title: Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with moderately emetogenic chemotherapy: results of a randomized, double-blind phase III trial.
abstract: BACKGROUND
  To establish the role of antiemetic therapy with neurokinin-1 (NK1) receptor antagonists (RAs) in nonanthracycline and cyclophosphamide (AC)-based moderately emetogenic chemotherapy (MEC) regimens, this study evaluated single-dose intravenous (i.v.) fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting (CINV) associated with non-AC MEC.
  
  
  METHODS
  In this international, phase III, double-blind trial, adult cancer subjects scheduled to receive ≥1 non-AC MEC on day 1 were randomized to a regimen comprising single-dose i.v. fosaprepitant 150 mg or placebo along with ondansetron and dexamethasone on day 1; control regimen recipients received ondansetron on days 2 and 3. Primary end points were the proportion of subjects achieving a complete response (CR; no vomiting and no use of rescue medication) in the delayed phase (25-120 h after MEC initiation) and safety. Secondary end points included CR in the overall and acute phases (0-120 and 0-24 h after MEC initiation, respectively) and no vomiting in the overall phase. Nausea and the Functional Living Index-Emesis were assessed as exploratory end points.
  
  
  RESULTS
  The fosaprepitant regimen improved CR significantly in the delayed (78.9% versus 68.5%; P < 0.001) and overall (77.1% versus 66.9%; P < 0.001) phases, but not in the acute phase (93.2% versus 91.0%; P = 0.184), versus control. In the overall phase, the proportion of subjects with no vomiting (82.7% versus 72.9%; P < 0.001) and no significant nausea (83.2% versus 77.9%; P = 0.030) was also significantly improved with the fosaprepitant regimen. The fosaprepitant regimen was generally well tolerated.
  
  
  CONCLUSIONS
  Single-dose fosaprepitant added to a 5-HT3 RA and dexamethasone was well tolerated and demonstrated superior control of CINV (primary end point achieved) associated with non-AC MEC. This is the first study to evaluate NK1 RA therapy as an i.v. formulation in a well-defined non-AC MEC population.
  
  
  BACKGROUND
  NCT01594749 (https://clinicaltrials.gov/ct2/show/NCT01594749).
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA cindy.l.weinstein@merck.com.
authors.forename: C
authors.initials: C
authors.lastname: Weinstein
authors.affiliation: Department of Hematology/Oncology, Martin Luther University Halle-Wittenberg, Halle, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Jordan
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Green
authors.affiliation: Department of Hematology and Medical Oncology, Comprehensive Cancer Center at the Desert Regional Medical Center, Palm Springs, CA.
authors.forename: E
authors.initials: E
authors.lastname: Camacho
authors.affiliation: Department of Hematology/Oncology, Reliant Medical Group, Worcester, MA.
authors.forename: S
authors.initials: S
authors.lastname: Khanani
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: E
authors.initials: E
authors.lastname: Beckford-Brathwaite
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: W
authors.initials: W
authors.lastname: Vallejos
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: L W
authors.initials: LW
authors.lastname: Liang
authors.affiliation: Department of Oncology, Weinberg Cancer Institute, Baltimore, MD, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Noga
authors.affiliation: Department of Medical Oncology, Medical Oncology Center of Rosebank, Johannesburg, South Africa.
authors.forename: B L
authors.initials: BL
authors.lastname: Rapoport
mesh_terms: D000932:Antiemetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000627:therapeutic use*; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control*; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D000932:Antiemetics; D000970:Antineoplastic Agents; D009025:Morpholines; C579707:fosaprepitant
keywords: fosaprepitant dimeglumine; moderately emetogenic chemotherapy; nausea; neurokinin-1 receptor antagonists; vomiting