scholarly journals Safety of high-dose intravitreal triamcinolone acetonide as low-cost alternative to anti-vascular endothelial growth factor agents in lower-middle-income countries

2018 ◽  
Vol Volume 12 ◽  
pp. 2383-2391 ◽  
Author(s):  
Hammouda Hamdy Ghoraba ◽  
Mahmoud Leila ◽  
Sameh Mohamed Elgouhary ◽  
Emad Eldin Mohamed Elgemai ◽  
Haithem Mamon Abdelfattah ◽  
...  
2009 ◽  
Vol 27 (36) ◽  
pp. 6152-6159 ◽  
Author(s):  
Marlies H.G. Langenberg ◽  
Carla M.L. van Herpen ◽  
Johann De Bono ◽  
Jan H.M. Schellens ◽  
Clemens Unger ◽  
...  

Purpose Hypertension is a commonly reported adverse effect after administration of vascular endothelial growth factor (VEGF) inhibitors. Cediranib is a highly potent and selective VEGF signaling inhibitor of all three VEGFRs. This study prospectively investigated hypertension management to help minimize dose interruptions/reductions to maximize cediranib dose intensity. Patients and Methods Patients (n = 126) with advanced solid tumors were randomly assigned to one of four groups: cediranib 30 or 45 mg/d with or without antihypertensive prophylaxis. All patients developing hypertension on cediranib treatment were treated with a standardized, predefined hypertension management protocol. Results Cediranib was generally well tolerated, and all groups achieved high-dose intensities in the first 12 weeks (> 74% in all groups). Antihypertensive prophylaxis did not result in fewer dose reductions or interruptions. Increases in blood pressure, including moderate and severe readings of hypertension, were seen early in treatment in all groups and successfully managed. Severe hypertension occurred in one patient receiving prophylaxis versus 18 in the nonprophylaxis groups. Overall, there were nine partial responses, and 38 patients experienced stable disease ≥ 8 weeks. Conclusion To our knowledge, this is the first prospective investigation of hypertension management during administration of a VEGF signaling inhibitor. All four regimens were well tolerated with high-dose intensities and no strategy was clearly superior. The current cediranib hypertension management protocol appears to be effective in managing hypertension compared with previous cediranib studies where no plan was in place, and early recognition and treatment of hypertension is likely to reduce the number of severe hypertension events. This protocol is included in all ongoing cediranib clinical studies.


Endocrinology ◽  
2008 ◽  
Vol 149 (8) ◽  
pp. 3881-3889 ◽  
Author(s):  
Shameena Bake ◽  
Lijiang Ma ◽  
Farida Sohrabji

Estrogen and its receptors influence growth and differentiation by stimulating the production and secretion of growth factors. Our previous studies indicate an increased expression of estrogen receptor (ER)-α and decreased growth factor synthesis in the olfactory bulb of reproductive senescent female rats as compared with young animals. The present study tests the hypothesis that abnormal overexpression of ERα contributes to decreased growth factor synthesis. We developed the HeLa-Tet-On cell line stably transfected with ERα (HTERα) that expresses increasing amounts of ERα with increasing doses of doxycycline (Dox). Increasing doses of Dox had no effect on vascular endothelial growth factor (VEGF) secretion in HTERα cells. However, in the presence of 40 nm 17β-estradiol, VEGF secretion increased in low-dose Dox-exposed HTERα cultures, which was attenuated by the ERα antagonist, 1,3-Bis(4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy)phenol]1H-pyrazole dihydrochloride. However, at high-dose Dox and, consequently, high ERα levels, estradiol failed to increase VEGF. In the HeLa X6 cell line in which the Tet-On construct is upstream of an unrelated gene (Pitx2A), estradiol failed to induce VEGF at any Dox dose. Furthermore, in the HTERα cell line, estradiol selectively down-regulates phospho-ERK2 and phospho-Akt at high ERα expression. This study clearly demonstrates that the dose of receptor critically mediates estradiol’s ability to regulate growth factors and survival kinases. The present data also support the hypothesis that 17β-estradiol treatment to an ERα overexpressing system, such as the senescent brain, could reverse the normally observed beneficial effect of estrogen.


2009 ◽  
Vol 27 (16) ◽  
pp. 2645-2652 ◽  
Author(s):  
Marianna Sabatino ◽  
Seunghee Kim-Schulze ◽  
Monica C. Panelli ◽  
David Stroncek ◽  
Ena Wang ◽  
...  

Purpose High-dose interleukin-2 (IL-2) induces durable therapeutic responses in a small subset of patients with metastatic melanoma and renal cell carcinoma, but simple pretreatment predictors of response have not been identified. Patients and Methods To identify predictive biomarkers of clinical response, sera from patients treated with high-dose IL-2 were collected for analysis using a customized, multiplex antibody-targeted protein array platform that surveyed expression of soluble factors associated with tumor immunobiology. Soluble factors associated with clinical responses were analyzed using a multivariate permutation test, and survival outcomes were determined using Kaplan-Meier and log-rank tests. Results A training set from 10 patients identified 68 potentially relevant soluble factors that were then tested in an independent validation set of 49 patients. Class comparison revealed a cluster of 11 biomarkers that were associated with therapeutic outcome. Vascular endothelial growth factor (VEGF) and fibronectin were identified as independent predictors of response. In particular, high levels of these proteins were correlated with lack of clinical response and decreased overall survival. Conclusion Serum VEGF and fibronectin are easily measured pretreatment biomarkers that could serve to exclude patients unlikely to respond to IL-2 therapy.


2021 ◽  
Vol 8 (24) ◽  
pp. 2083-2088
Author(s):  
Pradeep Kumar Panigrahi ◽  
Suprava Das ◽  
Suchismita Mishra

BACKGROUND Macular oedema due to retinal vein occlusion can be refractory to treatment with anti-vascular endothelial growth factor agents in some patients. We wanted to evaluate the efficacy of single dose of intravitreal triamcinolone acetonide in the treatment of macular oedema due to retinal vein occlusion, which is refractory to anti-vascular endothelial growth factor agents. METHODS 32 patients with refractory macular oedema were included in this prospective, interventional, comparative study. 20 patients were included in the study group and received 4 mg / 0.1 ml of intravitreal triamcinolone acetonide. 12 patients in control group did not receive any treatment. Best corrected visual acuity (BCVA) and central foveal thickness (CFT) were assessed in each group at 1 week, 1 month, 2 months and 3 months following injection. RESULTS Mean BCVA in study group improved from 1.36 ± 0.33 logarithm of minimum angle of resolution (LogMAR) at baseline to 0.94 ± 0.49 LogMAR at the end of 3 months. Mean CFT at baseline and 3 months was 498.65 ± 90.64 and 331 ± 100.57 microns respectively in the study group. The mean baseline BCVA and CFT in the control group was 1.19 ± 0.43 LogMAR and 428.33 ± 101.75 microns respectively. Mean BCVA and CFT at the end of 3 months was 1.16 ± 0.45 LogMAR and 424.75 ± 98.75 microns respectively. Change in mean BCVA and CFT at baseline and at the end of 3 months was found to be statistically significant (P = 0.000) between the 2 groups. There was increase in macular oedema in the study patients after the 2nd month following injection leading to slight worsening of visual acuity. CONCLUSIONS Intravitreal triamcinolone acetonide is an option in the treatment of macular oedema due to retinal vein occlusion refractory to anti-vascular endothelial growth factor agents. However, the efficacy of a single injection is short lived. Multiple injections might be needed to maintain the visual gains. KEYWORDS Retinal Vein Occlusion, Macular Oedema, Refractory, Triamcinolone, Intravitreal


2004 ◽  
Vol 44 (4) ◽  
pp. 349-356 ◽  
Author(s):  
Hua Gao ◽  
Xiaoxi Qiao ◽  
Rui Gao ◽  
William F. Mieler ◽  
Alice R. McPherson ◽  
...  

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