STUDY OF EFFECTIVENESS OF BLEOMYCIN IN RAT-BRAIN TUMOR-MODEL INTRAVENOUSLY AND INTRA-CEREBRALLY

Bleomycin (BLM) is an antitumor antibiotic produced by Streptomyces verticillus. It has special affinity for ectodermal tissues. Since gliomas are of ectodermal origin, the therapeutic value of this drug was evaluated in the 9L gliosarcoma model in inbred Fisher rats. The drug normally does not cross the blood brain barrier (BBB), but in brain tumors the permeability of the BBB is altered and drug can be detected in brain tumor tissue. This study compared the efficacy of bleomycin given intracerebrally in tumor bearing animals and to the effectiveness of the intravenous route. Using a weekly schedule of drug administration the optimal dose was 0.5 mg/kg intracerebrally (p<0.01). Survival following treatment by this route was significantly better (p<0.01) than for intravenous BLM or control therapy. The LD 50 for this route of administration was determined to be 3.0 mg/kg. Animals treated intravenously at 1.5 or 2.5 mg/kg did not show any improved survival compared to controls. It was clear that the intracerebral route was superior to the intravenous route. © 1979.