Kovacs, G., Wachtel, A.E., Basharova, E.V., Spinelli, T., Nicolas, P., & Kabickova, E. (2016). Palonosetron versus ondansetron for prevention of chemotherapy-induced nausea and vomiting in paediatric patients with cancer receiving moderately or highly emetogenic chemotherapy: A randomised, phase 3, double-blind, double-dummy, non-inferiority study. Lancet Oncology, 17, 332–344.

To assess the efficacy and safety of palonosetron versus ondansetron in the prevention of chemotherapy-induced nausea and vomiting (CINV) in pediatric patients receiving moderately (MEC) or highly emetogenic chemotherapy (HEC)

Four cycles of 10 mc/kg palonosetron was compared to three 150 mc/kg doses of ondansetron on day 1 of chemotherapy, and 20 mc/kg palonosetron was compared to three 150 mc/kg doses of ondansetron on day 1 of chemotherapy. The intervention assignment was stratified based on the age of the participant and the emetogenicity of the chemotherapy. The efficacy of antiemetic regimens was evaluated through the proportion of patients who achieved complete response (CR) (no vomiting, retching, or use of rescue drugs) during the acute phase (0–24 hours post chemotherapy) of chemotherapy on day 1. Safety was evaluated through the number of adverse events reported.

• N = 493   
• AGE RANGE = 2.1 months–16.9 years
• MEAN AGE = 8.21 years
• MALES: 53.1%, FEMALES: 46.9%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: No specific type of cancer required for inclusion
• OTHER KEY SAMPLE CHARACTERISTICS: MEC or HEC

• SITE: Multi-site   
• SETTING TYPE: Not specified    
• LOCATION: United States, South America, and Europe

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Pediatrics

• Double-blind, double-dummy, phase-III study

• Episodes of CINV, retching, and rescue medications used were documented in a daily diary kept by the patient/caregiver.  
• Adverse events were measured through physical examination, vital signs, laboratory assessments, and 12-lead electrocardiograms. The severity of all adverse events was rated mild, moderate, or severe based on the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03.

Twenty mc/kg palonosetron resulted in a significantly higher proportion of patients who achieved CR (no vomiting, retching, or use of antiemetic rescue medication) on day 1 of chemotherapy compared to those who received ondansetron (p = 0.0022). No difference existed in the proportion of CR on day 1 of chemotherapy for those who received 10 mc/kg palonosetron compared to ondansetron. Adverse events were reported in 80% (n = 134) of patients who received 10 mc/kg palonosetron, 69% (n = 113) of those who received 20 mc/kg palonosetron, and 82% (n = 134) of those who received ondansetron. Adverse events attributed to palonosetron were headache (n = 4), infusion site pain (n = 1), and cardiac issues (n = 5).

Compared to ondansetron, 20 mc/kg palonosetron resulted in significantly greater control of CINV and minimal adverse events in pediatric patients receiving MEC or HEC.