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


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 ( > 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.


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. 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.


CONCLUSIONS
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.
Harman
G S
GS
University of Iowa Hospitals and Clinics, Iowa City 52242, USA.
Omura
G A
GA
Ryan
K
K
Hainsworth
J D
JD
Cramer
M B
MB
Hahne
W F
WF
D000368:Aged; D000932:Antiemetics / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002945:Cisplatin / Q000009:adverse effects*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000188:drug therapy; D016016:Proportional Hazards Models; D011807:Quinolizines / Q000008:administration & dosage*; D012702:Serotonin Antagonists / Q000008:administration & dosage*; D014481:United States; D014839:Vomiting / Q000139:chemically induced / Q000188:drug therapy*
D000932:Antiemetics; D000970:Antineoplastic Agents; D007211:Indoles; D011807:Quinolizines; D012702:Serotonin Antagonists; C060344:dolasetron; D002945:Cisplatin