title: Dose-ranging evaluation of the serotonin antagonist GR-C507/75 (GR38032F) when used as an antiemetic in patients receiving anticancer chemotherapy.
abstract: GR-C507/75 (GR38032F) antagonizes the 5-HT3 (serotonin) receptor and prevents cisplatin-induced emesis in animals. In this dose-ranging trial, 44 patients with cancer receiving chemotherapy known to produce nausea and vomiting (including cisplatin, cyclophosphamide, and doxorubicin) received three intravenous (IV) infusions of GR-C507/75 every two hours beginning 30 minutes before chemotherapy. Ten dosage levels were explored, ranging from 0.04 mg/kg to 0.35 mg/kg in each of the three infusions. Toxicities were mild and included sedation, dizziness, headache, transient elevations of SGOT or alanine aminotransferase (ALT), and dry mouth. No akathisia or acute dystonic reactions were observed. Antiemetic effects were seen in patients receiving cisplatin at 120 mg/m2. GR-C507/75 can be safely administered on this schedule at IV dosages up to 0.35 mg/kg in patients receiving chemotherapy. Further studies of this agent at higher dosages and by different schedules are appropriate.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
authors.forename: M G
authors.initials: MG
authors.lastname: Kris
authors.forename: R J
authors.initials: RJ
authors.lastname: Gralla
authors.forename: R A
authors.initials: RA
authors.lastname: Clark
authors.forename: L B
authors.initials: LB
authors.lastname: Tyson
mesh_terms: D000328:Adult; D000368:Aged; D000932:Antiemetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D017294:Ondansetron; D011985:Receptors, Serotonin / Q000187:drug effects
chemical_list: D000932:Antiemetics; D000970:Antineoplastic Agents; D007093:Imidazoles; D011985:Receptors, Serotonin; D017294:Ondansetron