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.
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.
Kubota
T
T
Department of Surgery, School of Medicine, Keio University, Tokyo.
Inada
T
T
Inoue
S
S
Kuzuoka
M
M
Arisawa
Y
Y
Suto
A
A
Kodaira
S
S
Ishibiki
K
K
Abe
O
O
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000231:Adenocarcinoma, Papillary / Q000188:drug therapy / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000188:drug therapy / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016685:Mitomycin; D008937:Mitomycins / Q000008:administration & dosage / Q000627:therapeutic use*; D009368:Neoplasm Transplantation; D011897:Random Allocation; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents; D008937:Mitomycins; C057625:KW 2149; D016685:Mitomycin