Targeting Vascular Endothelial Growth Factor Pathway in First-Line Treatment of Metastatic Colorectal Cancer: State-of-the-Art and Future Perspectives in Clinical and Molecular Selection of Patients

2010 ◽  
Vol 999 (999) ◽  
pp. 1-9
Author(s):  
F. Loupakis ◽  
G. Bocci ◽  
G. Pasqualetti ◽  
L. Fornaro ◽  
L. Salvatore ◽  
...  
Keyword(s):  
State Of The Art ◽  
Vascular Endothelial ◽  
Line Treatment ◽  
Future Perspectives ◽  
First Line ◽  
Molecular Selection ◽  
Endothelial Growth Factor ◽  
Selection Of Patients ◽  
First Line Treatment ◽  
Selection Of

scholarly journals Vascular endothelial growth factor-A is an Immunohistochemical biomarker for the efficacy of bevacizumab-containing chemotherapy for duodenal and jejunal adenocarcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Takahiro Amano ◽  
Hideki Iijima ◽  
Shinichiro Shinzaki ◽  
Taku Tashiro ◽  
Shuko Iwatani ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Overall Survival ◽  
Progression Free Survival ◽  
Vascular Endothelial ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
Platinum Based Chemotherapy ◽  
Endothelial Growth Factor ◽  
First Line Treatment

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.

scholarly journals Vascular Endothelial Growth Factor-A is an Immunohistochemical Biomarker for the Efficacy of Bevacizumab-containing Chemotherapy for Duodenal and Jejunal Adenocarcinoma

2021 ◽  
Author(s):  
Takahiro Amano ◽  
Hideki Iijima ◽  
Shinichiro Shinzaki ◽  
Taku Tashiro ◽  
Shuko Iwatani ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Overall Survival ◽  
Progression Free Survival ◽  
Vascular Endothelial ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
Platinum Based Chemotherapy ◽  
Endothelial Growth Factor ◽  
First Line Treatment

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.

A Rational Sequencing of Anti-Angiogenic Agents as Second-Line Treatment Choice for mCRC Patients Progressing After a Bevacizumab-Based First Line

2020 ◽  
pp. 14-19
Author(s):  
Sara De Dosso
Keyword(s):  
Acquired Resistance ◽  
Predictive Biomarker ◽  
Cancer Therapies ◽  
Vascular Endothelial ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Vegf Pathway ◽  
Effective Choice ◽  
Endothelial Growth Factor

A large proportion of patients with metastatic colorectal cancer (mCRC) experience disease progression after first-line treatment with chemotherapy and bevacizumab, an anti-angiogenic agent, as a result of acquired resistance. However, blocking angiogenesis by targeted therapy towards the vascular endothelial growth factor (VEGF) pathway still forms an essential part of the second-line treatment strategy. Although three approved evidence-based choices for angiogenic agents (continuing treatment with bevacizumab, ramucirumab and aflibercept) are currently available in the second line, making the most effective choice is challenging due to the lack of studies directly comparing these agents. Moreover, despite huge investigational efforts, no predictive biomarker for anti-angiogenic cancer therapies could be identified so far.

Biweekly treatment with bevacizumab (BV) as 2nd line chemotherapy in patients with metastatic colorectal cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13561-13561
Author(s):  
G. F. Samelis ◽  
A. Areovimata ◽  
D. Adrachta ◽  
A. Palazi ◽  
V. Papagianni
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Lung Metastases ◽  
Vascular Endothelial ◽  
Line Treatment ◽  
First Line ◽  
Grade Ii ◽  
Metastatic Sites ◽  
Endothelial Growth Factor ◽  
Line Chemotherapy

13561 Background: Bevacizumab (BV), a monoclonal antibody directed against vascular endothelial growth factor, provides a survival advantage (15.6 to 20.3 months) when added to first-line chemotherapy for metastatic colorectal cancer (metastatic CRC). Only a few trials have been conducted using BV as 2nd line chemotherapy. Methods: Sixteen patients with metastatic CRC refractory to first-line chemotherapy (oxaliplatin or irinotecan-based regimen) were enrolled. All patients, after progressing in first-line treatment, received the following regimen: BV: 5 mg/Kg* in 1000ml water for injection in 90min IV infusion plus irinotecan 125mg/m2 IV in 500ml NIS in 60min plus folinic acid 30mg/m2 and 5-fluorouracil 500mg/m2 IV bolus infusion. The schedule was repeated every 2 weeks. Fourteen men and 2 women entered the study with PS 0–1, median age of 66 years (range: 48–85). 11 patients (68.7%) had liver metastases, 3 patients (18.75%) had lung metastases and 4 patients (25%) had local tumor recurrence. All 16 patients were eligible for the study and received in total 174 (mean 10.8, range: 6–20) cycles. Six out of 16 patients (12.5%) had more than 2 metastatic sites (liver and local recurrence). Results: Six patients had partial responses (PRs) (37.5%), 4 patients had stable disease (SD) (25%) and the rest of the patients progressed (37.5%). The time to progression (TTP) was 6.4 months (range: 4–8), and the median survival was 9 (range: 5–12) months. The toxicity was mild and no toxic death was reported. Grade II toxicities were the following: epistaxis 4 patients (25%), anaemia 5 patients (31%), leukopenia 3 patients (18.7%), granulocytopenia 2 patients (12.5%) and 1 patient developed jaundice due to bile-duct obstruction. Conclusions: The bi-weekly administration of BV, irinotecan, leucovorin and 5-fluororacil is acceptable as 2nd line treatment in patients with metastatic CRC, with an overall response rate (PRs) of 37.5%, and SD of 25%. The TTP and survival were 6.4 and 9 months respectively. The study is ongoing and we expect to enrol more patients. No significant financial relationships to disclose.

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