Medline ® Abstracts for References 19-23
of 'Prevention and treatment of chemotherapy-induced nausea and vomiting in adults'
Comparison of the anti-emetic efficacy of different doses of ondansetron, given as either a continuous infusion or a single intravenous dose, in acute cisplatin-induced emesis. A multicentre, double-blind, randomised, parallel group study. Ondansetron Study Group.
Seynaeve C, Schuller J, Buser K, Porteder H, Van Belle S, Sevelda P, Christmann D, Schmidt M, Kitchener H, Paes D
Br J Cancer. 1992;66(1):192.
A total of 535 chemotherapy naive, hospitalised patients (263 male/272 female) scheduled to receive cisplatin (50-120 mg m-2)-containing regimens participated in a randomised, double-blind, parallel group study to evaluate the efficacy and safety of three intravenous dose schedules of ondansetron in the prophylaxis of acute nausea and emesis. One hundred and eighty two patients received a loading dose of 8 mg of ondansetron followed by a 24 h infusion of 1 mg h-1 (group 1); 180 and 173 patients received single doses of 32 mg (group II) and 8 mg (group III) respectively, followed by a 24 h placebo infusion. Complete and major control (less than or equal to 2 emetic episodes) of acute emesis was achieved in 74% of patients in group I, 78% in group II and 74% in group III. Seventy seven per cent of the patients in group I, and 75% of patients in groups II and III respectively experienced no or mild nausea during the 24 h observation period. A retrospective stratification of the efficacy data on the basis of patient gender showed the response rate in females to be significant lower (43% vs 67%; less than 0.001). Ondanestron was well tolerated; mild headache was the most commonly reported adverse event (11% of patients) with a similar incidence in the three groups of patients. In conclusion, a single intravenous dose of 8 mg of ondansetron given prior to chemotherapy is as effective as a 32 mg daily dose given as either a single dose of a continuous infusion in the prophylaxis of acute cisplatin-induced emesis.
Rotterdam Cancer Institute/Dr Daniel den Hoed Kliniek, The Netherlands.
Stratified, randomized, double-blind comparison of intravenous ondansetron administered as a multiple-dose regimen versus two single-dose regimens in the prevention of cisplatin-induced nausea and vomiting.
Beck TM, Hesketh PJ, Madajewicz S, Navari RM, Pendergrass K, Lester EP, Kish JA, Murphy WK, Hainsworth JD, Gandara DR
J Clin Oncol. 1992;10(12):1969.
PURPOSE: This study compares the efficacy and safety of two single-dose regimens with the approved three-dose regimen of ondansetron in the prevention of cisplatin-induced emesis.
PATIENTS AND METHODS: This multicenter study was a stratified, randomized, double-blind, and parallel group design. Chemotherapy-naive inpatients were randomized to receive intravenous (IV) ondansetron (Zofran; Glaxo Inc, Research Triangle Park, NC) 0.15 mg/kg times three doses, every 4 hours or a single 8-mg or 32-mg dose followed by two saline doses that began 30 minutes before cisplatin administration. Cisplatin (high-dose>or = 100 mg/m2 or medium-dose 50 to 70 mg/m2) was given as a single infusion (<or = 3 hours). Patients were monitored for emetic episodes, adverse events, and laboratory safety parameters for 24 hours after cisplatin administration.
RESULTS: A total of 699 patients (359 high-dose, 340 medium-dose) were enrolled. Of these, 618 were assessable for efficacy (15 ineligible, 66 protocol deviations). The 32-mg dose was superior to the 8-mg single dose with regard to total number of emetic episodes (high-dose, P = .015; medium-dose, P<.001), complete response (no emetic episodes: high-dose, 48% v 35%; P = .048; medium-dose, 73% v 50%; P = .001) and failure rate (>5 emetic episodes, withdrawn or rescued: high-dose, 20% v 34%; P = .018; medium-dose, 9% v 23%; P = .005). The 32-mg single dose was also superior to the 0.15 mg/kg times three dose regimen with regard to total number of emetic episodes (medium-dose, P = .033) and failure rate (high-dose, 20% v 36%; P = .009; medium-dose, 9% v 22%; P = .011). Ondansetron was well tolerated. The most common adverse event was headache. An approximate 10-fold increase in the incidence of clinically significant transaminase elevations was observed in the high-dose versus medium-dose cisplatin strata (aspartate aminotransferase [AST], 6.5% v 0.7%; serum alanine aminotransferase [ALT], 5.0% v 0.3%).
CONCLUSION: A 32-mg single dose of ondansetron is more effective than a single 8-mg dose and is at least as effective as the standard regimen of 0.15 mg/kg times three doses in the prevention of cisplatin-induced acute emesis.
Mountain States Tumor Institute, Boise, ID 82712-6297.
A double-blind comparison of the efficacy of two dose regimens of oral granisetron in preventing acute emesis in patients receiving moderately emetogenic chemotherapy.
Ettinger DS, Eisenberg PD, Fitts D, Friedman C, Wilson-Lynch K, Yocom K
BACKGROUND: The purpose of this study was to define an optimal administration schedule of granisetron for patients receiving moderately emetogenic chemotherapy by comparing the antiemetic efficacy and safety of 2 mg of the drug administrated orally.
METHODS: In this double-blind, randomized, parallel study, 2-dose regimens of oral granisetron were evaluated in 697 adult cancer patients. Patients were stratified by gender and randomized to receive 2 mg oral granisetron, either as a divided dose given 1 hour prior to chemotherapy and 12 hours after the start of chemotherapy, or as a single dose 1 hour prior to chemotherapy at Cycle 1. The primary efficacy endpoints assessed were the percentage of patients with complete response (no nausea, no emesis, and no additional antiemetic medication during the 24-hour post-chemotherapy interval) and the incidence of emesis and nausea. Following completion of Cycle 1, patients were given the opportunity to receive open-label granisetron (2 mg once daily) on the first day of each remaining cycle of chemotherapy.
RESULTS: No statistically significant differences in any of the endpoints were observed between the two treatment groups. Approximately 50% of patients in both treatment groups achieved complete response. The proportion of patients with no episodes of emesis occurred with similar frequency in the two treatment groups. Approximately 52% of patients in either treatment group were free of nausea during the postchemotherapy period. There was no difference between treatment groups regarding the use of antiemetic rescue medication. Finally, the incidence of adverse experiences was similar for both treatment groups.
CONCLUSIONS: Both dose regimens of oral granisetron were similarly effective in controlling nausea and vomiting in the 24-hour interval following chemotherapy. Granisetron was well tolerated with few adverse events attributable to the study drug.
The Johns Hopkins Oncology Center, Baltimore, Maryland 21287, USA.
A randomized, double-blind comparison of single-dose and divided multiple-dose dolasetron for cisplatin-induced emesis.
Harman GS, Omura GA, Ryan K, Hainsworth JD, Cramer MB, Hahne WF
Cancer Chemother Pharmacol. 1996;38(4):323.
PURPOSE: 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 effectivethan 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.
University of Iowa Hospitals and Clinics, Iowa City 52242, USA.
Effect of schedule and maintenance on the antiemetic efficacy of ondansetron combined with dexamethasone in acute and delayed nausea and emesis in patients receiving moderately emetogenic chemotherapy: a phase III trial by the National Cancer Institute of Canada Clinical Trials Group.
Kaizer L, Warr D, Hoskins P, Latreille J, Lofters W, Yau J, Palmer M, Zee B, Levy M, Pater J
J Clin Oncol. 1994;12(5):1050.
PURPOSE: This study examines whether the schedule of ondansetron significantly influences its antiemetic efficacy in the first 24 hours after chemotherapy, whether the administration of oral ondansetron after 24 hours is effective in preventing delayed emesis, and whether the efficacy of ondansetron is preserved over multiple courses of moderately emetogenic chemotherapy.
PATIENTS AND METHODS: A multicenter double-blind study randomized 302 cancer patients to one of three treatment arms. Arm A received dexamethasone 10 mg intravenously (i.v.) plus ondansetron (Zofran; Glaxo Canada Inc, Toronto, Canada) 8 mg i.v. prechemotherapy plus ondansetron 8 mg orally every 12 hours postchemotherapy for nine doses. Arm B received dexamethasone 10 mg i.v. plus ondansetron 16 mg i.v. prechemotherapy plus placebo orally postchemotherapy in the same schedule as arm A. Arm C received dexamethasone 10 mg i.v. plus ondansetron 8 mg prechemotherapy plus ondansetron 8 mg orally postchemotherapy for one dose followed by placebo orally every 12 hours for eight more doses. Response was assessed by the number of reported episodes of vomiting and by severity of nausea measured on a visual analog scale (VAS).
RESULTS: The two schedules of ondansetron used in the first 24 hours were no different in their antiemetic efficacy, with similar rates for complete responses (76.7% v 72.0%, P = .472), complete plus major responses (90.2% v 82.0%, P = .135), and severity of nausea (P = .348). Oral ondansetron after 24 hours was more effective than placebo in preventing delayed nausea and emesis, with superior rates of complete responses (59.6% v 42.1%, P = .012 by one-sided test), complete plus major responses (80.9% v 66.3%, P = .018 by one-sided test), and less severe nausea (9.2 mm v 18.6 mm on a 100-mm VAS, P = .002). The efficacy of ondansetron was maintained over subsequent courses of chemotherapy.
CONCLUSION: The schedule of ondansetron in the first 24 hours does not influence its efficacy. The use of oral maintenance ondansetron is effective in preventing delayed maintenance ondansetron is effective in preventing delayed nausea and emesis after moderately emetogenic chemotherapy.
Department of Medicine, Credit Valley Hospital, Mississauga; Ontario, Canada.