title: Evaluation of p-F-Phe-m-bis-(2-chloroethyl)amino-L-Phe-Met-ethoxy HCl against transplantable and spontaneous murine neoplasia.
abstract: The therapeutic efficacy of PTT.119, p-F-Phe-m-bis-(2-chloroethyl)amino-L-Phe-Met-ethoxy HCl, was evaluated using the transplantable L1210 leukemia and Ridgway osteogenic sarcoma tumor lines and the spontaneous C3H/StRos mammary tumor and AKR leukemia tumor models. Given in a single i.p. dose at 5-10 mg/kg on day 2 or in two injections of 5-7 mg each on days 2 and 9 to BDf1 mice with peritoneal L1210 leukemia grafts, PTT.119 increased the life spans (ILS) of the population dying of tumor by 94%-313%. In addition, 10% of the mice receiving 7 mg PTT.119 on days 2 and 9 were free of L1210 leukemic grafts when autopsied at the end of the 70-day observation period. The average life span of AKR mice with Ridgway osteogenic sarcoma grafts was significantly increased from 36-40 days to greater than 79 days following one or two s.c. injections of 5, 7, or 12.5 mg/kg PTT.119. Administration of PTT.119 at 14 or 14 and 21 days after tumor graft not only induced regression of palpable tumors but resulted in the absence of grafts in 60%-70% of the mice in several of the treated groups on autopsy at 180 days. In contrast, spontaneous mammary tumors were less susceptible to PTT.119; an ILS of only 15%-38% was observed in C3H/StRos mice, which eventually succumbed to tumor. Nevertheless, the total regression of initial tumors and the absence of further tumor incidence (greater than 180 days) was confirmed by autopsy in 5%-10% of the C3H/StRos mice receiving multiple i.p. injections of 5 or 7.5 mg/kg PTT.119. The drug was highly effective against spontaneous AKR leukemia; multiple s.c. or i.p. injections for a total of 15-40 mg/kg PTT.119 increased the average 25-day life span up to 723% and sustained remission in 9%-40% of the animals for greater than 6 months.
authors.affiliation: Department of Neoplastic Diseases, Mount Sinai School of Medicine, City University of New York, NY 10029.
authors.forename: M J
authors.initials: MJ
authors.lastname: Yagi
authors.forename: J G
authors.initials: JG
authors.lastname: Bekesi
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D007938:Leukemia / Q000188:drug therapy* / Q000401:mortality; D007939:Leukemia L1210 / Q000188:drug therapy* / Q000401:mortality; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy* / Q000401:mortality; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D009588:Nitrogen Mustard Compounds / Q000627:therapeutic use*; D012516:Osteosarcoma / Q000188:drug therapy* / Q000401:mortality; D012074:Remission Induction
chemical_list: D000970:Antineoplastic Agents; D009588:Nitrogen Mustard Compounds; C038259:ambamustine