Neurological Surgery 脳神経外科35巻5号

2007年05月発行

総説

悪性神経膠腫の化学療法

著者： 永根基雄¹

所属機関： ¹杏林大学医学部脳神経外科

ページ範囲：P.433 - P.450

Ⅰ．はじめに

　神経膠腫を主とする悪性脳腫瘍は，胚芽腫など一部の腫瘍を除き癌薬物療法（化学療法）の有効性が一般に低く，延命効果も不十分な群に属すると考えられている．Melanoma，膵癌，肝癌などと同様に，この群の悪性腫瘍に対しての抗悪性腫瘍薬の使用に際しては，臨床試験における実施が望ましく，実地医療の場ではその適応を慎重に検討する必要がある．しかし，現実には悪性脳腫瘍の発生頻度は低く，希少腫瘍の群に含められ，多くの症例を短期間に蓄積して医学的エビデンスレベルの高い臨床試験の結果を出していくのは容易なことではない．特に本邦では，2005年初頭までは神経膠腫に対して保険適応が認可されていた薬剤は，ACNU（nimustine hydrochloride），MCNU，bleomycin，interferon-βに限られていたため，大学病院などの一部の施設を除き多剤併用療法を行うことも困難であった．また，これらの薬剤も有効性のエビデンスには乏しく，各大学などで様々な併用化学療法が小規模に実施されていたのが実情である．

　一方，近年の基礎・臨床研究から，悪性神経膠腫の中でも乏突起膠腫系腫瘍など化学療法に感受性の比較的高い腫瘍グループが存在し，治療反応性や予後を規定する特異的な遺伝子変異・マーカーの存在が明らかにされ，またO⁶-methylguanine-DNA methyltransferase（MGMT）を中心とした薬剤耐性機序の解明と予後との関連が示されるなど，臨床的に意義深い知見が蓄積されてきている．2005年2月にPCV療法に使用されるprocarbazine（PCZ），vincristine（VCR）が神経膠腫に対して適用拡大されたのに続き，2006年7月には世界的に悪性神経膠腫治療の主流となりつつあるtemozolomide（TMZ）が，本邦での神経膠腫への新規治療薬としては約20年ぶりの承認がなされたことなど，脳腫瘍に対する化学療法は大きな転換期を迎えたといえよう．

　神経膠腫以外にも，髄芽腫・胚細胞腫瘍・リンパ腫など放射線治療や化学療法に感受性を示す腫瘍群では，標準的治療法の確立に伴い，飛躍的に治療成績の向上が認められ，悪性脳腫瘍治療における化学療法の果たす役割の重要性が増してきているのも事実である．特に癌薬物療法に対する関心は高く，学会的にも専門医制度の導入が検討・実施されており，今後悪性脳腫瘍の化学療法を施行する際にも，より専門的知識と経験が要求される時代の到来が予想される．本稿では，特に神経膠腫治療成績のこれまでに得られているエビデンスと現状，耐性の機序と今後の方向性につき述べる．

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