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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.
AuthorsM J Yagi, J G Bekesi
JournalCancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 26 Issue 3 Pg. 215-20 ( 1990) ISSN: 0344-5704 [Print] Germany
PMID2357770 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antineoplastic Agents
  • Nitrogen Mustard Compounds
  • ambamustine
Topics
  • Adenocarcinoma (drug therapy, mortality)
  • Animals
  • Antineoplastic Agents (therapeutic use)
  • Drug Screening Assays, Antitumor
  • Female
  • Leukemia (drug therapy, mortality)
  • Leukemia L1210 (drug therapy, mortality)
  • Mammary Neoplasms, Animal (drug therapy, mortality)
  • Mice
  • Mice, Inbred Strains
  • Neoplasm Transplantation
  • Nitrogen Mustard Compounds (therapeutic use)
  • Osteosarcoma (drug therapy, mortality)
  • Remission Induction

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