Randomized phase II trial of the neurokinin-1 receptor antagonist (NK-1 RA) casopitant mesylate with ondansetron (ond)/dexamethasone (dex) for chemotherapy-induced nausea/vomiting (CINV) in patients (pts) receiving highly emetogenic chemotherapy (HEC)

Abstract

8513 Background: A combination of a 5-HT3 receptor antagonist (5-HT3 RA) + dex is standard for prevention of CINV due to HEC. However, NK-1 RAs are now also of interest. The current trial evaluated casopitant mesylate, a potent, oral, selective NK-1 RA, in a triple therapy regimen with a 5-HT3 RA and dex in pts receiving HEC. Methods: In this multicenter, randomized, double-blind, placebo-controlled, dose-ranging, parallel group study, pts receiving HEC were stratified by gender and randomized among six arms. HEC consisted of regimens including cisplatin ≥ 70 mg/m2 IV over 1–4 hours (h) day 1 (D1). All pts received ond 32mg IV D1 and dex PO D1–4 with either placebo control, casopitant 50mg QD D1–3, casopitant 100mg QD D1–3, or casopitant 150mg QD D1–3. Pts on exploratory arms received ond/dex plus either casopitant 150 mg D1 only or aprepitant 125mg D1 and 80mg D2–3. The primary endpoint was complete response (CR) rate (no vomiting, retching, rescue medications or premature withdrawals) during the first 120 h following initiation of HEC. Target intent-to-treat (ITT) group enrollment was 82 pts per arm. Results: 493 enrolled patients comprised the ITT group. CR rate was 60% in the control arm; 76% for casopitant 50mg; 86% for 100mg; and 77% for 150mg (p=.0036, Cochran-Armitage trend test). CR rate was 75% with casopitant 150 mg D1 and 72% for 3-day aprepitant. CR rates at 24 h were similar in all groups (86%-96%). Casopitant prolonged time to emesis (p=.0029) and increased the proportion of pts without vomiting (p=.0122) relative to control. There were no differences in rates of nausea or use of rescue medication among groups. Adverse events were similar across all arms, with neutropenia, nausea, and hiccups (≤ 17%) as most common. All casopitant doses were generally well tolerated. Conclusions: The addition of casopitant to ond/dex at all doses tested and in 1- or 3-day administration regimens was well tolerated and significantly reduced CINV rates over a 5-day period in pts receiving HEC. The results of the exploratory 1-day regimen are of particular interest for future evaluation. [Table: see text]