Reduction of cisplatin-induced emesis by a selective neurokinin-1-receptor antagonist

被引:265
作者
Navari, RM
Reinhardt, RR
Gralla, RJ
Kris, MG
Hesketh, PJ
Khojasteh, A
Kindler, H
Grote, TH
Pendergrass, K
Grunberg, SM
Carides, AD
Gertz, BJ
机构
[1] Merck Res Labs, Clin Pharmacol, Rahway, NJ 07065 USA
[2] Simon Williamson Clin, Birmingham, AL USA
[3] Ochsner Med Ctr, New Orleans, LA USA
[4] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA
[5] St Elizabeths Med Ctr, Boston, MA USA
[6] Capital Comprehens Canc Care Clin, Jefferson City, MO USA
[7] Roswell Pk Canc Inst, Buffalo, NY 14263 USA
[8] Salem Res Grp, Winston Salem, NC USA
[9] Res Med Ctr, Kansas City, MO USA
[10] Fletcher Allen Hlth Ctr, Burlington, VT USA
关键词
D O I
10.1056/NEJM199901213400304
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background The localization of substance P in brain-stem regions associated with vomiting, and the results of studies in ferrets, led us to postulate that a neurokinin-1-receptor antagonist would be an antiemetic in patients receiving anticancer chemotherapy. Methods in a multicenter, double-blind, placebo-controlled trial involving 159 patients who had not previously received cisplatin, we evaluated the prevention of acute emesis (occurring within 24 hours) and delayed emesis (occurring on days 2 to 5) after a single dose of cisplatin therapy (70 mg or more per square meter of body-surface area). Before receiving cisplatin, all the patients received granisetron (10 mu g per kilogram of body weight intravenously) and dexamethasone (20 mg orally). The patients were randomly assigned to one of three treatments in addition to granisetron and dexamethasone: 400 mg of an oral trisubstituted morpholine acetal (also known as L-754,030) before cisplatin and 300 mg on days 2 to 5 (group 1), 400 mg of L-754,030 before cisplatin and placebo on days 2 to 5 (group 2), or placebo before cisplatin and placebo on days 2 to 5 (group 3). Additional medication was available at any time to treat occurrences of vomiting or nausea. Results In the acute-emesis phase, 93 percent of the patients in groups 1 and 2 combined and 67 percent of those in group 3 had no vomiting (P<0.001). In the delayed-emesis phase, 82 percent of the patients in group 1, 78 percent of those in group 2, and 33 percent of those in group 3 had no vomiting (P<0.001 for the comparison between group 1 or 2 and group 3). The median nausea score in the delayed-emesis phase was significantly lower in group 1 than in group 3 (P=0.003). No serious adverse events were attributed to L-754,030. Conclusions The neurokinin-1-receptor antagonist L-754,030 prevents delayed emesis after treatment with cisplatin. Moreover, combining L-754,030 with granisetron plus dexamethasone improves the prevention of acute emesis. (N Engl J Med 1999;340: 190-5.) (C) 1999, Massachusetts Medical Society.
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页码:190 / 195
页数:6
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