Single-dose ondansetron for the prevention of cisplatin-induced emesis: efficacy results

Ondansetron 0.15 mg/kg, given intravenously (IV) every 4 hours for three doses, has replaced metoclopramide as standard antiemetic therapy for patients receiving cisplatin-based chemotherapy. Several clinical observations suggested that ondansetron may be effective when given in a single dose: (1) demonstration of efficacy over a wide dose range, (2) similar efficacy with dosing intervals of 2, 4, 6, and 8 hours, and (3) efficacy of single-dose regimens with high-dose metoclopramide and other 5-hydroxytryptamine3 antagonists. In this study, patients receiving cisplatin-based chemotherapy were randomized to receive one of three ondansetron dosing regimens: ondansetron 0.15 mg/kg IV every 4 hours x 3 (standard schedule), ondansetron 32 mg IV x 1, or ondansetron 8 mg IV x 1. All patients were chemotherapy naive, at least 18 years of age, Karnofsky performance status > or = 60%, and inpatients. The number of emetic episodes, nausea, and food intake were measured during the 24 hours following cisplatin administration. Six hundred eighteen evaluable patients were randomized to the three ondansetron treatment groups; 301 received moderate-dose cisplatin (50 to 70 mg/m2) and 317 received high-dose cisplatin (> or = 100 mg/m2). Patients in both cisplatin groups receiving ondansetron 32 mg had a higher complete response rate, lower failure rate, fewer total emetic episodes, less nausea, and more food intake than did patients receiving ondansetron 8 mg. In addition, the 32-mg schedule was superior to the standard three-dose schedule in that it had a lower failure rate and higher food intake and was equivalent to the standard regimen in all other comparisons. All three schedules were well tolerated. Ondansetron 32 mg given prior to cisplatin is superior to a single 8-mg dose and is at least as effective, if not superior to, the standard three-dose schedule (0.15 mg/kg every 4 hours). On the basis of these data, ondansetron 32 mg should be considered standard therapy in patients receiving cisplatin-based chemotherapy and should be the schedule with which new antiemetics and alternate dosing schedules are compared.