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

Abstract

PURPOSE:

To determine the efficacy and safety of the neurokinin type 1 receptor antagonist CJ-11,974 for the control of high-dose cisplatin-induced emesis.

PATIENTS AND METHODS:

A double-blind, randomized, phase II design with a group sequential stopping rule was used in this study. Sixty-one patients with cancer who were receiving cisplatin at a dose of at least 100 mg/m2 for the first time were enrolled. All patients received granisetron 10 microg/kg and dexamethasone 20 mg intravenously 30 minutes before they were given cisplatin. 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 12 hours after cisplatin and then twice daily on days 2 through 5 after cisplatin. The primary end point was the percentage of patients who developed delayed emesis (emesis on the second to fifth days after cisplatin).

RESULTS:

Thirty patients were enrolled in group 1, and 31 patients were enrolled in group 2. Fifty-eight patients were assessable for efficacy. Complete control of emesis (expressed as the percentage of patients who had no emesis) was as follows: day 1, 85.7% (group 1) 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 combined with a 5-hydroxytryptamine-3 receptor antagonist and dexamethasone. Additional larger trials are indicated to confirm the clinical value of CJ-11,974.

• Authors: P J Hesketh, R J Gralla, R T Webb, W Ueno, S DelPrete, M E Bachinsky, N L Dirlam, C B Stack, S L Silberman
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 17 Issue 1 Pg. 338-43 (Jan 1999) ISSN: 0732-183X [Print] United States
• PMID: 10458252 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antiemetics
• Antineoplastic Agents
• Benzene Derivatives
• CJ 11974
• Neurokinin-1 Receptor Antagonists
• Dexamethasone
• Cisplatin
• Granisetron

Topics

• Adult
• Aged
• Antiemetics (adverse effects, therapeutic use)
• Antineoplastic Agents (adverse effects)
• Benzene Derivatives (adverse effects, therapeutic use)
• Cisplatin (adverse effects)
• Dexamethasone (therapeutic use)
• Double-Blind Method
• Female
• Granisetron (therapeutic use)
• Humans
• Male
• Middle Aged
• Neurokinin-1 Receptor Antagonists
• Vomiting (chemically induced, drug therapy, prevention & control)