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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DOI: https://doi.org/10.22146/bns.v19i3.73901
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