Anti-VEGF drugs and clinical trials

2012 ◽  
pp. 243-256
Keyword(s):  
Clinical Trials ◽  
Anti Vegf

New Anti-VEGF Drugs in Ophthalmology

2020 ◽  
Vol 21 (12) ◽  
pp. 1194-1200
Author(s):  
Claudio Campa
Keyword(s):  
Clinical Trials ◽  
Delivery System ◽  
Clinical Development ◽  
Advanced Stage ◽  
Phase 3 ◽  
Anti Vegf

: This review focuses on 5 new anti-VEGF drugs in the advanced stage of clinical development (i.e., phase 3): conbercept, brolucizumab, port delivery system with ranibizumab, abicipar pegol and faricimab. : Results of clinical trials and the advantages of each drug compared to the available molecules are discussed in detail.

Lessons from phase III clinical trials on anti-VEGF therapy for cancer

2006 ◽  
Vol 3 (1) ◽  
pp. 24-40 ◽  
Author(s):  
Rakesh K Jain ◽  
Dan G Duda ◽  
Jeffrey W Clark ◽  
Jay S Loeffler
Keyword(s):  
Clinical Trials ◽  
Phase Iii ◽  
Phase Iii Clinical Trials ◽  
Anti Vegf

scholarly journals Normalization of the Vasculature for Treatment of Cancer and Other Diseases

2011 ◽  
Vol 91 (3) ◽  
pp. 1071-1121 ◽  
Author(s):  
Shom Goel ◽  
Dan G. Duda ◽  
Lei Xu ◽  
Lance L. Munn ◽  
Yves Boucher ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Solid Tumors ◽  
Tumor Angiogenesis ◽  
Interstitial Fluid ◽  
Tumor Hypoxia ◽  
Fluid Pressure ◽  
Tumor Vasculature ◽  
Interstitial Fluid Pressure ◽  
Vascular Normalization ◽  
Anti Vegf

New vessel formation (angiogenesis) is an essential physiological process for embryologic development, normal growth, and tissue repair. Angiogenesis is tightly regulated at the molecular level. Dysregulation of angiogenesis occurs in various pathologies and is one of the hallmarks of cancer. The imbalance of pro- and anti-angiogenic signaling within tumors creates an abnormal vascular network that is characterized by dilated, tortuous, and hyperpermeable vessels. The physiological consequences of these vascular abnormalities include temporal and spatial heterogeneity in tumor blood flow and oxygenation and increased tumor interstitial fluid pressure. These abnormalities and the resultant microenvironment fuel tumor progression, and also lead to a reduction in the efficacy of chemotherapy, radiotherapy, and immunotherapy. With the discovery of vascular endothelial growth factor (VEGF) as a major driver of tumor angiogenesis, efforts have focused on novel therapeutics aimed at inhibiting VEGF activity, with the goal of regressing tumors by starvation. Unfortunately, clinical trials of anti-VEGF monotherapy in patients with solid tumors have been largely negative. Intriguingly, the combination of anti-VEGF therapy with conventional chemotherapy has improved survival in cancer patients compared with chemotherapy alone. These seemingly paradoxical results could be explained by a “normalization” of the tumor vasculature by anti-VEGF therapy. Preclinical studies have shown that anti-VEGF therapy changes tumor vasculature towards a more “mature” or “normal” phenotype. This “vascular normalization” is characterized by attenuation of hyperpermeability, increased vascular pericyte coverage, a more normal basement membrane, and a resultant reduction in tumor hypoxia and interstitial fluid pressure. These in turn can lead to an improvement in the metabolic profile of the tumor microenvironment, the delivery and efficacy of exogenously administered therapeutics, the efficacy of radiotherapy and of effector immune cells, and a reduction in number of metastatic cells shed by tumors into circulation in mice. These findings are consistent with data from clinical trials of anti-VEGF agents in patients with various solid tumors. More recently, genetic and pharmacological approaches have begun to unravel some other key regulators of vascular normalization such as proteins that regulate tissue oxygen sensing (PHD2) and vessel maturation (PDGFRβ, RGS5, Ang1/2, TGF-β). Here, we review the pathophysiology of tumor angiogenesis, the molecular underpinnings and functional consequences of vascular normalization, and the implications for treatment of cancer and nonmalignant diseases.

scholarly journals Review on Recent Trials Evaluating the Effect of Intravitreal Injections of Anti-VEGF Agents on the Macular Perfusion of Diabetic Patients with Diabetic Macular Edema

2020 ◽  
Vol 15 (3) ◽  
pp. 188-198
Author(s):  
Ayman G. Elnahry ◽  
Ahmed A. Abdel-Kader ◽  
Ahmed E. Habib ◽  
Gehad A. Elnahry ◽  
Karim A. Raafat ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Macular Edema ◽  
Diabetic Macular Edema ◽  
Vision Loss ◽  
Case Series ◽  
Diabetic Patients ◽  
Long Term Effects ◽  
Randomized Controlled Clinical Trials ◽  
Randomized Controlled ◽  
Anti Vegf

Background: Diabetic macular edema (DME) is a major cause of vision loss in diabetics worldwide. Anti-vascular endothelial growth factor (anti-VEGF) agents have become the mainstay of treatment of vision loss due to DME. Long-term effects of these agents on the macular perfusion (MP) are a current concern. Objective: To review recently published studies that evaluated the effect of intravitreal injection of anti-VEGF agents on the MP of diabetics with DME. Methods: Different databases were searched including PubMed, Medline, Ovid, Science Direct, and Google Scholar for relevant studies published between 2010 and 2019. All studies found were compared regarding methodology and results and included in this review. Some studies relating to retinal perfusion in general and not strictly MP were also included for comprehensiveness. Results: Several studies utilizing different anti-VEGF agents were identified. All the large randomized controlled clinical trials identified utilized primarily fluorescein angiography (FA) and human graders and found generally no worsening of MP associated with anti-VEGF agents use in diabetic patients with DME. Some of these studies, however, depended on post-hoc analysis. Several more recent, but smaller case series, have utilized the relatively new and non-invasive optical coherence tomography angiography (OCTA) in this evaluation and found more conflicting results. Conclusion: The large clinical trials recently performed depended mainly on FA in the analysis of MP changes following injections and generally found no worsening of MP. More recently, smaller case series have utilized OCTA in this analysis, yielding more conflicting results. Large randomized controlled trials using OCTA are thus needed.

Association between elevated blood pressure and clinical response in patients treated with anti-vascular endothelial growth factor (anti-VEGF) therapy in phase I clinical trials.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e13506-e13506
Author(s):  
Mehmet Asim Bilen ◽  
Aung Naing ◽  
David S. Hong ◽  
Gerald Steven Falchook ◽  
Siqing Fu ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Clinical Trials ◽  
Clinical Response ◽  
Prognostic Indicator ◽  
Median Number ◽  
Elevated Blood Pressure ◽  
Elevated Blood ◽  
Phase I Clinical Trials ◽  
Anti Vegf ◽  
Significant Difference

e13506 Background: Relationship between elevated blood pressure and clinical response in patients with advanced cancers treated with anti-VEGF treatment was evaluated. Methods: We performed an analysis of 438 consecutive patients from 19 clinical trials treated with therapy that included an anti-VEGF agent starting January, 2006. Clinical response was determined by RECIST 1.0. Blood pressures (BP) were scored as shown in Table. BP scores were calculated from an average mean BP of all BP readings for each patient, taken at each visit, and then divided into time points: baseline, 4, 8 and 12 months. Other factor included number of medication. Scores at each time point were compared to baseline value and divided into: increasing, decreasing and stable. Chi-square was used to correlate increased BP scores with clinical response. Additional analysis was also done by using CTCAE v4.02 for grading of BP. Results: The median age was 57 years (13 to 88) and 54% were male; 10% of patients received more than one anti-VEGF therapy. The median number of anti-VEGF therapies was 2 (1 to 3). Within the first four months, 52% of patients who achieved partial response (PR) had increased BP scores from baseline compared to 18% of those with progressive disease (PD) and 25% of those with stable disease (SD) (p <0.0001) (CTCAE; p=0.004) but there was no difference between SD and PD (p = 0.11) (CTCAE; p=0.31). The elevation in BP scores was significantly higher in the PR+SD group (31%) compared to PD group (18%) within 4 months (p=0.008) (CTCAE; p=0.07). There is a significant difference in increased BP scores among PR to SD groups within 8 months and 12 months (p=0.04 and p=0.028) (CTCAE; p=0.04 and p=0.107). Conclusions: Increasing BP scores is a positive prognostic indicator for favorable clinical response in patients who received anti-VEGF treatment. [Table: see text]

Bevacizumab: A Treatment Option for Recurrent Glioblastoma Multiforme

2008 ◽  
Vol 42 (10) ◽  
pp. 1486-1490 ◽  
Author(s):  
Larry W Buie ◽  
John M Valgus
Keyword(s):  
Clinical Trials ◽  
Growth Factor ◽  
Glioblastoma Multiforme ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Data Sources ◽  
Recurrent Glioblastoma Multiforme ◽  
Free Survival ◽  
Anti Vegf ◽  
Recurrent Gbm

Objective: To review the available literature evaluating the effect of bevacizumab on progression-free survival when used in combination with irinotecan for recurrent glioblastoma multiforme (GBM). Data Sources: Searches of MEDLINE (1966-June 2008), the Cochrane Library. and International Pharmaceutical Abstracts (1970-June 2008) were conducted using the terms bevacizumab. irinotecan, and glioblastoma multiforme. Study Selection And Data Extraction: The search was limited to studies conducted in humans. All articles identified trom the data sources were evaluated. All clinical trials evaluating the efficacy and safety of bevacizumab in the treatment of recurrent GBM were included in the review. Data Synthesis: Hypoxia, mutagenesis, and the secretion of various growth (actors can all lead to production of vascular endothelial growth factor (VEGF), a proangiogenic growth factor, and angiogenesis in GBM. Neoplastic progression is dependent on angiogenesis, and anti-VEGF therapy has been successful in multiple disease states. However, there are currently no available anti-VEGF therapies approved tor treatment of GBM. Bevacizumab is a humanized monoclonal antibody that binds to and inhibits the activity of VEGF. When compared with data from clinical trials that use single chemotherapeutic agents in recurrent GBM, the addition of bevacizumab to cytotoxic chemotherapy, such as irinotecan, appears to improve progression-Iree survival in patients progressing on the standard of care, with a 6-month progression-free survival rate of 46%. Bevacizumab is well tolerated by most patients, with modest risk (11% tn Phase 2 trials) of venous thromboembolism. Conclusions: Although the combination of bevacizumab and irinotecan is producing positive results in patients with recurrent GBM, larger, randomized clinical trials need to be performed to determine the magnitude of the benefit from bevacizumab. Bevacizumab administered biweekly at a dose of 10 mg/kg in combination with irinotecan may improve progression-free survival.

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