Annals of Oncology Advance Access published online on June 18, 2009
Annals of Oncology, doi:10.1093/annonc/mdp194
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Randomized, double-blind, dose-ranging trial of the oral neurokinin-1 receptor antagonist casopitant mesylate for the prevention of cisplatin-induced nausea and vomiting
1 Division of Medical Oncology , ‘S. Maria’ Hospital, Terni, Italy
2 Centrum Onkologii Instytut, Marii Sklodowskiej-Curie Oddzial w Krakowie, Krakow
3 Oncology Department, Regional Lung Disease Centre, Poznan, Poland
4 Medical Oncology Department, Institute of Oncology Bucharest, Bucharest, Romania
5 GlaxoSmithKline, Collegeville, PA
6 Hematology/Oncology Unit, Fletcher Allen Health Care, Burlington, VT, USA
* Correspondence to: Dr F. Roila, Oncologia Medica, Ospedale S. Maria, Via Tristano di Joannuccio 1, 05100 Terni, Italy. Tel: +39-744-205410; Fax: +39-744-205632; E-mail: roila.fausto{at}libero.it
Background: Casopitant mesylate is a novel, oral neurokinin-1 receptor antagonist with demonstrated antiemetic efficacy. We conducted a randomized, double-blind, controlled phase II trial to evaluate three casopitant doses as part of a triple-therapy regimen for the prevention of nausea and vomiting associated with high-dose cisplatin. The aim of the study was to detect a dose response.
Patients and methods: A total of 493 patients with solid tumors receiving a first cycle of cisplatin 
70 mg/m2 were randomly assigned among six treatment arms. The primary analysis compared a control arm [ondansetron/dexamethasone (Ond/Dex)] with three investigational treatments (Ond/Dex plus oral casopitant 50, 100, or 150 mg administered daily for 3 days). Two exploratory arms were included: one evaluating a single oral casopitant dose of 150 mg added to standard Ond/Dex and another with 3-day oral aprepitant-based therapy (Ond/Dex plus aprepitant 125 mg day 1, 80 mg days 2–3).
Results: The complete response (CR) rate (defined as no vomiting, retching, rescue therapy, or premature discontinuation) was significantly increased in each casopitant arm relative to control over the 120-h evaluation period: 76% (50 mg), 86% (100 mg), 77% (150 mg), and 60% with control (P = 0.0036). The CR rate for the single oral dose regimen was similar to the CR rate reported for the 3-day regimens. No differences were observed in the incidence of nausea or significant nausea among groups in the primary analysis. The most common adverse events related to treatment included headache (n = 10) and hiccups (n = 14).
Conclusion: All doses of oral casopitant as a 3-day regimen (and likely as a 150-mg single oral dose) in combination with Ond/Dex provided significant improvement in the prevention of cisplatin-induced emesis.
antiemetics, antineoplastic combined chemotherapy protocols, combination, drug therapy, nausea, neurokinin-1, vomiting
Received for publication August 28, 2008. Revision received February 25, 2009. Accepted for publication March 6, 2009.