Phase 2 trial results with the novel neurokinin-1 receptor antagonist casopitant in combination with ondansetron and dexamethasone for the prevention of chemotherapy-induced nausea and vomiting in cancer patients receiving moderately emetogenic chemotherapy.
BACKGROUND
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).


METHODS
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) (>or=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.


RESULTS
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.


CONCLUSIONS
Casopitant plus ond/dex was more effective than ond/dex alone for the prevention of CINV.
Arpornwirat
Wichit
W
Department of Medicine, National Cancer Institute, Bangkok, Thailand.
Albert
Istvan
I
Hansen
Vincent L
VL
Levin
Jeremey
J
Bandekar
Rajesh R
RR
Grunberg
Steven M
SM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000932:Antiemetics / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control*; D064729:Neurokinin-1 Receptor Antagonists; D017294:Ondansetron / Q000008:administration & dosage*; D010879:Piperazines / Q000008:administration & dosage*; D010880:Piperidines / Q000008:administration & dosage*; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*; D014508:Urea
D000932:Antiemetics; D003907:Dexamethasone; D064729:Neurokinin-1 Receptor Antagonists; D017294:Ondansetron; D010879:Piperazines; D010880:Piperidines; C531951:casopitant; D014508:Urea