title: Defining the efficacy of neurokinin-1 receptor antagonists in controlling chemotherapy-induced nausea and vomiting in different emetogenic settings-a meta-analysis.
abstract: OBJECTIVE
  This meta-analysis was performed to evaluate the efficacy of neurokinin-1 receptor antagonists (NK1RAs) for the prevention of chemotherapy-induced nausea and vomiting (CINV) across different categories of chemotherapeutic emetogenicity.
  
  
  METHODS
  A systematic review of MEDLINE (via PubMed) and OVID databases, plus major oncology conferences, identified randomized, controlled trials evaluating NK1RAs in combination with a 5-HT3 RA plus a glucocorticoid for management of CINV. Efficacy end points were no emesis, no nausea, and complete response (CR) rates. Data were analyzed using a random effects model.
  
  
  RESULTS
  Twenty-three trials (N = 11,814) were identified. Based on absolute differences (AD) for no emesis (21 %), no nausea (8 %), CR (16 %), and odd ratios (OR) of 2.62, 1.43, and 2.16, respectively, NK1RA regimens provided better CINV protection versus control groups (all p < 0.00001) in patients receiving cisplatin-based highly emetogenic chemotherapy (HEC). In patients receiving anthracycline/cyclophosphamide (AC)-based HEC, respective ADs and ORs were 14, 4, and 11 % and 1.97 (p < 0.0001), 1.17 (p = 0.04), and 1.62 (p < 0.00001). In patients receiving moderately emetogenic chemotherapy (3 trials), no statistically significant benefit of NK1RAs was found; however, positive trends were detected for CR and no emesis. NK1RAs were effective for CINV prevention in a small number of studies using high-dose chemotherapy as conditioning prior to stem cell transplant and cisplatin-based multiple-day chemotherapy (MDC).
  
  
  CONCLUSIONS
  This meta-analysis demonstrated the efficacy of NK1RA in preventing vomiting in patients receiving HEC (including AC), with smaller effects on prevention of nausea. Efficacy is also seen with high-dose chemotherapy and cisplatin-based MDC.
authors.affiliation: Department of Internal Medicine IV, Hematology/Oncology, Martin-Luther- University Halle-Wittenberg, Ernst-Grube-Strasse 40, 06120, Halle, Germany. karin.jordan@uk-halle.de.
authors.forename: Karin
authors.initials: K
authors.lastname: Jordan
authors.affiliation: Princess Margaret Hospital, 610 University Avenue, Toronto, M5G 2M9, Canada.
authors.forename: David G
authors.initials: DG
authors.lastname: Warr
authors.affiliation: WiSP Wissenschaftlicher Service Pharma GmbH, Karl-Benz-Strasse 1, D-40764, Langenfeld, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Hinke
authors.affiliation: Merck & Co., Inc., 2000 Galloping Hill Rd, Kenilworth, NJ, 07033, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Hematology Oncology, Lahey Hospital & Medical Center, 41 Mall Road, Burlington, MA, 01805, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Hesketh
mesh_terms: D000932:Antiemetics / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000145:classification; D006801:Humans; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control; D009369:Neoplasms / Q000188:drug therapy*; D064729:Neurokinin-1 Receptor Antagonists / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control
chemical_list: D000932:Antiemetics; D000970:Antineoplastic Agents; D064729:Neurokinin-1 Receptor Antagonists
keywords: Antiemetics; Chemotherapy-induced nausea and vomiting; Emetogenicity; Neurokinin-1 receptor