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

Cancer. 2009 Dec 15;115(24):5807-16. doi: 10.1002/cncr.24630.

Abstract

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.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antiemetics / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Dexamethasone / administration & dosage*
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nausea / chemically induced
  • Nausea / prevention & control*
  • Neurokinin-1 Receptor Antagonists*
  • Ondansetron / administration & dosage*
  • Piperazines / administration & dosage*
  • Piperidines / administration & dosage*
  • Vomiting / chemically induced
  • Vomiting / prevention & control*

Substances

  • Antiemetics
  • Neurokinin-1 Receptor Antagonists
  • Piperazines
  • Piperidines
  • casopitant
  • Ondansetron
  • Dexamethasone