title: Initial clinical study of tris(2,2-dimethyl-1-aziridinyl)phosphine oxide (TEPA-132).
abstract: Tris(2,2-dimethyl-1-aziridinyl)phosphine oxide (TEPA-132), an alkylating agent, was chosen for clinical trial because of its superior performance in animal tumor systems. This, 2,2-dimethyl derivative of triethylenephosphoramide was also considered to be less toxic than its parent compound. A safe therapeutic dose, 18 mg/kg given intravenously every 2 weeks, was used. At this dose level, mild leukopenia and thrombocytopenia were observed 1 week after the initial dose was given, with complete recovery at 2 weeks. Major toxic effects noted at the 18 mg/kg dose level and greater were leukopenia and thrombocytopenia. Localized venospasm and peripheral vein thrombosis at the infusion site were common. Nausea and vomiting immediately after drug infusion occurred in all patients receiving the therapeutic dose. No other toxic manifestations were noted. One patient with renal cell carcinoma had an objective remission of her disease.
authors.affiliation: General Clinical Research Center, Department of Surgery, Roswell Park Memorial Institute, Buffalo, NY, USA.
authors.forename: A
authors.initials: A
authors.lastname: Mittelman
authors.forename: J
authors.initials: J
authors.lastname: Plager
authors.forename: G P
authors.initials: GP
authors.lastname: Murphy
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001388:Aziridines / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007970:Leukopenia / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D008956:Models, Chemical; D010087:Oxides / Q000627:therapeutic use*; D010720:Phosphines / Q000494:pharmacology / Q000627:therapeutic use*; D012074:Remission Induction; D013921:Thrombocytopenia / Q000188:drug therapy; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001388:Aziridines; D010087:Oxides; D010720:Phosphines; C534653:tris(2,2-dimethyl-1-aziridinyl)phosphine oxide