title: Comparative safety and effectiveness of serotonin receptor antagonists in patients undergoing chemotherapy: a systematic review and network meta-analysis.
abstract: BACKGROUND
  Although serotonin (5-HT3) receptor antagonists are effective in reducing nausea and vomiting, they may be associated with increased cardiac risk. Our objective was to examine the comparative safety and effectiveness of 5-HT3receptor antagonists (e.g., dolasetron, granisetron, ondansetron, palonosetron, tropisetron) alone or combined with steroids for patients undergoing chemotherapy.
  
  
  METHODS
  We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception until December 2015 for studies comparing 5-HT3receptor antagonists with each other or placebo in chemotherapy patients. The search results were screened, data were abstracted, and risk of bias was appraised by pairs of reviewers, independently. Random-effects meta-analyses and network meta-analyses (NMAs) were conducted.
  
  
  RESULTS
  After screening 9226 citations and 970 full-text articles, we included 299 studies (n = 58,412 patients). None of the included studies reported harms for active treatment versus placebo. For NMAs on the risk of arrhythmia (primary outcome; three randomized controlled trials [RCTs], 627 adults) and mortality (secondary outcome; eight RCTs, 4823 adults), no statistically significant differences were observed between agents. A NMA on the risk of QTc prolongation showed a significantly greater risk for dolasetron + dexamethasone versus ondansetron + dexamethasone (four RCTs, 3358 children and adults, odds ratio 2.94, 95% confidence interval 2.13-4.17). For NMAs on the number of patients without nausea (44 RCTs, 11,664 adults, 12 treatments), number of patients without vomiting (63 RCTs, 15,460 adults, 12 treatments), and number of patients without chemotherapy-induced nausea or vomiting (27 RCTs, 10,924 adults, nine treatments), all agents were significantly superior to placebo. For a NMA on severe vomiting (10 RCTs, 917 adults), all treatments decreased the risk, but only ondansetron and ramosetron were significantly superior to placebo. According to a rank-heat plot with the surface under the cumulative ranking curve results, palonosetron + steroid was ranked the safest and most effective agent overall.
  
  
  CONCLUSIONS
  Most 5-HT3receptor antagonists were relatively safe when compared with each other, yet none of the studies compared active treatment with placebo for harms. However, dolasetron + dexamethasone may prolong the QTc compared to ondansetron + dexamethasone. All agents were effective for reducing risk of nausea, vomiting, and chemotherapy-induced nausea or vomiting.
  
  
  BACKGROUND
  This study was registered at PROSPERO: ( CRD42013003564 ).
authors.affiliation: Knowledge Translation Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, East Building, Room 716, Toronto, Ontario, M5B 1W8, Canada.|Epidemiology Division, Dalla Lana School of Public Health, University of Toronto, 6th Floor, 155 College Street, Toronto, Ontario, M5T 3M7, Canada.
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Tricco
authors.affiliation: Knowledge Translation Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, East Building, Room 716, Toronto, Ontario, M5B 1W8, Canada.|Institute for Health Policy Management & Evaluation, University of Toronto, 4th Floor, 155 College Street, Toronto, Ontario, M5T 3M6, Canada.
authors.forename: Erik
authors.initials: E
authors.lastname: Blondal
authors.affiliation: Knowledge Translation Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, East Building, Room 716, Toronto, Ontario, M5B 1W8, Canada.
authors.forename: Areti Angeliki
authors.initials: AA
authors.lastname: Veroniki
authors.affiliation: Knowledge Translation Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, East Building, Room 716, Toronto, Ontario, M5B 1W8, Canada.|Institute for Health Policy Management & Evaluation, University of Toronto, 4th Floor, 155 College Street, Toronto, Ontario, M5T 3M6, Canada.
authors.forename: Charlene
authors.initials: C
authors.lastname: Soobiah
authors.affiliation: Knowledge Translation Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, East Building, Room 716, Toronto, Ontario, M5B 1W8, Canada.
authors.forename: Afshin
authors.initials: A
authors.lastname: Vafaei
authors.affiliation: Knowledge Translation Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, East Building, Room 716, Toronto, Ontario, M5B 1W8, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Ivory
authors.affiliation: Knowledge Translation Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, East Building, Room 716, Toronto, Ontario, M5B 1W8, Canada.
authors.forename: Lisa
authors.initials: L
authors.lastname: Strifler
authors.affiliation: Knowledge Translation Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, East Building, Room 716, Toronto, Ontario, M5B 1W8, Canada.
authors.forename: Roberta
authors.initials: R
authors.lastname: Cardoso
authors.affiliation: Knowledge Translation Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, East Building, Room 716, Toronto, Ontario, M5B 1W8, Canada.
authors.forename: Emily
authors.initials: E
authors.lastname: Reynen
authors.affiliation: Knowledge Translation Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, East Building, Room 716, Toronto, Ontario, M5B 1W8, Canada.
authors.forename: Vera
authors.initials: V
authors.lastname: Nincic
authors.affiliation: Knowledge Translation Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, East Building, Room 716, Toronto, Ontario, M5B 1W8, Canada.
authors.forename: Huda
authors.initials: H
authors.lastname: Ashoor
authors.affiliation: Knowledge Translation Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, East Building, Room 716, Toronto, Ontario, M5B 1W8, Canada.
authors.forename: Joanne
authors.initials: J
authors.lastname: Ho
authors.affiliation: Knowledge Translation Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, East Building, Room 716, Toronto, Ontario, M5B 1W8, Canada.
authors.forename: Carmen
authors.initials: C
authors.lastname: Ng
authors.affiliation: Knowledge Translation Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, East Building, Room 716, Toronto, Ontario, M5B 1W8, Canada.
authors.forename: Christy
authors.initials: C
authors.lastname: Johnson
authors.affiliation: Knowledge Translation Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, East Building, Room 716, Toronto, Ontario, M5B 1W8, Canada.
authors.forename: Erin
authors.initials: E
authors.lastname: Lillie
authors.affiliation: Knowledge Translation Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, East Building, Room 716, Toronto, Ontario, M5B 1W8, Canada.
authors.forename: Jesmin
authors.initials: J
authors.lastname: Antony
authors.affiliation: Knowledge Translation Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, East Building, Room 716, Toronto, Ontario, M5B 1W8, Canada.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Roberts
authors.affiliation: Departments of Medicine and Community Health Sciences, University of Calgary, TRW Building, 3rd Floor, 3280 Hospital Drive NW, Calgary, Alberta, T2N 4Z6, Canada.
authors.forename: Brenda R
authors.initials: BR
authors.lastname: Hemmelgarn
authors.affiliation: Knowledge Translation Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, East Building, Room 716, Toronto, Ontario, M5B 1W8, Canada. sharon.straus@utoronto.ca.|Department of Geriatric Medicine, University of Toronto, 27 King's College Circle, Toronto, Ontario, M5S 1A1, Canada. sharon.straus@utoronto.ca.
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Straus
mesh_terms: D000328:Adult; D000932:Antiemetics / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D004359:Drug Therapy, Combination; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D009325:Nausea / Q000517:prevention & control; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D014839:Vomiting / Q000517:prevention & control
chemical_list: D000932:Antiemetics; D000970:Antineoplastic Agents; D005938:Glucocorticoids; D058831:Serotonin 5-HT3 Receptor Antagonists
keywords: Chemotherapy; Effectiveness; Network meta-analysis; Safety; Serotonin receptor antagonists; Systematic review