title: A phase III, double-blind, randomized trial of palonosetron compared with ondansetron in preventing chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy.
abstract: BACKGROUND
  This pivotal phase III trial evaluated the efficacy and safety of palonosetron in preventing acute and delayed chemotherapy-induced nausea and vomiting (CINV) following highly emetogenic chemotherapy (HEC).
  
  
  METHODS
  Patients were randomized to a single intravenous dose of palonosetron 0.25 mg or 0.75 mg, or ondansetron 32 mg prior to HEC. Dexamethasone pre-treatment (with stratification) was used at investigator discretion. The primary efficacy endpoint was the proportion of patients with complete response (CR) during the first 24 h post-chemotherapy (acute phase).
  
  
  RESULTS
  In the intent-to-treat analysis (n = 667), palonosetron 0.25 mg and 0.75 mg were at least as effective as ondansetron in preventing acute CINV (59.2%, 65.5%, and 57.0% CR rates, respectively); CR rates were slightly higher with palonosetron than ondansetron during the delayed (24-120 h) and overall (0-120 h) phases. Two thirds of patients (n = 447) received concomitant dexamethasone. Patients pre-treated with palonosetron 0.25 mg plus dexamethasone had significantly higher CR rates than those receiving ondansetron plus dexamethasone during the delayed (42.0% versus 28.6%) and overall (40.7% versus 25.2%) phases. Palonosetron and ondansetron were well tolerated.
  
  
  CONCLUSIONS
  Single-dose palonosetron was as effective as ondansetron in preventing acute CINV following HEC, and with dexamethasone pre-treatment, its effectiveness was significantly increased over ondansetron throughout the 5-day post-chemotherapy period.
authors.affiliation: IMO, Clinique de Genolier, Genolier, Vaud, Switzerland.
authors.forename: M S
authors.initials: MS
authors.lastname: Aapro
authors.forename: S M
authors.initials: SM
authors.lastname: Grunberg
authors.forename: G M
authors.initials: GM
authors.lastname: Manikhas
authors.forename: G
authors.initials: G
authors.lastname: Olivares
authors.forename: T
authors.initials: T
authors.lastname: Suarez
authors.forename: S A
authors.initials: SA
authors.lastname: Tjulandin
authors.forename: L F
authors.initials: LF
authors.lastname: Bertoli
authors.forename: F
authors.initials: F
authors.lastname: Yunus
authors.forename: B
authors.initials: B
authors.lastname: Morrica
authors.forename: F
authors.initials: F
authors.lastname: Lordick
authors.forename: A
authors.initials: A
authors.lastname: Macciocchi
mesh_terms: D000328:Adult; D000368:Aged; D000932:Antiemetics / Q000009:adverse effects / Q000627:therapeutic use; D003907:Dexamethasone / Q000009:adverse effects / Q000627:therapeutic use; D004311:Double-Blind Method; D004333:Drug Administration Routes; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control*; D017294:Ondansetron / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077924:Palonosetron; D011812:Quinuclidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D000932:Antiemetics; D007546:Isoquinolines; D011812:Quinuclidines; D017294:Ondansetron; D000077924:Palonosetron; D003907:Dexamethasone