of 26% versus 31% and 34%, respectively.

Headache was the most common drug-related side effect, occurring in a respective one, three and two participants in the palonosetron 20 μg/kg, palonosetron 10 μg/kg and ondansetron arms.

And no patient discontinued or died as a result of drug-related treatment emergent adverse events.

L Lee Dupuis therefore concludes that the results “reassure clinicians of the safety of palonosetron in children and of its efficacy in preventing acute phase vomiting in children receiving 1-day moderately emetogenic chemotherapy or highly emetogenic chemotherapy.

“Future studies will determine whether the benefits of palonosetron reported in adults with cancer—namely, improved nausea and delayed phase chemotherapy-induced nausea and vomiting control—will also be realised in children.”

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