Phase II Trials of the Serotonin Antagonist GR38032F for the Control of Vomiting Caused by Cisplatin

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Abstract
Three phase II studies of the serotonin antagonist GR38032F were conducted. In trial 1, 20 patients given initial chemotherapy with cisplatin at doses >=100 mg/m 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/m 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. [J Natl Cancer Inst 1989;81:42–46]