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Clin Transl Oncol ; 21(10): 1364-1373, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30798512

RESUMO

PURPOSE: Patients with recurrent glioblastoma (rGBM) have a poor prognosis, with survival ranging from 25 to 40 weeks. Antiangiogenic agents are widely used, showing a variable response. In this study, we explored the efficacy of carmustine plus bevacizumab (BCNU/Bev) for treating rGBM. METHODS/PATIENTS: In this study, we assessed 59 adult patients with histologically confirmed rGBM who were treated with BCNU/Bev as second-line regimen. The response rate (RR), progression-free survival (PFS) and overall survival (OS) were evaluated according to their molecular expression profile, including CD133 mRNA expression, MGMT methylation (pMGMT), PDGFR amplification, YKL40 mRNA expression, IDH1/2 condition, p53 and EGFRvIII mutation status. RESULTS: Median follow-up was 18.6 months, overall RR to the combination was 56.3%, and median PFS was 9.0 months (95% CI 8.0-9.9). OS from time of diagnosis was 21.0 months (95% CI 13.2-28.7) and from starting BCNU/Bev it was 10.7 months (95% CI 9.5-11.8). IDH1/2 mutations were found in 30.5% of the patients, pMGMT in 55.9% and high CD133 mRNA expression in 57.6%. Factors which positively affected PFS included performance status (p = 0.015), IDH+ (p = 0.05), CD133 mRNA expression (p = 0.009) and pMGMT+ (p = 0.007). OS was positively affected by pMGMT+ (p = 0.05). Meanwhile, YKL40 negatively affected PFS (p = 0.01) and OS (p = 0.0001). Grade ≥ 3 toxicities included hypertension (22%) and fatigue (12%). CONCLUSIONS: BCNU/Bev is a safe and tolerable treatment for rGBM. Patients with MGMT+/IDH+ derive the greatest benefit from the treatment combination in the second-line setting. Nonetheless, high YKL40 expression discourages the use of antiangiogenic therapy.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Carmustina/uso terapêutico , Glioblastoma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Antígeno AC133/genética , Antígeno AC133/metabolismo , Adulto , Idoso , Inibidores da Angiogênese/efeitos adversos , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Bevacizumab/efeitos adversos , Neoplasias Encefálicas/irrigação sanguínea , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidade , Carmustina/efeitos adversos , Proteína 1 Semelhante à Quitinase-3/genética , Colômbia , Metilases de Modificação do DNA/metabolismo , Enzimas Reparadoras do DNA/metabolismo , Esquema de Medicação , Feminino , Genes erbB-1 , Genes p53 , Glioblastoma/irrigação sanguínea , Glioblastoma/genética , Glioblastoma/mortalidade , Humanos , Isocitrato Desidrogenase/genética , Masculino , Metilação , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/irrigação sanguínea , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/mortalidade , Intervalo Livre de Progressão , RNA Mensageiro/metabolismo , Receptores do Fator de Crescimento Derivado de Plaquetas/genética , Análise de Sobrevida , Proteínas Supressoras de Tumor/metabolismo , Adulto Jovem
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