Randomized phase II study of the neurokinin 1 receptor antagonist CJ-11,974 in the control of cisplatin-induced emesis - PubMed (original) (raw)
Clinical Trial
Randomized phase II study of the neurokinin 1 receptor antagonist CJ-11,974 in the control of cisplatin-induced emesis
P J Hesketh et al. J Clin Oncol. 1999 Jan.
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.
Comment in
- Use of placebos in delayed-emesis studies.
Navari RM. Navari RM. J Clin Oncol. 1999 May;17(5):1648-50. J Clin Oncol. 1999. PMID: 10334561 No abstract available. - Studies on new antiemetic drugs.
Roila F, Tonato M, Ballatori E, Del Favero A. Roila F, et al. J Clin Oncol. 1999 Jun;17(6):1960-2. doi: 10.1200/jco.1999.17.6.1960. J Clin Oncol. 1999. PMID: 10561240 No abstract available.
Similar articles
- Reduction of cisplatin-induced emesis by a selective neurokinin-1-receptor antagonist. L-754,030 Antiemetic Trials Group.
Navari RM, Reinhardt RR, Gralla RJ, Kris MG, Hesketh PJ, Khojasteh A, Kindler H, Grote TH, Pendergrass K, Grunberg SM, Carides AD, Gertz BJ. Navari RM, et al. N Engl J Med. 1999 Jan 21;340(3):190-5. doi: 10.1056/NEJM199901213400304. N Engl J Med. 1999. PMID: 9917226 Clinical Trial. - Prevention of cisplatin-induced acute and delayed emesis by the selective neurokinin-1 antagonists, L-758,298 and MK-869.
Van Belle S, Lichinitser MR, Navari RM, Garin AM, Decramer ML, Riviere A, Thant M, Brestan E, Bui B, Eldridge K, De Smet M, Michiels N, Reinhardt RR, Carides AD, Evans JK, Gertz BJ. Van Belle S, et al. Cancer. 2002 Jun 1;94(11):3032-41. doi: 10.1002/cncr.10516. Cancer. 2002. PMID: 12115394 Clinical Trial. - Prevention of cisplatin-induced emesis by the oral neurokinin-1 antagonist, MK-869, in combination with granisetron and dexamethasone or with dexamethasone alone.
Campos D, Pereira JR, Reinhardt RR, Carracedo C, Poli S, Vogel C, Martinez-Cedillo J, Erazo A, Wittreich J, Eriksson LO, Carides AD, Gertz BJ. Campos D, et al. J Clin Oncol. 2001 Mar 15;19(6):1759-67. doi: 10.1200/JCO.2001.19.6.1759. J Clin Oncol. 2001. PMID: 11251007 Clinical Trial. - Management of cisplatin-induced delayed emesis.
Hesketh P. Hesketh P. Oncology. 1996 Jun;53 Suppl 1:73-7. doi: 10.1159/000227644. Oncology. 1996. PMID: 8692555 Review.
Cited by
- Consensus proposals for the prevention of acute and delayed vomiting and nausea following high-emetic-risk chemotherapy.
Kris MG, Hesketh PJ, Herrstedt J, Rittenberg C, Einhorn LH, Grunberg S, Koeller J, Olver I, Borjeson S, Ballatori E. Kris MG, et al. Support Care Cancer. 2005 Feb;13(2):85-96. doi: 10.1007/s00520-004-0699-x. Epub 2004 Nov 23. Support Care Cancer. 2005. PMID: 15565277 Review. - Potential of substance P antagonists as antiemetics.
Diemunsch P, Grélot L. Diemunsch P, et al. Drugs. 2000 Sep;60(3):533-46. doi: 10.2165/00003495-200060030-00002. Drugs. 2000. PMID: 11030465 Review. - A multinational study to measure the value that patients with cancer place on improved emesis control following cisplatin chemotherapy.
Dranitsaris G, Leung P, Ciotti R, Ortega A, Spinthouri M, Liaropoulos L, Labianca R, Quadri A. Dranitsaris G, et al. Pharmacoeconomics. 2001;19(9):955-67. doi: 10.2165/00019053-200119090-00007. Pharmacoeconomics. 2001. PMID: 11700782 - Defining the efficacy of neurokinin-1 receptor antagonists in controlling chemotherapy-induced nausea and vomiting in different emetogenic settings-a meta-analysis.
Jordan K, Warr DG, Hinke A, Sun L, Hesketh PJ. Jordan K, et al. Support Care Cancer. 2016 May;24(5):1941-1954. doi: 10.1007/s00520-015-2990-4. Epub 2015 Oct 17. Support Care Cancer. 2016. PMID: 26476625 - The neurokinin 1 receptor antagonist, ezlopitant, reduces appetitive responding for sucrose and ethanol.
Steensland P, Simms JA, Nielsen CK, Holgate J, Bito-Onon JJ, Bartlett SE. Steensland P, et al. PLoS One. 2010 Sep 1;5(9):e12527. doi: 10.1371/journal.pone.0012527. PLoS One. 2010. PMID: 20824145 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical