title: Randomized, double-blind trial comparing the antiemetic effect of tropisetron plus metopimazine with tropisetron plus placebo in patients receiving multiple cycles of multiple-day cisplatin-based chemotherapy.
abstract: OBJECTIVE
  To compare the antiemetic efficacy and tolerability of tropisetron plus metopimazine with tropisetron plus placebo during 4 cycles of multiple-day, cisplatin-based chemotherapy.
  
  
  METHODS
  82 chemotherapy-naive patients with germ cell cancer scheduled to 4 cycles of multiple-day cisplatin-based chemotherapy (20 or 40 mg/m(2)/day for 5 days) given every 3 weeks were included. A double-blind parallel trial design was used and patients randomized to tropisetron plus metopimazine or tropisetron plus placebo. Tropisetron was administered as a single 5 mg intravenous dose on days 1-5 and a single 5 mg oral dose on day 6, and metopimazine as 30 mg orally t.i.d. on day 1, and q.i.d on days 2-6.
  
  
  RESULTS
  Patients were evaluable for efficacy during a total of 195 cycles. Small, but certain advantages were obtained with the combination. In cycle 1, complete protection from emetic episodes on day 1, days 1-5, days 6-9 and days 1-9 was achieved in 85.7%, 42.9%, 86.2% and 40.5% with tropisetron plus metopimazine and in 90.0%, 22.5%, 64.3% and 17.5% with tropisetron plus placebo, respectively. This difference achieved statistical significance in the overall period, days 1-9 (P = 0.029). During the entire period (days 1-9), significantly less nausea was seen in patients receiving tropisetron plus metopimazine (P = 0.027), whereas other nausea parameters did not reach statistical significance. The cumulative emetic protection rate after 4 cycles was 0.51 with tropisetron plus metopimazine and 0.25 with tropisetron plus placebo (P = 0.037). Side effects were generally few and mild with both treatments and no significant differences were seen.
  
  
  CONCLUSIONS
  Tropisetron plus metopimazine is superior to tropisetron during 4 cycles of multiple-day cisplatin-based chemotherapy, but both treatments are ineffective in a number of patients. The effect of the combination seems comparable to that of ondansetron plus dexamethasone. Newer drugs such as the neurokinin(1) receptor antagonist, aprepitant, should be investigated to optimize antiemetic therapy in patients receiving multiple-day chemotherapy.
authors.affiliation: Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Copenhagen, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Herrstedt
authors.forename: T C
authors.initials: TC
authors.lastname: Sigsgaard
authors.forename: H A
authors.initials: HA
authors.lastname: Nielsen
authors.forename: J
authors.initials: J
authors.lastname: Handberg
authors.forename: S W
authors.initials: SW
authors.lastname: Langer
authors.forename: S
authors.initials: S
authors.lastname: Ottesen
authors.forename: P
authors.initials: P
authors.lastname: Dombernowsky
mesh_terms: D000293:Adolescent; D000328:Adult; D000932:Antiemetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002945:Cisplatin / Q000009:adverse effects*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D007540:Isonipecotic Acids / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control*; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy*; D000077526:Tropisetron; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D000932:Antiemetics; D000970:Antineoplastic Agents; D007211:Indoles; D007540:Isonipecotic Acids; C005260:metopimazine; D000077526:Tropisetron; D002945:Cisplatin