Kemoterapi temozolomide pada glioblastoma multiforme
https://doi.org/10.22146/bns.v19i3.73901 Fidha Rahmayani(1*), Pernodjo Dahlan(2), Subagya Subagya(3)
(1) Departemen Neurologi, Fakultas Kedokteran, Universitas Lampung, Lampung
(2) Departemen Neurologi, Fakultas Kedokteran, Kesehatan Masyarakat dan Keperawatan, Universitas Gadjah Mada, Yogyakarta
(3) Departemen Neurologi, Fakultas Kedokteran, Kesehatan Masyarakat dan Keperawatan, Universitas Gadjah Mada, Yogyakarta
(*) Corresponding Author
Abstract
Glioblastoma multiforme is the most common astrocytoma subtype in adult with the average incidence 3.2 new cases per 100.000 per year. This tumour has natural characteristic as aggressive, infiltrative and destructive whose giving variable symptoms depend on size of tumour, location, mass effect and increase intracranial pressure. The current standard of care for newly diagnosed GBM patients includes surgery, radiotherapy and adjuvant temozolomide (TMZ).
Chemotherapy concomitant and adjuvant with TMZ treatment conferring a median survival time of 14.6 months compared with 12.1 months for patients receiving radiotherapy alone. TMZ is an imidazotetrazine derivate, has cytotoxic effect by methylates DNA specific position. TMZ is an orally available and rapidly absorbed intact, penetrates blood brain barrier and highly concentrated in cerebrospinal fluid.
One of the major challenges coming from temozolomide chemotherapy is resistancy to this alkylating agents. Mechanism of resistance to alkylating agents is mediated by the DNA repair enzyme O6-methylguanine methyltransferase (MGMT) which repairs O-methylguanine adducts DNA result repair DNA lesion. MGMT promoter methylation status play an important role for predict respons of tumour GBM treated with TMZ so could be a strong prognostic biomarker in GBM.
ABSTRAK
Glioblastoma multiforme (GBM) adalah subtipe astrositoma yang paling sering dijumpai pada dewasa dengan rerata insiden sebanyak 3,2 kasus baru per 100.000 penduduk per tahun. Tumor ini memiliki sifat dasar agresif, sangat invasif dan destruktif pada jaringan otak dan mengakibatkan manifestasi klinis yang bervariasi tergantung pada lokasi anatomis tumor, efek masa, serta peningkatan tekanan intrakranial. Standar penatalaksanaan GBM yang saat ini digunakan adalah dengan operasi reseksi, dilanjutkan dengan radioterapi dan kemoterapi.
Kemoterapi concomitant dan adjuvant dengan menambahkan temozolomide sepanjang dan setelah radioterapi menjadi terapi standar GBM sejak tahun 2005, yang dapat meningkatkan rerata kelangsungan hidup dari 12,1 bulan menjadi 14,6 bulan. Temozolomide adalah generasi kedua dari derivat imidazotetrazine, yang memiliki efek sitotoksik dengan mekanisme kerja memetilasi situs DNA spesifik. TMZ dikonsumsi per oral dan diabsorbsi secara cepat, menembus sawar darah otak, dan mencapai konsentrasi yang tinggi di dalam cairan otak.
Salah satu permasalahan kemoterapi TMZ adalah resistensi terhadap alkylating agent ini yang diperantarai protein O6-methylguanine–DNA methyltransferase (MGMT). Mekanisme kerja protein ini adalah melepas gugus metil dari posisi O6-guanin pada basa DNA sehingga terjadi perbaikan lesi DNA. Pada GBM, status metilasi promotor gen protein ini memiliki peranan untuk menentukan respons sel tumor terhadap kemoterapi zat pengalkil dan dapat memprediksi keberhasilan kemoterapi TMZ pada pasien. Selain itu status metilasi promotor gen MGMT dapat digunakan sebagai dasar pemilihan terapi GBM, sehingga status metilasi MGMT dapat digunakan sebagai biomarker prognostik dan prediktif pada GBM yang diterapi dengan TMZ.
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Hess KR, Broglio KR, Bondy ML. Adult glioma incidence trends in the United States, 1977–2000. Cancer: Interdisciplinary International Journal of the American Cancer Society. 2004;101(10):2293-2299.
Ostrom QT, Gittleman H, Farah P, Ondracek A, Chen Y, Wolinsky Y, et al. CBTRUS statistical report: Primary brain and central nervous system tumors diagnosed in the United States in 2006-2010. Neuro-oncology. 2013;15(suppl_2):ii1-ii56.
Armstrong TS, Wefel JS, Wang M, Gilbert MR, Won M, Bottomley A, et al. Net clinical benefit analysis of radiation therapy oncology group 0525: a phase III trial comparing conventional adjuvant temozolomide with dose-intensive temozolomide in patients with newly diagnosed glioblastoma. Journal of Clinical Oncology. 2013;31(32):4076–4084.
Carlsson SK, Brothers SP, Wahlestedt C. Emerging treatment strategies for glioblastoma multiforme. EMBO molecular medicine. 2014;6(11):1359-1370.
Ahmed R, Oborski MJ, Hwang M, Lieberman FS, Mountz JM. Malignant gliomas: current perspectives in diagnosis, treatment, and early response assessment using advanced quantitative imaging methods. Cancer Management and Research. 2014;6:149-170.
Weller M. Novel diagnostic and therapeutic approaches to malignant glioma. Swiss Medical Weekly. 2011;141:w13210.
Hottinger AF, Stupp R, Homicsko K. Standards of care and novel approaches in the management of glioblastoma multiforme. Chinese Journal of Cancer. 2014;33(1):32-39.
Arvold ND, Reardon DA. Treatment options and outcomes for glioblastoma in the elderly patient. Clinical Interventions in Aging. 2014;9:357–367.
Bobola MS, Alnoor M, Chen JY, Kolstoe DD, Silbergeld DL, Rostomily RC, et al. O6-methylguanine-DNA methyltransferase activity is associated with response to alkylating agent therapy and with MGMT promoter methylation in glioblastoma and anaplastic glioma. BBA clinical. 2015;3:1-10.
Kohler BA, Ward E, McCarthy BJ, Schymura MJ, Ries LAG, Eheman C, et al. Annual report to the nation on the status of cancer, 1975-2007, featuring tumors of the brain and other nervous system. Journal of the National Cancer Institute. 2011;103(9):714–736.
Porter A. A dead end: A review of glioblastoma multiforme.
Eukaryon. 2012;8:64-8.
Goldlust SA, Turner GM, Goren JF, Gruber ML. Glioblastoma multiforme: multidisciplinary care and advances in therapy. Hospital Physician. 2008;1:9-23.
Zhang X, Zhang WE, Cao WD, Cheng G, Zhang YQ.
Glioblastoma multiforme: Molecular characterization and current treatment strategy. Experimental and Therapeutic Medicine. 2012;3(1):9-14.
Sanghera P, Rampling R, Haylock B, Jefferies S, McBain C, Rees JH, et al. The concepts, diagnosis and management of early imaging changes after therapy for glioblastomas. Clinical Oncology. 2012;24(3):216-227.
Murakami R, Hirai T, Sugahara T, Fukuoka H, Toya R, Nishimura S, et al. Grading astrocytic tumors by using apparent diffusion coefficient parameters: superiority of a one-versus two-parameter pilot method. Radiology. 2009;251(3):838-845.
Kao HW, Chiang SW, Chung HW, Tsai FY, Chen CY. Advanced MR imaging of gliomas: an update. BioMed Research International. 2013;2013.
Yu TG, Feng Y, Feng XY, Dai JZ, Qian HJ, Huang Z. Prognostic factor from MR spectroscopy in rat with astrocytic tumour during radiation therapy. The British journal of radiology. 2015;88(1045):20140418.
Adamson C, Kanu OO, Mehta AI, Di C, Lin N, Mattox AK, et al. Glioblastoma multiforme: a review of where we have been and where we are going. Expert Opinion on Investigational Drugs. 2019;18(8):1061–1083.
Schwartzbaum JA, Fisher JL, Aldape KD, Wrensch M. Epidemiology and molecular pathology of glioma. Nature Clinical Practice Neurology. 2006;2(9):494-503.
Maher EA, Furnari FB, Bachoo RM, Rowitch DH, Louis DN, Cavenee WK, et al. Malignant glioma: genetics and biology of a grave matter. Genes & Development. 2001;15(11):1311-1333.
Kleihues P, Ohgaki H. Phenotype vs genotype in the evolution of astrocytic brain tumors. Toxicologic Pathology. 2000;28(1):164- 170.
Stupp R, Mason WP, Van Den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. New England Journal of Medicine. 2005;352(10):987-996.
Chang L, Su J, Jia X, Ren H. Treating malignant glioma in Chinese patients: update on temozolomide. OncoTargets and Therapy. 2014;7:235–244.
Wang Q, Wei L, Shirley L, Jason SC, Olli AJ, Erika K, et al. Mechanisms of Chemoresistance in Malignant Glioma. 2014;27(3):380–392.
Wang K, Wang YY, Ma J, Wang JF, Li SW, Jiang T, et al. Prognostic value of MGMT promoter methylation and TP53 mutation in glioblastomas depends on IDH1 mutation. Asian Pacific Journal of Cancer Prevention. 2015;15(24):10893-10898.
Minniti G, Muni R, Lanzetta G, Marchetti P, Enrici RM. Chemotherapy for glioblastoma: current treatment and future perspectives for cytotoxic and targeted agents. Anticancer Research. 2009;29(12):5171-5184.
Buckner JC, Shaw EG, Pugh SL, Chakravarti A, Gilbert MR, Barger GR, et al. Radiation plus procarbazine, CCNU, and vincristine in low-grade glioma. New England Journal of Medicine. 2016;374(14):1344-1355.
Darkes MJM, GL Plosker, B Jarvis. Temozolomide: a review of its use in tne treatment of malignant gliomas. American Journal Cancer. 2002;1(1):55–80.
Koukourakis GV, Kouloulias V, Zacharias G, Papadimitriou C, Pantelakos P, Maravelis G, et al. Temozolomide with radiation therapy in high grade brain gliomas: pharmaceuticals considerations and efficacy; a review article. Molecules. 2009;14(4):1561-1577.
Newlands ES, GR Blackledge, JA Slack, GJ Rustin, DB Smith, NS Stuart, et al. Phase i trial of temozolomide (CCRG 81045: M&B 39831: NSC 362856). British Journal of Cancer. 1992;65(2):287–291.
Friedman HS, Kerby T, Calvert H. Temozolomide and treatment of malignant glioma. Clinical Cancer Research. 2000;6(7):2585- 2597.
Hegi ME, Diserens AC, Gorlia T, Hamou MF, De Tribolet N, Weller M, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. New England Journal of Medicine. 2005;352(10):997-1003.
Wick W, Weller M, Van Den Bent M, Sanson M, Weiler M, Von Deimling A, et al. MGMT testing—the challenges for biomarker-based glioma treatment. Nature Reviews Neurology. 2014;10(7):372-385.
Christians A, Hartmann C, Benner A, Meyer J, von Deimling A, Weller M, et al. Prognostic value of three different methods of MGMT promoter methylation analysis in a prospective trial on newly diagnosed glioblastoma. PloS One. 2012;7(3):e33449.
Bae SH, Park MJ, Lee MM, Kim TM, Lee SH, Cho SY, et al. Toxicity profile of temozolomide in the treatment of 300 malignant glioma patients in Korea. Journal of Korean medical science. 2014;29(7):980.
Dixit S, Baker L, Walmsley V, Hingorani M. Temozolomide- related idiosyncratic and other uncommon toxicities: a systematic review. Anti-cancer drugs. 2012;23(10):1099-1106.
DOI: https://doi.org/10.22146/bns.v19i3.73901
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