EFFECTIVENESS OF VASCULAR ENDOTHELIAL GROWTH FACTOR INHIBITORS IN THE TREATMENT OF GLIOBLASTOMA: A SYSTEMATIC REVIEW AND META-ANALYSIS

2019 ◽  
Vol 65 (4) ◽  
pp. 546-555 ◽  
Author(s):  
Vadim Byvaltsev ◽  
Ivan Stepanov ◽  
M. Shameeva ◽  
N. Tetyushkin

The purpose - was to perform a meta-analysis based on the results of randomized controlled trials that examined the efficacy and safety of using anti-VEGF (vascular endothelial growth factor (vascular endothelial growth factor, VEGF)) drugs as an auxiliary treatment for patients with glioblastoma (GBM). Material and methods. A search for randomized controlled trials was conducted in the Pubmed, EMBASE, eLibrary and Cohrane Library databases published from January 2008 to March 2019, which examined the efficacy and safety of using anti-VEGF agents as an auxiliary method of treating GBM patients. The odds ratio (OR) and 95% confidence interval (CI) were used to calculate the overall survival and progression-free survival values. Results. According to the eligibility criteria, 9 randomized controlled trials included in this meta-analysis that examine the results of using anti-VEGF drugs in 3189 patients with GBM. The overall survival rates of patients with GBM using anti-VEGF therapy exceed those in the group of patients with standard therapy without statistically significant differences (OR=0.89, 95% CI: 0.76, 1.04, p=0.13). Significant differences in progression-free survival were noted in favor of anti-VEGF agents (OR=0.70, 95% CI: 0.60, 0.82, p<0.00001). The performed subgroup analysis showed the absence of a statistically significant effect of bevacizumab on the overall survival rates of patients with GBM (OR=0.89, 95% CI: 0.75, 1.06, p=0.20). Using a combination of bevacizumab and standard therapy can significantly improve the progression-free survival rates in patients with GBM (OR=0.63, 95% CI: 0.51, 0.78, p<0.0001). Conclusion. The performed meta-analysis clearly demonstrated that the combination of anti-VEGF agents and standard therapy does not significantly increase the overall survival rate of patients with GBM. However, the use of anti-VEGF drugs statistically significantly improves the values of progression-free survival in patients with GBM.

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Chao Zhang ◽  
Lin Wang ◽  
Chuang Xiong ◽  
Runhan Zhao ◽  
Hao Liang ◽  
...  

Abstract Background In recent years, numerous investigations have been conducted to determine the clinical significance and critical functions of vascular endothelial growth factor (VEGF) in various malignant cancers. The purpose of this meta-analysis was to comprehensively evaluate the prognostic and clinicopathological value of VEGF in patients with osteosarcoma. Methods We performed a systematic literature retrieval of available databases. Odds ratios (ORs) or standard mean difference (SMD) for clinicopathological parameters, hazard ratios (HRs) for overall survival and disease-free survival were calculated to assess the correlation between VEGF expression and prognosis in patients with osteosarcoma. Results A total of 22 studies with 1144 patients were included in our study. Pooled analyses showed that VEGF overexpression predicted worse overall survival (HR, 2.42; 95% CI, 1.87–3.11, p < 0.001) and disease-free survival (HR, 2.604; 95% CI, 1.698–3.995, p < 0.001), respectively. Furthermore, investigation regarding osteosarcoma clinicopathologic characteristics suggested that high VEGF expression was significantly associated with metastasis (OR, 4.39; 95% CI, 2.77–6.95; p < 0.001), clinical stage (OR, 0.73; 95% CI, 0.62–0.87; p < 0.001), and microvessel density (SMD, 3.33, 95% CI,1.57–5.10, p < 0.001), but not associated with tumor location, gender, age, local recurrence, and chemotherapy response. Conclusion Our meta-analysis findings suggest that elevated VEGF expression may be a predictive biomarker for poor prognosis and adverse clinicopathological characteristics in patients with osteosarcoma.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Takahiro Amano ◽  
Hideki Iijima ◽  
Shinichiro Shinzaki ◽  
Taku Tashiro ◽  
Shuko Iwatani ◽  
...  

Abstract Background The efficacy and safety of bevacizumab-containing chemotherapy for patients with metastatic duodenal and jejunal adenocarcinoma (mDJA) are unclear. The present study aimed to evaluate the efficacy of bevacizumab and to explore immunohistochemical markers that can predict the efficacy of bevacizumab for patients with mDJA. Methods This multicentre study included patients with histologically confirmed small bowel adenocarcinoma who received palliative chemotherapy from 2008 to 2017 at 15 hospitals. Immunostaining was performed for vascular endothelial growth factor-A (VEGF-A), TP53, Ki67, β-catenin, CD10, MUC2, MUC5AC, MUC6, and mismatch repair proteins. Results A total of 74 patients were enrolled, including 65 patients with mDJA and 9 with metastatic ileal adenocarcinoma. Patients with mDJA who received platinum-based chemotherapy with bevacizumab as first-line treatment tended to have a longer progression-free survival and overall survival than those treated without bevacizumab (P = 0.075 and 0.077, respectively). Multivariate analysis extracted high VEGF-A expression as a factor prolonging progression-free survival (hazard ratio: 0.52, 95% confidence interval: 0.30–0.91). In mDJA patients with high VEGF-A expression, those who received platinum-based chemotherapy with bevacizumab as a first-line treatment had significantly longer progression-free survival and tended to have longer overall survival than those treated without bevacizumab (P = 0.025 and P = 0.056, respectively), whereas no differences were observed in mDJA patients with low VEGF-A expression. Conclusion Immunohistochemical expression of VEGF-A is a potentially useful biomarker for predicting the efficacy of bevacizumab-containing chemotherapy for patients with mDJA.


2021 ◽  
Author(s):  
Takahiro Amano ◽  
Hideki Iijima ◽  
Shinichiro Shinzaki ◽  
Taku Tashiro ◽  
Shuko Iwatani ◽  
...  

Abstract Background: The efficacy and safety of bevacizumab-containing chemotherapy for patients with metastatic duodenal and jejunal adenocarcinoma (mDJA) are unclear. The present study aimed to evaluate the efficacy of bevacizumab and to explore immunohistochemical markers that can predict the efficacy of bevacizumab for patients with mDJA.Methods: This multicentre study included patients with histologically confirmed small bowel adenocarcinoma who received palliative chemotherapy from 2008 to 2017 at 15 hospitals. Immunostaining was performed for vascular endothelial growth factor A (VEGF-A), TP53, Ki67, β-catenin, CD10, MUC2, MUC5AC, MUC6, and mismatch repair proteins.Results: A total of 74 patients were enrolled, including 65 patients with mDJA and 9 with metastatic ileal adenocarcinoma. Patients with mDJA who received platinum-based chemotherapy with bevacizumab as first-line treatment tended to have a longer progression-free survival and overall survival than those treated without bevacizumab (P = 0.075 and 0.077, respectively). Multivariate analysis extracted high VEGF-A expression as a factor prolonging progression-free survival (hazard ratio: 0.52, 95% confidence interval: 0.30-0.91). In mDJA patients with high VEGF-A expression, those who received platinum-based chemotherapy with bevacizumab as a first-line treatment had significantly longer progression-free survival and tended to have longer overall survival than those treated without bevacizumab (P = 0.025 and P = 0.056, respectively), whereas no differences were observed in mDJA patients with low VEGF-A expression. Conclusion: Immunohistochemical expression of VEGF-A is a potentially useful biomarker for predicting the efficacy of bevacizumab-containing chemotherapy for patients with mDJA.


Author(s):  
Takao Kamai ◽  
Toshiki Kijima ◽  
Toyonori Tsuzuki ◽  
Akinori Nukui ◽  
Hideyuki Abe ◽  
...  

Abstract Background Adenosine and its adenosine 2A receptors (A2AR) mediate the immunosuppressive mechanism by which tumors escape immunosurveillance and impede anti-tumor immunity within the tumor microenvironment. However, we do not know whether the adenosine pathway (CD39/CD73/A2AR) plays a role in renal cell carcinoma (RCC). Therefore, we studied the role of immunosuppression in RCC by assessing the adenosine pathway in patients with RCC treated with anti-vascular endothelial growth factor (anti-VEGF) agents or immune checkpoints inhibitors (ICIs) or both. Methods In 60 patients with metastatic RCC, we examined the expression of CD39, CD73, A2AR, and programmed cell death 1 ligand 1 (PD-L1) immunohistochemically in surgically resected tumor tissues and studied the clinicopathological characteristics of these patients. Patients were treated by cytoreductive nephrectomy with systemic therapy with anti-VEGF agent or a combination of the ICIs anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibody and programmed cell death 1 (PD-1) antibody. Results Increased expression of A2AR in the primary tumors was associated with metastatic profiles. Patients treated with anti–PD-1 antibody in monotherapy, a combination of anti-PD-1 and anti-CTLA4 antibodies, or anti-VEGF agents showed better response and longer overall survival if the primary tumor had higher PD-L1 expression and lower A2AR expression. In Cox multivariate regression analysis, higher expression of A2AR was associated with shorter overall survival. Conclusions Our findings suggest that the expression of A2AR and PD-L1 in the primary tumors in RCC might predict the outcomes of treatment with anti-VEGF agents and ICIs and that the A2AR pathway might be a molecular target for immunotherapy.


2020 ◽  
Vol 2 (2) ◽  
pp. 71-85
Author(s):  
Isabel Novo ◽  
Bárbara Campos ◽  
Filipa Pinto-Ribeiro ◽  
Sandra F. Martins

Background: the presence of liver metastasis in colorectal cancer (CRC) remains one of the most significant prognostic factors. Objective: systematically review the results of studies evaluating the benefit of adding bevacizumab to a normal chemotherapy regime in the survival of patients with colorectal-cancer liver metastasis (CRLM). Search methods: Pubmed and Google Scholar databases were searched for eligible articles (from inception up to the 2 April 2019). Inclusion criteria: studies including patients with CRLM receiving anti-vascular endothelial growth factor (VEGF; bevacizumab) as treatment, overall survival as an outcome; regarding language restrictions, only articles in English were accepted. Main results: Eleven studies met the inclusion criteria. In 73% of these cases, chemotherapy with bevacizumab was an effective treatment modality for treating CRLM, and its administration significantly extended both overall survival (OS) and/or progression-free survival (PFS). Nevertheless, three articles showed no influence on survival rates of bevacizumab-associated chemotherapy. Author conclusions: It is necessary to standardize methodologies that aim to evaluate the impact of bevacizumab administration on the survival of patients with CRLM. Furthermore, follow-up time and the cause of a patient’s death should be recorded, specified, and cleared in order to better calculate the survival rate and provide a comparison between the produced literature.


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