title: A multicentre, double-blind study comparing placebo, ondansetron and ondansetron plus dexamethasone for the control of cisplatin-induced delayed emesis. Ondansetron Delayed Emesis Study Group.
abstract: BACKGROUND
  The purpose of this study was to investigate the efficacy and safety of oral ondansetron, given alone or in combination with dexamethasone in the control of cisplatin-induced delayed emesis.
  
  
  METHODS
  This was an international, multicentre, double-blind, randomised, placebo-controlled, parallel group study. A total of 640 chemotherapy-naïve patients received ondansetron 8 mg i.v. and dexamethasone 20 mg i.v. for the control of acute emesis prior to cisplatin (> or = 70 mg/m2) on day 1. Patients who were not rescued or withdrawn on day 1 were to be randomised 24 hours after the start of cisplatin administration to one of four groups; group I placebo oral (p.o.), twice daily (bd) on days 2-6 (n = 125); group II ondansetron (8 mg p.o. bd) on days 2/3 followed by placebo (p.o. bd) on days 4-6 (n = 199); group III ondansetron (8 mg p.o. bd) on days 2-6 (n = 214); group IV ondansetron (8 mg p.o. bd) plus dexamethasone (4 mg p.o. bd) on days 2-6 (n = 66).
  
  
  RESULTS
  On day 1, 81% of patients had complete control of acute emesis, with 68% having no emesis and no nausea. Over days 2/3 and over days 2-6, significantly more patients receiving ondansetron plus dexamethasone (group IV) reported no emesis and no nausea (49% and 45%, respectively) compared to ondansetron alone (32% and 27%, respectively) or placebo (group I; 33% and 27%, respectively; P < 0.05 for all pairwise comparisons). There were no significant differences in the control of emesis over days 2/3, where 61% of patients had complete emetic control (0 emetic episodes) with ondansetron plus dexamethasone (group IV), 54% with ondansetron (groups II + III) and 49% with placebo (group I). In the distribution of nausea grades, ondansetron plus dexamethasone (group IV) was significantly superior to ondansetron (groups II + III); P = 0.037) and placebo (group I; P = 0.013) over days 2/3. Over days 2-6 there were no significant differences in the control of emesis, however a comparison of the distribution of nausea grades over days 2-6 showed ondansetron plus dexamethasone (group IV) to be significantly superior to ondansetron (group III; P = 0.043) and placebo (group I; P = 0.024). All treatments were well tolerated and no unexpected drug-related adverse events were reported. There were no differences in the overall incidence of adverse events between the active treatment groups or placebo. Constipation and headache, recognised side effects of 5-HT3 receptor antagonists, were the most commonly reported adverse events with the incidence of constipation with ondansetron alone (group III) being significantly greater than with over days 2-6 (14% vs. 6%; P = 0.030).
  
  
  CONCLUSIONS
  In contrast to some previous investigations, in this study, ondansetron alone appears to have a minor role in the control of cisplatin-induced delayed emesis and nausea. In conclusion, the combination of oral ondansetron plus dexamethasone is superior to ondansetron and to placebo.
authors.affiliation: Royal Adelaide Hospital, Australia.
authors.forename: I
authors.initials: I
authors.lastname: Olver
authors.forename: W
authors.initials: W
authors.lastname: Paska
authors.forename: A
authors.initials: A
authors.lastname: Depierre
authors.forename: J F
authors.initials: JF
authors.lastname: Seitz
authors.forename: D J
authors.initials: DJ
authors.lastname: Stewart
authors.forename: L
authors.initials: L
authors.lastname: Goedhals
authors.forename: B
authors.initials: B
authors.lastname: McQuade
authors.forename: J
authors.initials: J
authors.lastname: McRae
authors.forename: J R
authors.initials: JR
authors.lastname: Wilkinson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000932:Antiemetics / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002945:Cisplatin / Q000009:adverse effects* / Q000627:therapeutic use; D003907:Dexamethasone / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced* / Q000517:prevention & control*; D009369:Neoplasms / Q000188:drug therapy; D017294:Ondansetron / Q000009:adverse effects / Q000627:therapeutic use*; D010919:Placebos; D013997:Time Factors; D014839:Vomiting / Q000139:chemically induced* / Q000517:prevention & control*
chemical_list: D000932:Antiemetics; D000970:Antineoplastic Agents; D010919:Placebos; D017294:Ondansetron; D003907:Dexamethasone; D002945:Cisplatin