Bleomycin and brain tumors

A logical inference from the recent reports indicating that malignant brain tumors are composed of a heterogeneous cell population is that combination chemotherapy will be required for effective brain tumor control. For several years we have been investigating the use of Bleomycin as an agent to be used in conjunction with radiation therapy and a nitrosourea compound. Since systemically administered Bleomycin does not cross the blood-brain-barrier and has significant toxicity when used parenterally in high doses, we have studied the use of smaller doses of Bleomycin injected directly into the brain tumor cavity. Such an intracerebral dose was more effective in prolonging survival of rats burdened with experimental 9L gliosarcomas than an intravenous dose that is 25 times as great. The combination of intracerebrally administered Bleomycin and radiation therapy was more effective than either modality alone. Furthermore, the combination of Bleomycin delivered intracerebrally and BCNU given systemically was more effective than eitheragent used alone. Finally, in a Phase I clinical trial of Bleomycin given via an Ommaya reservoir to eight patients with recurrent malignant brain tumors, we have demonstrated that individual doses of up to 7.5 units and cumulative doses of up to 255 units can be administered without significant toxicity.