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Experimental Antitumor Activity against Murine Tumor Model Systems of 8-Carbamoyl-3-(2-chloroethyl)imidazo[5,1-d]-1,2,3,5-tetrazin-4(3H)-one (Mitozolomide), a Novel Broad-Spectrum Agent

par Hickman, John J.A.;Stevens, Malcolm F G;Gibson, Neil N.W.;Langdon, Simon S.P.;Fizames, Christian;Lavelle, François;Atassi, Ghanem ;Lunt, Edward;Tilson, Robert R.M.
Référence Cancer research, 45, 7, page (3008-3013)
Publication Publié, 1985-07

Article révisé par les pairs

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Résumé :

carbamoyl-3-(2-chloroethyl)imidazo[5,1 -d]-1,2,3,5-tetrazin-4(3H)-one (mitozolomicle) demonstrates curative action against a range of murine tumor model systems. At single doses of between 20 and 40 mg/kg, the latter of which approximates the 10% lethal dose value in mice, the compound elicited cures against the L1210 and P388 leukemias irrespective of the route of tumor and/or drug administration; in these tests, animals receiving 105 cells i.p. survived >60 days after treatment. Potent effects were also observed against the TLX5 lymphoma (s.c.) and B16 melanoma (i.p.). In other experiments, 7 of 10 animals implanted with 2 x 105 Lewis lung carcinoma cells survived >60 days while 10 of 10 animals survived >60 days after implantation of the Colon 26 tumor. Potent inhibition of the solid tumor models was also observed with complete cures of the Colon 38, M5076 sarcoma, and ADJ/PC6A plasmacytoma. In cross-resistance studies, the compound was ineffective against an L1210 leukemia made resistant to 1,3-bis(2-chloroethyl)-1 -nitrosourea and against a TLX5 lymphoma resistant to dimethyltriazenes but cured animals bearing the L1210 leukemia with derived resistance to cyclophosphamide. © 1985, American Association for Cancer Research. All rights reserved.