scholarly journals BEST: A Randomized Phase II Study of Vascular Endothelial Growth Factor, RAF Kinase, and Mammalian Target of Rapamycin Combination Targeted Therapy With Bevacizumab, Sorafenib, and Temsirolimus in Advanced Renal Cell Carcinoma—A Trial of the ECOG–ACRIN Cancer Research Group (E2804)

2015 ◽  
Vol 33 (21) ◽  
pp. 2384-2391 ◽  
Author(s):  
Keith T. Flaherty ◽  
Judith B. Manola ◽  
Michael Pins ◽  
David F. McDermott ◽  
Michael B. Atkins ◽  
...  

Purpose On the basis of evidence that resistance to vascular endothelial growth factor (VEGF) receptor inhibition is caused by hypoxia-driven residual VEGF and other proangiogenic factors, combinations of agents from these classes were hypothesized to improve treatment outcomes relative to single-agent VEGF pathway blockade. Patients and Methods A total of 361 patients with metastatic clear cell renal cell carcinoma were randomly assigned equally to arm A (bevacizumab monotherapy 10 mg/kg intravenously [IV] every 2 weeks), B (bevacizumab 10 mg/kg IV every 2 weeks and temsirolimus 25 mg IV every week), C (bevacizumab 5 mg/kg IV every 2 weeks and sorafenib 200 mg orally twice daily on days 1 to 5, 8 to 12, 15 to 19, and 22 to 26), or D (sorafenib 200 mg twice daily and temsirolimus 25 mg IV weekly). Progression-free survival was the primary end point. Results Among 331 eligible treated patients, median PFS was 7.5 months for bevacizumab alone (90% CI, 5.8 to 10.8 months), 7.6 months for bevacizumab plus temsirolimus (90% CI, 6.7 to 9.2 months), 9.2 months for bevacizumab plus sorafenib (90% CI, 7.5 to 11.4 months), and 7.4 months for sorafenib plus temsirolimus (90% CI, 5.6 to 7.9 months). Hazard ratios from stratified Cox proportional hazards models were 1.01, 0.89, and 1.07 (with respective P values of .95, .49, and .68) for the three combinations, respectively, compared with bevacizumab alone. Adverse events did not differ significantly among treatment arms. Conclusion The activity of sorafenib, temsirolimus, and bevacizumab administered in doublet combinations did not significantly improve median progression-free survival in comparison with bevacizumab monotherapy.

2007 ◽  
Vol 25 (1) ◽  
pp. 59-72 ◽  
Author(s):  
Christoph W. M. Reuter ◽  
Michael A. Morgan ◽  
Viktor Grünwald ◽  
Thomas R. W. Herrmann ◽  
Martin Burchardt ◽  
...  

2017 ◽  
Vol 5 (2) ◽  
pp. 167-172 ◽  
Author(s):  
Fahredin Veselaj ◽  
Suzana Manxhuka-Kerliu ◽  
Arber Neziri ◽  
Labinot Shahini ◽  
Shefki Xharra ◽  
...  

BACKGROUND: Clear cell renal cell carcinoma (CCRCC) is the most predominant renal tumour with unpredictable tumour behaviour. The aim of the study is to investigate the prognostic value of vascular endothelial growth factor A (VEGF-A) expression in CCRCC and to correlate it with other histological parameters as well as with patient's survival.MATERIAL AND METHODS: Tumour blocks were taken from 40 patients with histopathology diagnosis of CCRCC and tissue block from 20 normal kidneys as a control group were examined using the immuno-histochemical staining for VEGF-A.RESULTS: The VEGF A expression in CCRCC was significantly higher than in the normal kidney tissues (U’ = 720, P < 0.0001). VEGF A expression values in CCRCC were positively correlated with Disease Free Survival (r = 0.335, P = 0.034) and the tumor necrosis degree (r = 0.181, P = 0.262). VEGF-A expression values in CCRCC did not correlate with CD 31 expression (r = -0.09, P = 0.549), and Progression Free Survival (r = -0.07, P = 0.838). VEGF A expression values in CCRCC were negatively correlated with the tumor nuclear grade (r = -0.161, P = 0.318); the pathological tumor stage (r = -0.371, P = 0.018); the tumor size (r = -0.361, P = 0.022); the degree of tumor hemorrhage (r = -0.235, P = 0.143); and Cancer Specific Survival   (r = -0.207, P = 0.713).CONCLUSIONS: VEGF-A expression can be used to stratify advanced and metastatic CCRCC patients into low-benefit and high-benefit groups. Based on this study outcome it would be useful to perform IHC staining for VEGF-A expression in all patients with advanced and metastatic CCRCC.


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