title: GR 38032F (GR-C507/75): a novel compound effective in the prevention of acute cisplatin-induced emesis.
abstract: We evaluated, in a multi-center trial, the safety and efficacy of GR 38032F (GR-C507/75), a novel and selective serotonin antagonist, in preventing acute emesis in chemotherapy-naive patients receiving treatment with regimens containing high-dose cisplatin (greater than or equal to 100 mg/m2). Eighty-five patients were randomized to receive GR 38032F, 0.18 mg/kg, either every six or every eight hours for three doses, beginning 30 minutes before cisplatin. Patients were evaluated for emetic episodes (vomiting or retching) over a 24-hour period following cisplatin. All patients were evaluable for toxicity and 83 were evaluable for efficacy. The overall antiemetic response rate was 75% (55% complete response [CR], 20% major response). No difference in antiemetic control between the two administration schedules was noted. Patients with histories of heavy ethanol use had significantly better antiemetic control (74% CR) than modest or non-drinkers (33% CR). Toxicity of GR 38032F was modest and independent of administration schedule. The most common adverse events included mild hepatic transaminase elevations, self-limited diarrhea, dry mouth, headache, and mild sedation. Our data indicate that GR 38032F is a safe and effective agent in the control of acute cisplatin-induced nausea and vomiting. Additional trials exploring dosing, schedule, and comparison to standard antiemetic agents are indicated.
authors.affiliation: Section of Medical Oncology, University Hospital, Boston, MA 02118.
authors.forename: P J
authors.initials: PJ
authors.lastname: Hesketh
authors.forename: W K
authors.initials: WK
authors.lastname: Murphy
authors.forename: E P
authors.initials: EP
authors.lastname: Lester
authors.forename: D R
authors.initials: DR
authors.lastname: Gandara
authors.forename: A
authors.initials: A
authors.lastname: Khojasteh
authors.forename: E
authors.initials: E
authors.lastname: Tapazoglou
authors.forename: G P
authors.initials: GP
authors.lastname: Sartiano
authors.forename: D R
authors.initials: DR
authors.lastname: White
authors.forename: K
authors.initials: K
authors.lastname: Werner
authors.forename: J M
authors.initials: JM
authors.lastname: Chubb
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D002945:Cisplatin / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control*; D017294:Ondansetron; D011897:Random Allocation; D012702:Serotonin Antagonists; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D007093:Imidazoles; D012702:Serotonin Antagonists; D017294:Ondansetron; D002945:Cisplatin