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Japanese Journal of Clinical Oncology 19:216-221 (1989)
© 1989 Foundation for Promotion of Cancer Research

research-article

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

Tetsuro Kubota*, Takao Inada, So Inoue, Masahiko Kuzuoka, Yoshito Arisawa, Akihiko Suto, Susumu Kodaira, Kyuya Ishibiki and Osahiko Abe

Department of Surgery, School of Medicine, Keio University 35 Shinanomachi, Shinjuku-ku, Tokyo 160

*For reprints and all correspondence

Received April 21, 1989; accepted June 23, 1989

The antitumor activity and toxicity of 7-N-(2-((2-({gamma}-L-glutamylaminoethyl) 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 KW21 49 was dose-dependent, and the difference in antitumor effect according to route of administration was minimal. The an titumor spectrum of KW2149 was essentially identical to that of mitomycin C administered in traperiotoneally as a bolus at a dose of 6 mg/kg.

Key Words: KW2149 • Nude mouse • Mitomycin C • Antitumor agent


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