脳腫瘍の化学療法—Bleomycinの効果

CHEMOTHERAPY OF BRAIN TUMORS: EFFECT OF BLEOMYCIN

　そもそも脳腫瘍の治療の原則は外科的手術であり，僅かに放射線療法が補助的に応用されてきた程度である。しかし膠芽腫や転移性腫瘍など，いわゆる悪性脳腫瘍では今なお手術的に根治せしめることが困難な場合が少なくない。そのため化学療法や免疫療法などの内科的治療にも興味がもたれるようになつてきた。

　制癌剤としてアルキル化剤が登場して間もなく，脳腫瘍に対してもこれらが全身的に投与されたが，主として血液像に対する著しい副作用のために，肝心の脳腫瘍に対する効果はほとんどみとめられなかつた^11）。その後はもつぱら局所的化学療法が開発され，アルキル化剤の脳灌流法による投与や^13）25），代謝拮抗剤の持続的頸動脈内注入法^3）17）による投与などが試みられてきた。その結果全身的投与法の際にみられるような著しい副作用は一応避けることができ，しかも放射線療法にほぼ匹敵できるような効果も得られるようになつた。ことに著者らの試みた経皮的挿管留置法による5-FUの接続的頸動脈内注入法^17）は手技も簡単であり，脳腫瘍の化学療法としては広く応用されるものと考えていた。

Bleomycin has been used chiefly by the intra-venous route, for the treatment of various types of brain tumors since January 1969, with such excel-lent results that had never been attained with the chemotherapeutic agents heretofore introduced.

One hundred and eight patients of brain tumors have hitherto been treated with Bleomycin. The therapy is still under way or has already been dis-continued in 35 of these cases, and has, therefore, been completed in the other 73 cases. Those patientswere comprised of 50 cases of glioma, 12 cases ofprimary or metastatic carcinoma, four cases ofmeningioma or meningosarcoma, and seven casesof mescellaneous tumors.

In the glioma group Bleomycin therapy may besaid to have been effective in about 50% of thepatients treated to date. Thirty-three of 50 patientsof glioma are still alive to-day and seven caseswith marked effects are included among them. Nodistinct, given tendency has been revealed to existin the possible difference in the effectiveness ofBleomycin due to the type of glioma, but it appearsthat the effective cases are less among the patientsof glioblastoma. The longest survivor is an intra-ventricular ependymoma. About 34 months passedafter the first craniotomy and 30 months passedafter the completion of the Bleomycin therapy.

When the concentration of Bleomycin in thetumor tissue was measured by bioassay, it was foundat a level of 0.3 γ/ml in the encysted fluid and O.9 γ/mg in the tumor tissue in only one case ofastrocytoma, grade 3 out of the 10 cases of glioma.In this particular case, nearly the same concentra-tion was detected in the encysted fluid examinedone year ago. Bleomycin was also detected in thecystic fluid of each one of granuloma and congenitalsubarachnoidal cyst.

As for the histological regression after the Bleo-mycin therapy, tendency of fibrosis of tumor, es-pecially in the perivascular area was commonlyseen.

According to our experiences heretofore obtained,complete recovery from such the malignant braintumors can hardly be expected by Bleomycin therapyalone. Therefore, mode of administration of theagent, combination of adjuvant therapies other tfianBleomycin therapy, simple but reliable method ofscreening for Bleomycin therapy etc. should bestudied further.