Multicenter, Randomized, Double-Blind, Ondansetron (Ond)-Controlled, Dose-Ranging, Parallel Group Trial Of The Neurokinin-1 Receptor Antagonist (Nk-1 Ra) Casopitant Mesylate For Chemotherapy-Induced Nausea/Vomiting (Cinv) In Patients (Pts) Receiving Moderately Emetogenic Chemotherapy (Mec).

8512 Background: Casopitant mesylate is a potent, selective, oral NK-1 RA, which has shown activity in preventing CINV in preclinical studies. Based on phase I positron emission tomography (PET) studies, casopitant doses from 50–150 mg result in 70–95% saturation of NK-1 receptors. This phase II trial evaluated the addition of casopitant to standard prophylaxis (ond + dexamethasone [dex]) in pts receiving MEC. Methods: MEC regimens included ≥ 1 of the following (in mg/m2): cyclophosphamide (ctx) 500–1,500 with other MEC; ctx alone 750–1,500; oxaliplatin ≥ 85; doxorubicin ≥ 60; epirubicin ≥ 90; or carboplatin AUC ≥ 5. Pts were stratified by gender and taxane use. Pts in the first 5 arms received ond 8 mg BID days (D) 1–3 + dex 8 mg IV D1 with either placebo, casopitant 50 mg QD D1–3, casopitant 100 mg QD D1–3, casopitant 150 mg QD D1–3, or casopitant 150 mg D1. Arm 6 received a different ond regimen (16 mg QD D1–3) + dex 8 mg IV D1 + casopitant 150 mg QD D1–3. Primary endpoints were rates of complete response (CR [no vomiting, retching, rescue meds or premature withdrawal]) and no significant nausea (SN, assessed by visual analogue scale) during the first 120 h after initiation of MEC. Arms 5/6 were exploratory and not included in primary analysis. Planned enrollment was 118 pts/arm for intent-to-treat (ITT) analysis. Results: ITT group includes 719 pts (60% male, 40% female). CR rate (120h) was 70% with ond control; 81% for casopitant 50mg; 79% for 100mg; and 85% for 150mg (p=.012, Cochran-Armitage trend test). CR rates (24h) and no SN (120h) were similar among all groups. CR and no SN rates in the exploratory arms were 80% and 66%, respectively, in arm 5 and 84% and 70% in arm 6. Adverse events were similar across all arms, with nausea, fatigue, and neutropenia (≤ 24%) as most common. All casopitant doses were generally well tolerated. Conclusions: Casopitant demonstrated activity in control of CINV at all doses, with the 1-day dose of particular interest, when added to a standard ond + dex regimen in both male and female pts receiving a variety of MEC regimens. [Table: see text]