Phase II trials of the serotonin antagonist GR38032F for the control of vomiting caused by cisplatin.

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.