title: Dose-ranging evaluation of the serotonin antagonist dolasetron mesylate in patients receiving high-dose cisplatin.
abstract: OBJECTIVE
  This dose-ranging trial of intravenous dolasetron mesylate (MDL73,147EF) was performed to determine its adverse and antiemetic effects in patients receiving cisplatin at doses > or = 100 mg/m2.
  
  
  METHODS
  Eighty-nine patients treated with initial cisplatin received a single intravenous dose of dolasetron mesylate administered over 20 minutes beginning 30 minutes before chemotherapy. The following four dose levels were studied: 1.8, 2.4, 3.0, and 5.0 mg/kg. Emesis and adverse effects were measured for 24 hours after cisplatin.
  
  
  RESULTS
  All adverse effects were mild and transient including loose stools, headache, serum AST/ALT elevations, and asymptomatic prolongation of ECG intervals. Among the dose levels, no-emesis rates from 24% to 52% were observed, and the percentage of patients having zero, one, or two emetic episodes ranged from 48% to 82%. Complete control of vomiting increased as the dose was escalated to 2.4 mg/kg, but did not improve further with higher doses.
  
  
  CONCLUSIONS
  Dolasetron mesylate can be administered safely at doses up to 5.0 mg/kg, with comparable complete protection rates and increased adverse effects at doses greater than 2.4 mg/kg. Antiemetic activity was seen after cisplatin. Trials comparing single infusions of dolasetron mesylate and ondansetron are under way.
authors.affiliation: Thoracic Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
authors.forename: M G
authors.initials: MG
authors.lastname: Kris
authors.forename: S M
authors.initials: SM
authors.lastname: Grunberg
authors.forename: R J
authors.initials: RJ
authors.lastname: Gralla
authors.forename: L
authors.initials: L
authors.lastname: Baltzer
authors.forename: S A
authors.initials: SA
authors.lastname: Zaretsky
authors.forename: D
authors.initials: D
authors.lastname: Lifsey
authors.forename: L B
authors.initials: LB
authors.lastname: Tyson
authors.forename: L
authors.initials: L
authors.lastname: Schmidt
authors.forename: W F
authors.initials: WF
authors.lastname: Hahne
mesh_terms: D000328:Adult; D000368:Aged; D000932:Antiemetics / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control; D011807:Quinolizines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control
chemical_list: D000932:Antiemetics; D007211:Indoles; D011807:Quinolizines; D012702:Serotonin Antagonists; C060344:dolasetron; D002945:Cisplatin