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Clin Transl Oncol ; 21(10): 1364-1373, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30798512

RESUMEN

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.


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Bevacizumab/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Carmustina/uso terapéutico , Glioblastoma/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Antígeno AC133/genética , Antígeno AC133/metabolismo , Adulto , Anciano , Inhibidores de la Angiogénesis/efectos adversos , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Bevacizumab/efectos adversos , Neoplasias Encefálicas/irrigación sanguínea , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidad , Carmustina/efectos adversos , Proteína 1 Similar a Quitinasa-3/genética , Colombia , Metilasas de Modificación del ADN/metabolismo , Enzimas Reparadoras del ADN/metabolismo , Esquema de Medicación , Femenino , Genes erbB-1 , Genes p53 , Glioblastoma/irrigación sanguínea , Glioblastoma/genética , Glioblastoma/mortalidad , Humanos , Isocitrato Deshidrogenasa/genética , Masculino , Metilación , Persona de Mediana Edad , Mutación , Recurrencia Local de Neoplasia/irrigación sanguínea , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/mortalidad , Supervivencia sin Progresión , ARN Mensajero/metabolismo , Receptores del Factor de Crecimiento Derivado de Plaquetas/genética , Análisis de Supervivencia , Proteínas Supresoras de Tumor/metabolismo , Adulto Joven
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