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Neoplasma ; 66(2): 288-293, 2019 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-30569719

RESUMO

Glioma is the most common brain malignancy. Standard first-line therapy for glioma includes surgery, radiotherapy and systemic administration of temozolomide. However, temozolomide does not reach the brain in sufficient doses when administered orally and has poor efficiency in more than half of the patients. Strategies to improve the treatment of glial malignancies are therefore needed. We have recently developed a system (Temodex) for local administration of temozolomide by encapsulating the drug in a biologically inert matrix. Here, we assessed the effect of Temodex in combination with standard therapy in a small-scale clinical study. Since the efficacy of temozolomide therapy is known to depend on the methylation status of the O6-methylguanine-DNA methyltransferase gene (MGMT) promoter, we also analyzed whether the effect of Temodex was influenced by the methylation status of MGMT. Our data show that the combination of standard therapy and Temodex was more efficient than standard therapy alone, promoting the overall patient survival by up to 33 weeks. Moreover, the efficacy of Temodex was not dependent on the methylation status of MGMT. Local Temodex administration in combination with standard therapy thereby emerges as a novel therapeutic option, with applicability that is independent on the methylation status of the MGMT promoter.


Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Portadores de Fármacos/química , Glioma/tratamento farmacológico , Temozolomida/administração & dosagem , Metilação de DNA , Metilases de Modificação do DNA/química , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/química , Enzimas Reparadoras do DNA/genética , Humanos , Regiões Promotoras Genéticas , Proteínas Supressoras de Tumor/química , Proteínas Supressoras de Tumor/genética
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