脳腫瘍の化学療法—特に髄腔内投与制癌剤の選択と各種投与法における制癌剤の濃度分布の比較

CHEMOTHERAPY OF BRAIN TUMOR:Studies on Selection of Cytostatic Agents for Intrathecal Administration and Distributions of Cytostatic Agents by Intravenous, Intracarotid and Intrathecal Administrations

I．はじめに

　私どもは数年来脳腫瘍の化学療法，特に制癌剤の髄腔内投与法を中心に研究を行なってきたが^8）9），今回は髄腔内投与法に使用する制癌剤の選択と，髄腔内投与法をはじめ静脈内投与法あるいは頸動脈内投与法を行なつた際の制癌剖の濃度分布の変動について実験動物を用いて検討した。

This paper deals with the experimental studies on the chemotherapy of malignant brain tumor with special reference to the intrathecal administration of cytostatic agents.

The local and systemic changes caused by the intrathecal administration of various cytostatic agents are investigated in animals. As one of the local actions, the destructions of blood brain barrier which can be presumed with measuring the uptake ratio of brain tissue of RISA injected intravenously are studied after the intracisternal administration of cytostatic agents in rabbits. As one of the systemic effects, the changes of body weight after the intrathecal administration of cytostatic agents, are checked in rats. In conclusion of these experiments, the fol-lowing cytostatic agents may be used for the intra-thecal administration: Encloxan (cyclophosphamicle), Methotrexate (amethopterim) and lower doses of Mitomycin C and Tespamin (triethylene thiophos-phoramicle.

In another experiment, the concentrations of Endo-xan (EX) and and Mitomycin C,(MMC) in cerebrospinal fluid (CSF), serum (drawn from femoral vein or right jugural vein) or brain tissue after the intra-venous, right intracarotid or intracisternal administ-rations are investigated in dogs. These results indi-cate that EX is hardly activated in CSF and normal brain tissue. However, the CSF concentration of active metabolite of EX is considerably high for a few hours after the intracisternal administration of EX (10mg/kg) as the result of extremely high concentration of total EX (inactive EX and active metabolite of EX) in CSF. The CSF concentration of MMC by the intracisternal administration of MMC (0.01mg/kg) is maintained more than 1γ/ml for longer than 2 hours. It may be concluded that the intrathecal administrations of EX or lower close of MMC are available for chemotherapy of brain tumor.