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Title: Comparison of L-758,298, a prodrug for the selective neurokinin-1 antagonist, L-754,030, with ondansetron for the prevention of cisplatin-induced emesis
Authors: Cocquyt, V ×
Van Belie, S
Reinhardt, RR
Decramer, Marc
O'Brien, M
Schellens, JHM
Borms, M
Verbeke, A
Van Aelst, F
De Smet, M
Carides, AD
Eldridge, K
Gertz, BJ #
Issue Date: May-2001
Publisher: Pergamon-elsevier science ltd
Series Title: European journal of cancer vol:37 issue:7 pages:835-842
Abstract: Substance P is localised ill brainstem regions associated with emesis. Based on studies in the ferret, it was postulated that a neurokinin-1 (NK1) receptor antagonist would have antiemetic activity as monotherapy in humans receiving chemotherapy. L-758,298 is a water-soluble, intravenous (i.v.) prodrug for L-754,030, a potent and selective NK1 receptor antagonist. This double-blind, randomised, active-agent (ondansetron)-controlled study enrolled 53 cisplatin-naive patients and evaluated the prevention of both acute (0-24 h) and delayed (days 2-7) emesis after cisplatin treatment (50-100 mg/m(2)). All patients received i.v. L-758,298 (60 or 100 mg) (n=30) or ondansetron (32 mg) (n=23) before cisplatin and efficacy was evaluated up to day 7 post-cisplatin. Nausea was assessed by means of a four-point ordinal scale at intervals over the 7 day period. In the acute period, the proportion of patients without emesis in the L-758,298 and ondansetron groups was 37 and 52%, respectively (no significant difference between the groups), Comparing the distribution of average nausea scores over the entire first 24 h revealed no significant difference between the groups. In the delayed period. the proportion of patients without emesis in the L-758,298 and ondansetron treatment groups was 72 and 30%, respectively (P=0.005), The distribution of average nausea scores in the delayed period was lower in the L-758,298 group compared with the ondansetron group (P=0.15 for the entire delayed period and P=0.043 for day 2 only). No serious adverse events were attributed to L-758,298. A single dose of L-758,298 substantially suppressed the delayed nausea and vomiting characteristic of high dose cisplatin and also appeared to reduce acute emesis post-cisplatin. The data also support the proposition that the underlying mechanism(s) of acute and delayed emesis are different. (C) 2001 Elsevier Science Ltd. All rights reserved.
URI: 
ISSN: 0959-8049
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Pneumology
× corresponding author
# (joint) last author

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