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

Paul J. Hesketh, Richard J. Gralla, R. T. Webb, W. Ueno, S. DelPrete, M. E. Bachinsky, N. L. Dirlam, C. B. Stack, S. L. Silberman

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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 μg/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.

Original languageEnglish (US)
Pages (from-to)338-343
Number of pages6
JournalJournal of Clinical Oncology
Volume17
Issue number1
StatePublished - Jan 1999
Externally publishedYes

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Neurokinin-1 Receptor Antagonists
Cisplatin
Vomiting
Nausea
Dexamethasone
CJ 11974
Placebos
Granisetron
Receptors, Serotonin, 5-HT3
Double-Blind Method

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Hesketh, P. J., Gralla, R. J., Webb, R. T., Ueno, W., DelPrete, S., Bachinsky, M. E., ... Silberman, S. L. (1999). Randomized phase II study of the neurokinin 1 receptor antagonist CJ- 11,974 in the control of cisplatin-induced emesis. Journal of Clinical Oncology, 17(1), 338-343.

Randomized phase II study of the neurokinin 1 receptor antagonist CJ- 11,974 in the control of cisplatin-induced emesis. / Hesketh, Paul J.; Gralla, Richard J.; Webb, R. T.; Ueno, W.; DelPrete, S.; Bachinsky, M. E.; Dirlam, N. L.; Stack, C. B.; Silberman, S. L.

In: Journal of Clinical Oncology, Vol. 17, No. 1, 01.1999, p. 338-343.

Research output: Contribution to journalArticle

Hesketh, PJ, Gralla, RJ, Webb, RT, Ueno, W, DelPrete, S, Bachinsky, ME, Dirlam, NL, Stack, CB & Silberman, SL 1999, 'Randomized phase II study of the neurokinin 1 receptor antagonist CJ- 11,974 in the control of cisplatin-induced emesis', Journal of Clinical Oncology, vol. 17, no. 1, pp. 338-343.
Hesketh, Paul J. ; Gralla, Richard J. ; Webb, R. T. ; Ueno, W. ; DelPrete, S. ; Bachinsky, M. E. ; Dirlam, N. L. ; Stack, C. B. ; Silberman, S. L. / Randomized phase II study of the neurokinin 1 receptor antagonist CJ- 11,974 in the control of cisplatin-induced emesis. In: Journal of Clinical Oncology. 1999 ; Vol. 17, No. 1. pp. 338-343.
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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 μg/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.",
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T1 - Randomized phase II study of the neurokinin 1 receptor antagonist CJ- 11,974 in the control of cisplatin-induced emesis

AU - Hesketh, Paul J.

AU - Gralla, Richard J.

AU - Webb, R. T.

AU - Ueno, W.

AU - DelPrete, S.

AU - Bachinsky, M. E.

AU - Dirlam, N. L.

AU - Stack, C. B.

AU - Silberman, S. L.

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N2 - 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 μg/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.

AB - 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 μg/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.

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