The U.S. Food and Drug Administration (FDA) has approved palonosetron hydrochloride (Aloxi) injection for the prevention of acute nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including highly emetogenic cancer chemotherapy, in children aged 1 month to less than 17 years. This is the first approval of a product for acute chemotherapy-induced nausea and vomiting prevention in patients aged 1 month to 6 months. The age of peak cancer incidence among children occurs within the first year of life, so this approval offers an important option to children, and especially infants, undergoing chemotherapy.
Chemotherapy-induced nausea and vomiting is among the most common side effects following therapy in patients with cancer. In clinical trials, chemotherapy-induced nausea and vomiting has been seen in 35% to 80% of pediatric patients.
Clinical Trial Details
In response to a written request from the FDA, Helsinn Group conducted four pediatric clinical trials with palonosetron hydrochloride. The approval was based on a randomized, double-blind, noninferiority pivotal trial comparing single-dose intravenous (IV) palonosetron hydrochloride at 20 µg/kg given 30 minutes prior to chemotherapy to a standard of care IV ondansetron regimen of 0.15 mg/kg given 30 minutes prior to chemotherapy followed by infusions 4 and 8 hours after the first dose of ondansetron. The primary endpoint of the study was complete response, defined as no vomiting, no retching, and no antiemesis rescue medication.
Within the first 24 hours after chemotherapy, complete response was achieved in 59.4% of patients who received palonosetron hydrochloride at 20 µg/kg vs 58.6% of those who received the ondansetron regimen.
Treatment-emergent adverse events were comparable across both arms, with the most frequently reported adverse event in the palonosetron group being headaches. While this study demonstrated that pediatric patients require a higher palonosetron dose than adults to prevent chemotherapy-induced nausea and vomiting, the safety profile is consistent with the established profile in adults. ■