Significance Of Serum VEGF In Lung Cancer And Angiogenic Inhibitors In The Treatment Of Advanced Non-Small Cell Lung Cancer

Lung cancer is the leading cause of cancer-related deaths, and the incidence is still increasing. More than 50% of lung cancer patients who undergo surgery will eventually experience local relapse or distant metastasis. The high metastatic potential of lung cancer may be due to active angiogenesis of the tumors, in which VEGF, the most potent angiogenic factor, plays an important role. VEGF is also a key target for antiangiogenic inhibitors.We measured serum VEGF levels using enzyme-linked immunosorbent assay in 74 patients with lung cancer and 20 healthy subjects. Compared to the controls, the VEGF levels of patients with lung cancer were significantly higher and the median concentrations of VEGF were 58.9pg/ml and 208.5pg/ml, respectively. As a tumor marker in lung cancer, the diagnostic sensitivity of VEGF was 25.7%. The pre-treatment VEGF levels were much higher in the inoperable and metastatic patients than the operable and non-metastatic patients. The pre-treatment VEGF concentrations were not associated with the gender, age, histology, smoke history and chemotherapy efficacy. But there was a statistic difference trend between pre-treatment VEGF levels and tumor differentiation (p=0.070). Compared to pre-treatment, the VEGF levels were significantly decreased in patients with NSCLC after radical resection or the patients with SCLC after two cycles of chemotherapy(p＜0.05). However, it didn't change significantly in patients with advanced NSCLC after the first- or second-line chemotherapy. Chemotherapy combined angiogenic inhibitors (AIs) for the second-line treatment of advanced NSCLC had a better response rates and decreased VEGF levels more significantly than chemotherapy alone. The response rates were 31.8% and 8.5%, respectively. Chemotherapy combined AIs was a single factor that might influence the response rate by multivariate logistic regression analysis. Univariate analysis showed that chemotherapy combined AIs might significantly prolong TTP (5.0 months vs 2.5 months, p=0.045), but no influence on MST (12.0 months vs 8.0 months p=0.103). Combination treatment also had a wall tolerate toxicity. However, Cox regression model predicted that efficacy of second-line chemotherapy and patients' gender were the independent survival prognostic factors in the second-line treatment of advanced NSCLC patients who have a good performance status.