title: 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.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Hematology and Oncology, Lahey Clinic Medical Center, Burlington, MA 01805, USA. Paul.Hesketh@Lahey.org
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Hesketh
authors.forename: Oliver
authors.initials: O
authors.lastname: Wright
authors.forename: Gerardo
authors.initials: G
authors.lastname: Rosati
authors.forename: Mark
authors.initials: M
authors.lastname: Russo
authors.forename: Jeremey
authors.initials: J
authors.lastname: Levin
authors.forename: Stephen
authors.initials: S
authors.lastname: Lane
authors.forename: Vladimir
authors.initials: V
authors.lastname: Moiseyenko
authors.forename: Pierre
authors.initials: P
authors.lastname: Dube
authors.forename: Mikhail
authors.initials: M
authors.lastname: Kopp
authors.forename: Anatoly
authors.initials: A
authors.lastname: Makhson
mesh_terms: D000368:Aged; D000932:Antiemetics / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D019540:Area Under Curve; D015179:Colorectal Neoplasms / Q000188:drug therapy; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control; D017294:Ondansetron / Q000008:administration & dosage / Q000627:therapeutic use*; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010879:Piperazines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010880:Piperidines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control; D014508:Urea
chemical_list: D000932:Antiemetics; D003907:Dexamethasone; D017294:Ondansetron; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D010879:Piperazines; D010880:Piperidines; C558658:GSK 525060; C531951:casopitant; D014508:Urea