[Animal experiments for intratumoral chemotherapy with bleomycin (author's transl)]

Abstract

The intense clinical interest in bleomycin as an anti-tumour agent has led to different methods of administration in an attempt to administer sufficiently high concentrations of the drug to the tumor. Therefore, a study was designed to determine the distribution and the therapeutic effect of a bleomycin emulsion and aqueous bleomycin after different routes of application. The tissue distribution of radioactively labelled bleomycin emulsion and aqueous bleomycin was determined in tumor-free CF 1 and tumor-bearing (EL 4, L 1210) C 57 Bl 6 and DBA 2 mice after local (s.c., i.t.) and systemic (i.v.) injection. The distribution studies for aqueous 57Co-bleomycin showed increased activity in the injection sites and the lymph nodes draining the injection sites after s.c. and i.t. injection compared to i.v. administration of the drug. In comparison to the aqueous local administration, the application of 57Co-bleomycin emulsion resulted in a disproportional increase of the 57Co-bleomycin concentration at the injection sites and in the draining lymph nodes. To prove the therapeutic relevance of the bleomycin tissue distribution tumor-bearing (line 10) strain 2 guinea pigs were treated with different modes of bleomycin. Animals with already lymphogenously metastasized tumors have been cured by means of low i.t. doses of the bleomycin emulsion. Guinea pigs treated with i.t. administration of aqueous bleomycin need, compared to the bleomycin emulsion, five times higher doses for tumor-free survival. Intravenously treated animals died either because of progressive tumor growth or because of toxic bleomycin effects. These findings made by animal experiments favor the i.t. treatment of head and neck carcinomas with a bleomycin emulsion.