Neurological Surgery 脳神経外科36巻2号

2008年02月発行

連載 悪性脳腫瘍治療の今とこれから

2．転換期を迎えた脳腫瘍の化学療法

著者： 吉野篤緒¹ 片山容一¹

所属機関： ¹日本大学医学部脳神経外科学系神経外科学分野

ページ範囲：P.173 - P.183

Ⅰ．はじめに

　脳腫瘍のなかで化学療法の適応となるものは，悪性神経膠腫（malignant glioma），悪性リンパ腫，胚細胞性腫瘍が主なものである（Table 1）．そのなかでも本稿では，頭蓋内腫瘍のうち約30％を占めるとされる神経膠腫に対する化学療法について，変遷を踏まえて最近の知見を概説する．

　神経膠腫は，組織学的に星細胞系腫瘍（astrocytic tumors），乏突起膠細胞系腫瘍（oligodendroglial tumors），上衣細胞系腫瘍，脈絡叢腫瘍，混合膠腫，組織発生不明腫瘍および胎児性腫瘍などに分類される．ただし，成人大脳半球に発生する神経膠腫は，星細胞系腫瘍と乏突起膠細胞系腫瘍に大別される．そして組織形態を表す指標として，表現は異なるが内容は同じである分化度と異型度が用いられる．分化型（良性）はgradeⅠとⅡ，未分化型（悪性）はgradeⅢとⅣに細分類される．

　神経膠腫には以下のような生物学的特徴があり，これらを十分に理解したうえで治療を考える必要がある．第1に，髄腔内播種はしばしば認められるが，他臓器への転移は稀である．したがって，局所制御が予後を決定する重要な因子となる．第2に，分化型の腫瘍においても浸潤性格が強く，原則として腫瘍の境界が存在しない．Wilson ⁶⁷⁾によれば，約4cmの膠芽腫（glioblastoma，WHO gradeⅣ）の場合，腫瘍から3～4cm離れても細胞の100個に1個は腫瘍細胞であり，さらに驚くべきことに6cm以上離れた対側大脳半球でも，1,000個に1個の割合で腫瘍細胞が存在するとされている．第3に，脳には機能局在があり，eloquent areaの摘出は不可能である．また，放射線治療は線量を増やすことで効果は高まるが，放射線による機能障害が問題となる．第4として，血液脳関門が存在し，これを通過する薬剤が限られる．通過を規定する因子として，脂溶性か水溶性であるかの差と分子量が挙げられる．脂溶性のものほど通過しやすいが，通過後の組織内分布は，逆に水溶性のものほど移行しやすい．他方，分子量が小さいものほど通過しやすい．したがって，一般的に使用されている抗癌剤の大部分は効果が期待できない．このような特徴もあり，悪性神経膠腫では最終的に腫瘍死を免れない．脳腫瘍全国集計調査報告¹⁴⁾にも示されているように，悪性神経膠腫のなかでも膠芽腫の5年相対生存率は過去30年間で向上したとは言いがたく，現在でも7.2％と悲惨な状況である．そんななか，乏突起膠細胞系腫瘍における化学療法に大きな転機が起こった．

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