A randomized, double-blind comparison of single-dose and divided multiple-dose dolasetron for cisplatin-induced emesis

• Published in: Cancer chemotherapy and pharmacology 1996, Vol.38 (4), p.323-328
• Main Authors: HARMAN, G. S, OMURA, G. A, RYAN, K, HAINSWORTH, J. D, CRAMER, M. R, HAHNE, W. F
• Format: Article
• Language: English
• Subjects: Aged; Antiemetics - administration & dosage; Antineoplastic Agents - adverse effects; Biological and medical sciences; Cisplatin - adverse effects; Double-Blind Method; Drug Administration Schedule; Drug toxicity and drugs side effects treatment; Female; Humans; Indoles - administration & dosage; Male; Medical sciences; Middle Aged; Nausea - chemically induced; Nausea - drug therapy; Pharmacology. Drug treatments; Proportional Hazards Models; Quinolizines - administration & dosage; Serotonin Antagonists - administration & dosage; Toxicity: digestive system; United States; Vomiting - chemically induced; Vomiting - drug therapy
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s002800050490

Intravenous dolasetron has been shown to be an effective antiemetic agent in patients receiving high-dose cisplatin-containing chemotherapy. Previous studies have suggested that 1.8 mg/kg is an optimal dose for achieving control of emesis and nausea. The objective of this study was to compare the efficacy and safety of a single intravenous (IV) dose of dolasetron with an equal divided multiple dose. 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 ( > or = 80 mg/m2) chemotherapy was compared with the same total amount of dolasetron administered in three separate doses (0.6 mg/kg each) over a 12-h interval commencing 30 min prior to beginning chemotherapy and ending 11.5 h later. Antiemetic efficacy, safety, and tolerability were compared in 55 patients with various malignancies during the 24 h following the initiation of chemotherapy. The number of emetic episodes was the primary efficacy parameter. 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. Compared with the multiple-dose group, patients who received a single dose of dolasetron had a significantly (P = 0.034) longer median time to 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 escape antiemetic medication in the 24 h after cisplatin administration. Except for headache, adverse events were similar with both regimens and were generally of mild or moderate intensity; no serious adverse events occurred. Neither dolasetron treatment regimen was associated with any clinically important events, trends in laboratory variables, or differences in safety profile. single-dose dolasetron was well 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 dolasetron offers both convenience and potential cost savings, compared with a multiple-dose schedule of administration.