Pharmacokinetics/pharmacodynamics, safety, and tolerability of fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting in pediatric cancer patients.

BACKGROUND: Current antiemetic regimens are less effective in children than in adults. Fosaprepitant was recently approved for prevention of chemotherapy-induced nausea and vomiting (CINV) in children aged six months and older. PROCEDURE: The pharmacokinetic (PK)/pharmacodynamic (PD) profile, safety, and tolerability of a single intravenous dose of fosaprepitant administered concomitantly with ondansetron with/without dexamethasone were evaluated in pediatric patients with cancer receiving emetogenic chemotherapy. PK/PD from three doses of fosaprepitant (3.0, 1.2, and 0.4 mg/kg, up to 150, 60, and 20 mg, respectively) were compared with placebo in 2- to 17-year-old subjects; an open-label amendment evaluated a fourth dose (5.0 mg/kg, up to 150 mg) in those under 12 years old. Historical adult PK data were used for comparison. Efficacy was measured as an exploratory endpoint. RESULTS: PK data were evaluable for 167/234 subjects who completed cycle one. Aprepitant exposures were dose proportional; adolescents (12 to 17 years) receiving fosaprepitant 150 mg had exposures similar to adults at the same dose. Higher weight-normalized doses (5 mg/kg) were necessary for children aged < 12 years to achieve comparable adult exposures. The adverse event profile was typical of cancer patients receiving emetogenic chemotherapy. Drug-related adverse events were reported in 16 (6.8%) subjects, with hiccups being most common (n = 5; 2.1%). CONCLUSIONS: Intravenous fosaprepitant was well tolerated by pediatric subjects with cancer, and dose-proportional exposures were observed. Subjects < 12 years old required higher doses to achieve comparable adult exposures.