BRAIN and NERVE－神経研究の進歩61巻7号

2009年07月発行

特集 脳腫瘍研究の最前線―遺伝子解析から治療まで

テモゾロミドによるグリオーマ治療

著者： 西川亮¹

所属機関： ¹埼玉医科大学国際医療センター脳・脊髄腫瘍科

ページ範囲：P.849 - P.854

文献概要

はじめに

　膠芽腫（glioblastoma：GBM）の初期治療において，放射線照射にテモゾロミド（temozolomide）を併用することが世界的な標準的治療となったのは2005年である^1）。わが国においてもテモゾロミドは2006年9月に発売となり，瞬く間に悪性グリオーマ治療薬として広く使われるようになった。

　本稿では今一度テモゾロミドの投与法の原理について確認した後，新しい投与方法の開発，積み残されている問題点などについて概説する。

参考文献

1) Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, et al: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352: 987-996, 2005

2) Kil WJ, Cerna D, Burgan WE, Beam K, Carter D, et al: In vitro and in vivo radiosensitization induced by the DNA methylating agent temozolomide. Clin Cancer Res 14: 931-938, 2008

3) 永根基雄: MGMTとtemozolomide（TMZ). 脳2112: 38-43, 2009

-alkylguanine-DNA alkylstansrerase activity with protracted temozolomide schedules. Br J Cancer 88: 1004-1011, 2003

5) Kurzen H, Schmitt S, Näeher H, Möhler T: Inhibition of angiogenesis by non-toxic doses of temozolomide. Anticancer Drugs 14: 515-522, 2003

6) 西川　亮, 澁井壯一郎, 丸野元彦, 杉山一彦, 佐藤慎哉, 他: 初回再発の退形成性星細胞腫患者に対するTemozolomide単剤投与の有効性および安全性の検討―多施設共同第Ⅱ相試験. 癌と化療33: 1279-1285, 2006

7) Chinot OL, Barrié M, Fuentes S, Eudes N, Lancelot S, et al: Correlation between O6-methylguanine-DNA methyltransferase and survival in inoperable newly diagnosed glioblastoma patients treated with neoadjuvant temozolomide. J Clin Oncol 25: 1470-1475, 2007

8) Brandes AA, Tosoni A, Cavallo G, Bertorelle R, Gioia V, et al: Temozolomide 3 weeks on and 1 week off as first-line therapy for recurrent glioblastoma: phase II study from gruppo italiano cooperativo di neuro-oncologia (GICNO). Br J Cancer 95: 1155-1160, 2006

9) Perry JR, Rizek P, Cashman R, Morrison M, Morrison T: Temozolomide rechallenge in recurrent malignant gliomas by using a continuous temozolomide schedule. Cancer 113: 2152-2157, 2008

10) Yung WK, Albright RE, Olson J, Fredericks R, Fink K, et al: A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relaplse. Br J Cancer 83: 588-593, 2000

11) Keime-Guibert F, Chinot O, Taillandier L, Cartalat-Carel S, Frenay M, et al: Radiotherapy for glioblastoma in the elderly. New Engl J Med 356: 1527-1535, 2007

12) Roa W, Brasher PM, Bauman G, Anthes M, Bruera E, et al: Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomized clinical trial. J Clin Oncol 22: 1583-1588, 2004

13) Kaloshi G, Benouaich-Amiel A, Diakite F, Taillibert S, Lejeune J, et al: Temozolomide for low-grade gliomas: Predictive impact of 1p/19q loss on response and outcome. Neurology 68: 1831-1836, 2007.

14) Vogelbaum MA, Berkey B, Peereboom D, Macdonald D, Giannini C, et al: Phase II trial of preirradiation and concurrent temozolomide in patients with newly diagnosed anaplastic oligodendrogliomas and mixed anaplastic oligoastrocytomas: RTOG BR0131. NeuroOncol 11: 167-175, 2009

International Research Update Meeting, Barcelona, Dec 1-2, 2006

16) Herrlinger U, Rieger J, Koch D, Loeser S, Blaschke B, et al: Phase II trial of lomustine plus temozolomide chemotherapy in addition to radiotherapy in newly diagnosed glioblastoma: UKT-03. J Clin Oncol 24: 4412-4417, 2006

17) Hegi ME, Diserens AC, Gorlia T, Hamou T, de Tribolet N, et al: MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352: 997-1003, 2005

18) Noronha V, Berliner N, Ballen KK, Lacy J, Kracher J, et al: Treatment-related myelodysplasia/AML in a patient with a history of breast cancer and an oliogodendroglioma treated with temozolomide: Case study and review of the literature. NeuroOncol 8: 280-283, 2006

19) Dufour C, Da Costa L, Auger N, Jullien M, Bhangoo R, et al: Treatment-related myelodysplastic syndrome after temozolomide use in a child. J Pediatr Hematol Oncol 30: 857-859, 2008

20) Su YW, Chang MC, Chiang MF, Hsieh RK: Treatment-related myelodysplastic syndrome after temozolomide for recurrent high-grade gliomas. J Neurooncol 71: 315-318, 2005

21) Chamberlain MC, Raizer J: Extended exposure to alkylator chemotherapy: delayed appearance of myelodysplasia. J Neurooncol 93: 229-232, 2009