Single-dose intravenous casopitant in combination with ondansetron and dexamethasone for the prevention of oxaliplatin-induced nausea and vomiting: a multicenter, randomized, double-blind, active-controlled, two arm, parallel group study

Purpose

The primary objective was to determine if a single dose of casopitant 90?mg added to ondansetron and dexamethasone would improve the control of chemotherapy-induced nausea and vomiting (CINV) over 0–120?h following initiation of oxaliplatin-based moderately emetic chemotherapy (MEC) compared to ondansetron and dexamethasone alone.

Methods

Patients with colorectal cancer received either casopitant or placebo intravenously (IV) added to ondansetron 8?mg bid oral on study days?1 to 3 and one dose of dexamethasone 8?mg IV given prior to starting the oxaliplatin on day?1. The primary endpoint was the percentage of subjects achieving complete response (CR; no vomiting/retching or use of rescue medication) during 120?h after initiation of chemotherapy in cycle 1.

Results

No difference in the rate of CR was noted in the casopitant group compared to the placebo group for the overall (placebo 85%, casopitant 86%, p?=?0.7273), acute (placebo 96%, casopitant 97%), or delayed phases (placebo 85%, casopitant 86%). The average area under curve (0–∞) of casopitant after a single 90-mg IV dose was 8,390?ng?h/mL. At 24?h after casopitant 90-mg IV dosing, the plasma casopitant concentration was 24% lower than the values noted in prior studies with 150?mg oral administration, and the plasma exposure of the major metabolite (GSK525060) was 18% lower.

Conclusions

Addition of single-dose casopitant 90?mg IV did not improve the control of CINV at any time during 120?h following initiation of oxaliplatin-based MEC. Excellent control of CINV was achieved in this study population with the combination of ondansetron and dexamethasone alone.