Research Opportunities for Vascular Endothelial Growth Factor Receptor and Ki67 Relative Percentage Co-reduction in Patients with Locally Advanced Rectal Cancer Treated with Neoadjuvant Therapy

2014 ◽  
Vol 26 (2) ◽  
pp. 122-123 ◽  
Author(s):  
C.V. Sole ◽  
F.A. Calvo
Keyword(s):  
Rectal Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Locally Advanced ◽  
Growth Factor Receptor ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Vascular Endothelial ◽  
Relative Percentage ◽  
Co Reduction ◽  
Endothelial Growth Factor

scholarly journals Efficacy, Safety, and Biomarkers of Neoadjuvant Bevacizumab, Radiation Therapy, and Fluorouracil in Rectal Cancer: A Multidisciplinary Phase II Study

2009 ◽  
Vol 27 (18) ◽  
pp. 3020-3026 ◽  
Author(s):  
Christopher G. Willett ◽  
Dan G. Duda ◽  
Emmanuelle di Tomaso ◽  
Yves Boucher ◽  
Marek Ancukiewicz ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Vascular Endothelial ◽  
External Beam Irradiation ◽  
Mean Size ◽  
Endothelial Growth Factor

Purpose To assess the safety and efficacy of neoadjuvant bevacizumab with standard chemoradiotherapy in locally advanced rectal cancer and explore biomarkers for response. Patients and Methods In a phase I/II study, 32 patients received four cycles of therapy consisting of: bevacizumab infusion (5 or 10 mg/kg) on day 1 of each cycle; fluorouracil infusion (225 mg/m2/24 hours) during cycles 2 to 4; external-beam irradiation (50.4 Gy in 28 fractions over 5.5 weeks); and surgery 7 to 10 weeks after completion of all therapies. We measured molecular, cellular, and physiologic biomarkers before treatment, during bevacizumab monotherapy, and during and after combination therapy. Results Tumors regressed from a mass with mean size of 5 cm (range, 3 to 12 cm) to an ulcer/scar with mean size of 2.4 cm (range, 0.7 to 6.0 cm) in all 32 patients. Histologic examination revealed either no cancer or varying numbers of scattered cancer cells in a bed of fibrosis at the primary site. This treatment resulted in an actuarial 5-year local control and overall survival of 100%. Actuarial 5-year disease-free survival was 75% and five patients developed metastases postsurgery. Bevacizumab with chemoradiotherapy showed acceptable toxicity. Bevacizumab decreased tumor interstitial fluid pressure and blood flow. Baseline plasma soluble vascular endothelial growth factor receptor 1 (sVEGFR1), plasma vascular endothelial growth factor (VEGF), placental-derived growth factor (PlGF), and interleukin 6 (IL-6) during treatment, and circulating endothelial cells (CECs) after treatment showed significant correlations with outcome. Conclusion Bevacizumab with chemoradiotherapy appears safe and active and yields promising survival results in locally advanced rectal cancer. Plasma VEGF, PlGF, sVEGFR1, and IL-6 and CECs should be further evaluated as candidate biomarkers of response for this regimen.

Docetaxel As Monotherapy or Combined With Ramucirumab or Icrucumab in Second-Line Treatment for Locally Advanced or Metastatic Urothelial Carcinoma: An Open-Label, Three-Arm, Randomized Controlled Phase II Trial

2016 ◽  
Vol 34 (13) ◽  
pp. 1500-1509 ◽  
Author(s):  
Daniel P. Petrylak ◽  
Scott T. Tagawa ◽  
Manish Kohli ◽  
Andrea Eisen ◽  
Christina Canil ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Urothelial Carcinoma ◽  
Locally Advanced ◽  
Growth Factor Receptor ◽  
Vascular Endothelial ◽  
Line Treatment ◽  
Second Line ◽  
Metastatic Urothelial Carcinoma ◽  
Endothelial Growth Factor

Purpose This trial assessed the efficacy and safety of docetaxel monotherapy or docetaxel in combination with ramucirumab (vascular endothelial growth factor receptor 2 antibody) or icrucumab (vascular endothelial growth factor receptor 1 antibody) after progression during or within 12 months of platinum-based regimens for patients with locally advanced or metastatic urothelial carcinoma. Patients and Methods Patients were randomly assigned (1:1:1) to receive docetaxel 75 mg/m2 intravenously (IV) on day 1 of a 3-week cycle (arm A), docetaxel 75 mg/m2 IV plus ramucirumab 10 mg/kg IV on day 1 of a 3-week cycle (arm B), or docetaxel 75 mg/m2 IV on day 1 plus icrucumab 12 mg/kg IV on days 1 and 8 of a 3-week cycle (arm C). Treatment continued until disease progression or unacceptable toxicity. The primary end point was investigator-assessed progression-free survival (PFS). Results A total of 140 patients were randomly assigned and treated in arms A (n = 45), B (n = 46), or C (n = 49). PFS was significantly longer in arm B compared with arm A (median, 5.4 months; 95% CI, 3.1 to 6.9 months v 2.8 months; 95% CI, 1.9 to 3.6 months; stratified hazard ratio, 0.389; 95% CI, 0.235 to 0.643; P = .0002). Arm C did not experience improved PFS compared with arm A (1.6 months; 95% CI, 1.4 to 2.9; stratified hazard ratio, 0.863; 95% CI, 0.550 to 1.357; P = .5053). The most common grade 3 or worse adverse events (arms A, B, and C) were neutropenia (36%, 33%, and 39%), fatigue (13%, 30%, and 20%), febrile neutropenia (13%, 17%, and 6.1%), and anemia (6.7%, 13%, and 14%, respectively). Conclusion The addition of ramucirumab to docetaxel met the prespecified efficacy end point for prolonging PFS in patients with locally advanced or metastatic urothelial carcinoma receiving second-line treatment and warrants further investigation in the phase III setting.

scholarly journals Methylation status of p16 and p14 genes in locally advanced rectal cancer: Potential clinical implication

2018 ◽  
Vol 70 (4) ◽  
pp. 681-690
Author(s):  
Bojana Kozik ◽  
Nikola Kokanov ◽  
Slavica Knezevic-Usaj ◽  
Ivan Nikolic ◽  
Radoslav Davidovic ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Overall Survival ◽  
Growth Factor ◽  
Methylation Status ◽  
Locally Advanced ◽  
Growth Factor Receptor ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Vegf Expression ◽  
Egfr Expression

Methylation of p16 and p14 genes is a common event in colorectal cancers; however, their exact role in the prediction of patients? outcome is unclear. We conducted this retrospective study to evaluate their potential predictive and/or prognostic roles. Methylation-specific PCR was used to examine the methylation status of p16 and p14 in pretherapeutic and preoperative biopsy specimens of 60 patients with locally advanced rectal cancer. The methylation status of the examined genes did not affect the response to preoperative chemoradiotherapy (CRT), recurrence rate and overall survival. However, patients with a simultaneous presence of either p16 or p14 methylation and high vascular endothelial growth factor (VEGF) expression showed a significantly worse response to CRT (p=0.005 and p=0.038, respectively). Moreover, patients with both p16 methylation and high VEGF expression had significantly shorter overall survival (p=0.010), while no such association was found in patients with p14 methylation and high VEGF expression. On the other hand, a subgroup of patients with p16 methylation and low VEGF and high epidermal growth factor receptor (EGFR) expression showed a significantly better response to CRT (p=0.024). The obtained results point to the importance of p16 and p14 methylation analyses in combination with VEGF and EGFR expression, aimed at better predicting treatment response and patient outcome.

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