Randomized phase II study of the neurokinin 1 receptor antagonist CJ-11,974 in the control of cisplatin-induced emesis

Purpose: to determine the efficacy and safety of the neurokinin type 1 rece ptor antagonist CJ-11,974 for the control of high-dose cisplatin-induced em esis, Patients and Methods: A double-blind, randomized, phase II design with a gr oup sequential stopping rule was used in this study. Sixty-one patients wit h cancer who were receiving cisplatin at a dose of at least 100 mg/m(2) for the first time were enrolled. All patients received granisetron 10 mu g/kg and dexamethasone 20 mg intravenously 30 minutes before they were given ci splatin. Patients were randomly assigned to two groups: group 1 received CJ -11,974 100 mg, and group 2 received placebo orally 30 minutes before and 1 2 hours after cisplatin and then twice daily on days 2 through 5 after cisp latin. The primary end paint was the percentage of patients who developed d elayed emesis (emesis on the second to fifth days after cisplatin). Results: thirty patients were enrolled in group 1, and 31 patients were enr olled in group 2, Fifty-eight patients were assessable for efficacy. Comple te control of emesis (expressed as the percentage of patients who had no em esis) war as follows: day 1,85.7% (group I) and 66.7% (group 2) (P = .090); days 2 through 5, 67.8% (group 1) and 36.6% (group 2) (P = .0425, adjusted ): days 1 through 5, 64.3% (group 1) and 30% (group 2) (P = .009). Patients in group 1 experienced significantly less nausea than patients in group 2 on day 1 (P = .024). Treatment was well tolerated in both groups. Conclusion: We conclude from this exploratory phase II trial that CJ-11,974 is superior to placebo in controlling cisplatin-induced delayed emesis and may provide additive benefit in acute emesis and nausea control when combi ned with a 5-hydroxytryptamine-3 receptor antagonist and dexamethasone. Add itional larger trials are indicated to confirm the clinical value of CJ-11, 974. J Clin Oncol 17:338-343, (C) 1999 by American Society of Clinical Oncology.