scholarly journals Association of Vascular Endothelial Growth Factor and Vascular Endothelial Growth Factor Receptor-2 Genetic Polymorphisms With Outcome in a Trial of Paclitaxel Compared With Paclitaxel Plus Bevacizumab in Advanced Breast Cancer: ECOG 2100

2008 ◽  
Vol 26 (28) ◽  
pp. 4672-4678 ◽  
Author(s):  
Bryan P. Schneider ◽  
Molin Wang ◽  
Milan Radovich ◽  
George W. Sledge ◽  
Sunil Badve ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Metastatic Breast Cancer ◽  
Growth Factor ◽  
Metastatic Breast ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Vascular Endothelial ◽  
Grade 3 ◽  
Endothelial Growth Factor

Purpose No biomarkers have been identified to predict outcome with the use of an antiangiogenesis agent for cancer. Vascular endothelial growth factor (VEGF) genetic variability has been associated with altered risk of breast cancer and variable promoter activity. Therefore, we evaluated the association of VEGF genotype with efficacy and toxicity in E2100, a phase III study comparing paclitaxel versus paclitaxel plus bevacizumab as initial chemotherapy for metastatic breast cancer. Patients and Methods DNA was extracted from tumor blocks of patients from E2100. Three hundred sixty-three samples were available to evaluate associations between genotype and outcome. Genotyping was performed for selected polymorphisms in VEGF and VEGF receptor 2. Testing for associations between each polymorphism and efficacy and toxicity was performed. Results The VEGF-2578 AA genotype was associated with a superior median overall survival (OS) in the combination arm when compared with the alternate genotypes combined (hazard ratio = 0.58; 95% CI, 0.36 to 0.93; P = .023). The VEGF-1154 A allele also demonstrated a superior median OS with an additive effect of each active allele in the combination arm but not the control arm (hazard ratio = 0.62; 95% CI, 0.46 to 0.83; P = .001). Two additional genotypes, VEGF-634 CC and VEGF-1498 TT, were associated with significantly less grade 3 or 4 hypertension in the combination arm when compared with the alternate genotypes combined (P = .005 and P = .022, respectively). Conclusion Our data support an association between VEGF genotype and median OS as well as grade 3 or 4 hypertension when using bevacizumab in metastatic breast cancer.

Phase I/II Trial of Metronomic Chemotherapy With Daily Dalteparin and Cyclophosphamide, Twice-Weekly Methotrexate, and Daily Prednisone As Therapy for Metastatic Breast Cancer Using Vascular Endothelial Growth Factor and Soluble Vascular Endothelial Growth Factor Receptor Levels As Markers of Response

2010 ◽  
Vol 28 (5) ◽  
pp. 723-730 ◽  
Author(s):  
Nan Soon Wong ◽  
Robert A. Buckman ◽  
Mark Clemons ◽  
Shailendra Verma ◽  
Susan Dent ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Metastatic Breast Cancer ◽  
Growth Factor ◽  
Metastatic Breast ◽  
Metronomic Chemotherapy ◽  
Vascular Endothelial ◽  
Grade 3 ◽  
Daily Prednisone ◽  
Endothelial Growth Factor

Purpose Preclinical studies indicate that metronomic chemotherapy is antiangiogenic and synergistic with other antiangiogenic agents. We designed a phase I/II study to evaluate the safety and activity of adding dalteparin and prednisone to metronomic cyclophosphamide and methotrexate in women with measurable metastatic breast cancer (MBC). Patients and Methods Patients received daily dalteparin and oral cyclophosphamide, twice-weekly methotrexate, and daily prednisone (dalCMP). The primary study end point was clinical benefit rate (CBR), a combination of complete response (CR), partial response (PR), and prolonged stable disease for ≥ 24 weeks (pSD). Secondary end points included time to progression (TTP), duration of response, and overall survival (OS). Biomarker response to treatment was assessed by using plasma vascular endothelial growth factor (VEGF) and soluble VEGF receptors (sVEGFRs) –1 and –2. Results Forty-one eligible patients were accrued. Sixteen (39%) had no prior chemotherapy for MBC; 15 (37%) had two or more chemotherapy regimens for MBC. Toxicities were minimal except for transient grade 3 elevation of liver transaminases in 11 patients (27%) and grade 3 vomiting in one patient (2%). One patient (2%) had CR, six (15%) had PR, and three (7%) had pSD, for a CBR of 10 (24%) of 41 patients. Median TTP was 10 weeks (95% CI, 8 to 17 weeks), and median OS was 48 weeks (95% CI, 32 to 79 weeks). VEGF levels decreased but not significantly, whereas sVEGFR-1 and -2 levels increased significantly after 2 weeks of therapy. There was no correlation between response and VEGF, sVEGFR-1, or sVEGFR-2 levels. Conclusion Metronomic dalCMP is safe, well tolerated, and clinically active in MBC.

Chemotherapy and Angiogenesis in Advanced Cancer: Vascular Endothelial Growth Factor (VEGF) Decline as Predictor of Disease Control during Taxol Therapy in Metastatic Breast Cancer

2000 ◽  
Vol 15 (4) ◽  
pp. 308-311 ◽  
Author(s):  
P. Lissoni ◽  
E. Fugamalli ◽  
F. Malugani ◽  
A. Ardizzoia ◽  
S. Secondino ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Metastatic Breast Cancer ◽  
Growth Factor ◽  
Cancer Patients ◽  
Advanced Cancer ◽  
Metastatic Breast ◽  
Vascular Endothelial ◽  
Preliminary Study ◽  
Endothelial Growth Factor

Angiogenesis is essential for tumor growth. Since vascular endothelial growth factor (VEGF) represents the main angiogenic factor, the control of VEGF secretion could constitute the most important mechanism to achieve the inhibition of angiogenesis-related processes. High blood concentrations have been proven to correlate with poor prognosis in advanced cancer. In experimental conditions, chemotherapeutic agents such as taxol appeared to inhibit VEGF-induced angiogenesis, while at present there are no data about the influence of chemotherapy on VEGF secretion in cancer patients. This preliminary study was performed to evaluate the effect of taxol therapy on VEGF secretion in advanced cancer patients in relation to the clinical response. The study included 14 patients with metastatic breast cancer who were treated with taxol monochemotherapy (175 mg/m2 i.v. every 21 days for three cycles). Serum levels of VEGF were measured by ELISA in blood samples collected before therapy and at 21-day intervals. The clinical response consisted of partial response (PR) in three and stable disease (SD) in six patients, whereas the other five patients had progressive disease (PD). Abnormally high pre-treatment levels of VEGF were seen in 8/14 patients. VEGF mean values significantly decreased during taxol therapy in patients with PR or SD, whereas no decline was observed in patients with PD. Moreover, the percent of normalization or decline greater than 50% in VEGF levels was significantly higher in patients with PR or SD than in those with PD (5/9 vs. 0/5). This preliminary study would suggest that the efficacy of taxol therapy in metastatic breast cancer - at least in terms of disease stabilization - may be associated with a decrease in VEGF blood levels followed by potential inhibition of cancer-related neovascularization.

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