title: Phase II trials of the serotonin antagonist GR38032F for the control of vomiting caused by cisplatin.
abstract: Three phase II studies of the serotonin antagonist GR38032F were conducted. In trial 1, 20 patients given initial chemotherapy with cisplatin at doses greater than or equal to 100 mg/m2 were randomized to receive three GR38032F doses (0.18 mg/kg) on an every-2-hour or every-4-hour schedule. In trial 2, eight similar patients were given three 0.04-mg/kg doses every 2 hours. In trial 3, 12 previously treated patients receiving cisplatin at 20-25 mg/m2 on 4 or 5 consecutive days each received three daily GR38032F doses (0.15 mg/kg) every 2 hours. In trial 1, 35% of the patients had no emesis [95% confidence interval (CI), 16%-58%] and 55% had one or two emetic episodes (95% CI, 32%-76%). Results were similar between the every-2-hour and every-4-hour schedules. In trial 2, only one of eight patients (13%) had no vomiting (95% CI, 1%-50%). In trial 3, in which previously treated patients were studied, complete control ranged from 75% on day 1 to 33% on day 3. Mild sedation, headache, and transient elevations of serum SGOT (AST) were observed. No extrapyramidal symptoms occurred. A dose of 0.15-0.18 mg/kg every 2 hours for three iv doses is recommended. Further comparison and combination studies of GR38032F are warranted.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
authors.forename: M G
authors.initials: MG
authors.lastname: Kris
authors.forename: R J
authors.initials: RJ
authors.lastname: Gralla
authors.forename: R A
authors.initials: RA
authors.lastname: Clark
authors.forename: L B
authors.initials: LB
authors.lastname: Tyson
mesh_terms: D000328:Adult; D000368:Aged; D002945:Cisplatin / Q000009:adverse effects*; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D017294:Ondansetron; D012702:Serotonin Antagonists; D014839:Vomiting / Q000517:prevention & control*
chemical_list: D007093:Imidazoles; D012702:Serotonin Antagonists; D017294:Ondansetron; D002945:Cisplatin