title: Early clinical trial of MDL 73.147 EF: a new 5-HT3-receptors antagonist for the prevention of chemotherapy-induced nausea and vomiting.
abstract: BACKGROUND
  Like MDL 72.222, one of the first selective 5-hydroxytryptamine3 (5-HT3) receptors antagonist discovered, MDL 73.147 EF has been shown to possess antiemetic properties in the ferret model. We conducted a phase I study with MDL 73.147 EF in 31 patients, treated with emetogenic drugs over one to five days (cisplatin, cyclophosphamide, doxorubicin, dacarbazine).
  
  
  METHODS
  5 groups of at least 5 patients received rising unit doses of MDL 73.147 EF (10 to 50 mg) intravenously before chemotherapy, with two more doses per day if needed. Nausea was assessed by a patient-completed visual analogue scale and episodes of vomiting recorded by an independent observer.
  
  
  RESULTS
  51.6% of the patients were complete responders on day one and 40% on days two to five. One patient was given other rescue antiemetic therapy. Adverse events included constipation (25.8%), mildly elevated blood pressure (12.9%) and other minor events. No extrapyramidal effects have been reported. There was no suggestion of dose-dependent efficacy at the dose levels studied in this limited set of patients.
  
  
  CONCLUSIONS
  We conclude that MDL 73.147 EF is a well tolerated and possibly effective antiemetic.
authors.affiliation: Division of Onco-Hematology, Cantonal University Hospital, Geneva, Switzerland.
authors.forename: V
authors.initials: V
authors.lastname: Kirchner
authors.forename: M
authors.initials: M
authors.lastname: Aapro
authors.forename: P
authors.initials: P
authors.lastname: Alberto
authors.forename: P
authors.initials: P
authors.lastname: O'Grady
authors.forename: B
authors.initials: B
authors.lastname: Busch
authors.forename: M
authors.initials: M
authors.lastname: Boyce
mesh_terms: D000293:Adolescent; D000328:Adult; D000932:Antiemetics / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D003248:Constipation / Q000139:chemically induced; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control*; D009369:Neoplasms / Q000188:drug therapy*; 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