A RANDOMIZED, DOUBLE-BLIND COMPARISON OF SINGLE-DOSE AND DIVIDED MULTIPLE-DOSE DOLASETRON FOR CISPLATIN-INDUCED EMESIS

Purpose: Intravenous dolasetron has been shown to be an effective anti emetic agent in patients receiving high-dose cisplatin-containing chem otherapy. Previous studies have suggested that 1.8 mg/kg is an optimal dose for achieving control of emesis and nausea. The objective of thi s study was to compare the efficacy and safety of a single intravenous (IV) dose of dolasetron with an equal divided multiple dose. Methods: In this randomized, double-blind, parallel-group, multicenter study, the efficacy and safety of a single 1.8-mg/kg dose of dolasetron given 30 min prior to high-dose cisplatin (greater than or equal to 80 mg/m (2)) chemotherapy was compared with the same total amount of dolasetro n administered in three separate doses (0.6 mg/kg each) over a 12-h in terval commencing 30 min prior to beginning chemotherapy and ending 11 .5 h later. Antiemetic efficacy, safety, and tolerability were compare d in 55 patients with various malignancies during the 24 h following t he initiation of chemotherapy. The number of emetic episodes was the p rimary efficacy parameter. Results: A single IV dose of dolasetron was generally more effective than a multiple-dose regimen in all measures of efficacy. There was a larger proportion of complete responders in the single-dose group compared with the multiple-dose group (48% vs 23 %), although this difference did not reach statistical significance. C ompared with the multiple-dose group, patients who received a single d ose of dolasetron had a significantly (P = 0.034) longer median time t o the first emetic episode (10.1 h vs > 24 h, respectively). Overall, 53% of patients had either a complete response or a major response to dolasetron, and only 40% of the total patient population received esca pe antiemetic medication in the 24 h after cisplatin administration. E xcept for headache, adverse events were similar with both regimens and were generally of mild or moderate intensity; no serious adverse even ts occurred. Neither dolasetron treatment regimen was associated with any clinically important events, trends in laboratory variables, or di fferences in safety profile. Conclusions: single-dose dolasetron was w ell tolerated and effectively controlled emesis and nausea in patients who received highly emetogenic, high-dose cisplatin chemotherapy. The greater antiemetic efficacy of a single prophylactic dose of dolasetr on offers both convenience and potential cost savings, compared with a multiple-dose schedule of administration.