Antitumor activity of 7-N-(2-((2-(gamma-L-glutamylamino) ethyl) dithio) ethyl) mitomycin C (KW2149) against human tumor xenografts serially transplanted into nude mice

Jpn J Clin Oncol. 1989 Sep;19(3):216-21.

Abstract

The antitumor activity and toxicity of 7-N-(2-((2-(gamma-L-glutamylamino) ethyl) dithio) ethyl) mitomycin C (KW2149) were evaluated using a human tumor xenograft--nude mouse system, and compared with those of the maternal compound, mitomycin C. The maximum tolerated dose of KW2149 was estimated to be 15 mg/kg by bolus intraperitoneal or intravenous injection, at which a remarkable reduction of spleen weight was observed, suggesting bone marrow suppression by this agent. A bolus injection of KW2149 seemed to be more effective than a divided injection schedule, when a total of 15 mg KW2149/kg was administered to mice bearing breast (MX-1) and colon (Co-4) carcinomas. The antitumor activity of KW2149 was dose-dependent, and the difference in antitumor effect according to route of administration was minimal. The antitumor spectrum of KW2149 was essentially identical to that of mitomycin C administered intraperiotoneally as a bolus at a dose of 6 mg/kg.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / pathology
  • Adenocarcinoma, Papillary / drug therapy
  • Adenocarcinoma, Papillary / pathology
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma / drug therapy*
  • Carcinoma / pathology
  • Carcinoma, Intraductal, Noninfiltrating / drug therapy
  • Carcinoma, Intraductal, Noninfiltrating / pathology
  • Dose-Response Relationship, Drug
  • Humans
  • Injections, Intraperitoneal
  • Injections, Intravenous
  • Male
  • Mice
  • Mice, Inbred A
  • Mice, Inbred BALB C
  • Mice, Nude
  • Mitomycin
  • Mitomycins / administration & dosage
  • Mitomycins / therapeutic use*
  • Neoplasm Transplantation
  • Random Allocation
  • Transplantation, Heterologous

Substances

  • Antineoplastic Agents
  • Mitomycins
  • KW 2149
  • Mitomycin