This randomized, double-blind, dose-ranging, placebo-controlled, phase 2 trial evaluated the neurokinin-1 receptor antagonist casopitant mesylate in combination with ondansetron/dexamethasone (ond/dex) for the prevention of chemotherapy-induced nausea and vomiting (CINV) related to moderately emetogenic chemotherapy (MEC).
Chemotherapy-naive patients who were receiving MEC (N = 723) were randomized to receive either oral placebo or casopitant at doses of 50 mg, 100 mg, or 150 mg daily (on Days 1-3) plus ondansetron (on Days 1-3) and dexamethasone (Day 1). Two exploratory arms evaluated single-dose casopitant (150 mg) plus ond/dex and a 3-day casopitant regimen with once-daily ondansetron and dexamethasone. Primary endpoints were rates of complete response (CR) (no vomiting, retching, rescue therapy, or premature discontinuation) and significant nausea (SN) (≥25 mm on a visual analog scale) over the first 120 hours after Cycle 1 of MEC. Secondary endpoints included acute and delayed CR and SN rates, rates of nausea, vomiting, and safety.
All casopitant doses that were tested significantly increased the proportion of patients with CR: The CR rates were 80.8% with casopitant 50 mg, 78.5% with casopitant 100 mg, and 84.2% with casopitant 150 mg compared with 69.4% in the control group (P = .0127); casopitant 150 mg was identified as the minimally effective dose. In exploratory analyses, single-dose casopitant demonstrated a 79.2% CR rate, and once-daily ondansetron plus casopitant produced an 83.5% CR rate. Vomiting rates in the first 5 days after MEC were reduced with casopitant-containing regimens (from 23% to 10%-16%). Rates of SN did not differ among treatment arms (range, 28%-29%). Casopitant appeared to be well tolerated with no notable differences in overall adverse event frequency.
Casopitant plus ond/dex was more effective than ond/dex alone for the prevention of CINV. Cancer 2009. © 2009 American Cancer Society.