Phase II Study of Bevacizumab in Combination with Sorafenib in Recurrent Glioblastoma (N0776): A North Central Cancer Treatment Group Trial
| العنوان: | Phase II Study of Bevacizumab in Combination with Sorafenib in Recurrent Glioblastoma (N0776): A North Central Cancer Treatment Group Trial |
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| المؤلفون: | Jan C. Buckner, Shaji Kumar, Evanthia Galanis, Caterina Giannini, Kurt A. Jaeckle, Patrick J. Flynn, Jacqueline M. Lafky, Joon H. Uhm, Donald W. Northfelt, S. Keith Anderson, Teresa K. Kimlinger, Timothy J. Kaufmann |
| المصدر: | Clinical Cancer Research. 19:4816-4823 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Adult, Male, Niacinamide, Vascular Endothelial Growth Factor A, Sorafenib, Oncology, Cancer Research, medicine.medical_specialty, Bevacizumab, Angiogenesis, Phases of clinical research, Antibodies, Monoclonal, Humanized, Polymorphism, Single Nucleotide, Disease-Free Survival, Article, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, medicine, Humans, Aged, Proportional Hazards Models, Biologic marker, Brain Neoplasms, business.industry, Phenylurea Compounds, Therapeutic effect, Cancer, Middle Aged, Hypoxia-Inducible Factor 1, alpha Subunit, Neoplastic Cells, Circulating, medicine.disease, Vascular Endothelial Growth Factor Receptor-2, Surgery, Toxicity, Female, Neoplasm Recurrence, Local, Glioblastoma, business, medicine.drug |
| الوصف: | Purpose: We hypothesized that vertical blockade of VEGF signaling by combining bevacizumab with sorafenib in patients with recurrent glioblastoma would result in a synergistic therapeutic effect. We also investigated whether VEGF, VEGFR2 and hypoxia-inducible factor-1α single-nucleotide polymorphisms (SNP), circulating biomarkers of angiogenesis, and MRI markers such as apparent diffusion coefficient (ADC) are correlated with treatment efficacy and/or toxicity. Experimental Design: Patients received bevacizumab (5 mg/kg every 2 weeks) with sorafenib (200 mg twice a day, weekly, days 1–5; group A). Due to toxicity, the starting sorafenib dose was subsequently modified to 200 mg every day (group B). Results: Fifty-four patients were enrolled: 19 patients in group A and 35 in group B. Objective response rate was 18.5% with median duration of 6.7 months (range 0.5–24.1 months). Six-month progression-free survival (PFS6) was 20.4% (11/54), and median overall survival (OS) was 5.6 months [95% confidence interval (CI), 4.7–8.2]; outcome was similar between the two dose groups. We identified SNPs in the VEGF and VEGFR2 promoter regions, which were associated with PFS6 (P < 0.022). Among molecular markers of angiogenesis, a higher log2 baseline level of stromal cell–derived factor-1 was associated with PFS6 success (P = 0.04). Circulating endothelial cells decreased during treatment with subsequent increase at disease progression (P = 0.022). Imaging analysis showed a trend associating ADC-L with poor outcome. Conclusions: The bevacizumab/sorafenib combination did not improve outcome of patients with recurrent glioblastoma versus historic bevacizumab-treated controls. Biologic markers of response and resistance to bevacizumab in gliomas were identified which merit prospective validation. Clin Cancer Res; 19(17); 4816–23. ©2013 AACR. |
| تدمد: | 1557-3265 1078-0432 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::77bcc6b23403f955f82ac59e0e9630ecTest https://doi.org/10.1158/1078-0432.ccr-13-0708Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....77bcc6b23403f955f82ac59e0e9630ec |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15573265 10780432 |
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