title: A double-blind, randomised comparison of the anti-emetic efficacy of two intravenous doses of dolasetron mesilate and granisetron in patients receiving high dose cisplatin chemotherapy.
abstract: This multicentre, double-blind, double-dummy, randomised trial was designed to compare the efficacy and safety of single intravenous doses of dolasetron mesilate and granisetron in the prevention of acute emesis and nausea due to high-dose (> or = 80 mg/m2) cisplatin. Single intravenous doses of 1.8 or 2.4 mg/kg of dolasetron mesilate or 3 mg of granisetron hydrochloride were administered in a volume of 50 ml over a 5-min period, beginning 30 min prior to cisplatin (> or = 80 mg/m2) administration. The number and timing of emetic episodes, time to administration of escape anti-emetic medication, severity of nausea by visual analogue scale (VAS), and safety were monitored for 24 h after the start of cisplatin-containing chemotherapy. Investigators' evaluations of overall efficacy and patients' satisfaction with therapy were recorded at the end of the 24-h study period. Of the 474 patients evaluable for efficacy, complete responses were achieved by 54, 47 and 48% of patients given dolasetron mesilate 1.8 mg/kg, dolasetron mesilate 2.4 mg/kg and granisetron, respectively. Statistically, treatment groups had comparable complete and complete plus major responses, times to first emesis, and use of escape medication; patient maximum nausea severity and treatment satisfaction ratings; and physician nausea severity and overall efficacy assessments. For the majority of efficacy endpoints, 1.8 mg/kg dolasetron mesilate produced numerically superior responses compared with the 2.4 mg/kg dose. Gender and prior chemotherapy were significant predictors of complete response; males and chemotherapy-naive patients had higher responses. The overall incidences of adverse events were comparable among the treatment groups; headache and diarrhoea were most common. In conclusion, 1.8 and 2.4 mg/kg of dolasetron mesilate and granisetron (3 mg) were equally effective in preventing nausea and vomiting induced by highly emetogenic cisplatin-containing chemotherapy. In addition, because no additional benefit was observed with 2.4 mg/kg of dolasetron mesilate and numerically greater responses were observed with the 1.8 mg/kg dose, the lower dose of 1.8 mg/kg is optimal for further clinical development.
authors.affiliation: Hôpital Louis Pasteur, Colmar, France.
authors.forename: B
authors.initials: B
authors.lastname: Audhuy
authors.forename: P
authors.initials: P
authors.lastname: Cappelaere
authors.forename: M
authors.initials: M
authors.lastname: Martin
authors.forename: A
authors.initials: A
authors.lastname: Cervantes
authors.forename: M
authors.initials: M
authors.lastname: Fabbro
authors.forename: A
authors.initials: A
authors.lastname: Rivière
authors.forename: D
authors.initials: D
authors.lastname: Khayat
authors.forename: H
authors.initials: H
authors.lastname: Bleiberg
authors.forename: M
authors.initials: M
authors.lastname: Faraldi
authors.forename: N
authors.initials: N
authors.lastname: Claverie
authors.forename: E
authors.initials: E
authors.lastname: Aranda
authors.forename: G
authors.initials: G
authors.lastname: Auclerc
authors.forename: B
authors.initials: B
authors.lastname: Audhuy
authors.forename: A
authors.initials: A
authors.lastname: Benhammouda
authors.forename: H
authors.initials: H
authors.lastname: Bleiberg
authors.forename: L
authors.initials: L
authors.lastname: Cals
authors.forename: P
authors.initials: P
authors.lastname: Cappelaere
authors.forename: A
authors.initials: A
authors.lastname: Cattan
authors.forename: A
authors.initials: A
authors.lastname: Cervantes
authors.forename: B
authors.initials: B
authors.lastname: Chevallier
authors.forename: T
authors.initials: T
authors.lastname: Conroy
authors.forename: D
authors.initials: D
authors.lastname: Cupissol
authors.forename: J
authors.initials: J
authors.lastname: De Grève
authors.forename: E
authors.initials: E
authors.lastname: Diaz-Rubio
authors.forename: J F
authors.initials: JF
authors.lastname: Seitz
mesh_terms: D000328:Adult; D000368:Aged; D000932:Antiemetics / Q000008:administration & dosage* / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002945:Cisplatin / Q000009:adverse effects*; D004311:Double-Blind Method; D005260:Female; D017829:Granisetron / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control*; D011807:Quinolizines / Q000008:administration & dosage* / Q000009:adverse effects; D012702:Serotonin Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D000932:Antiemetics; D000970:Antineoplastic Agents; D002945:Cisplatin; D017829:Granisetron; D007211:Indoles; D011807:Quinolizines; D012702:Serotonin Antagonists; C060344:dolasetron