Changes in Circulating VEGF Levels in Relation to Clinical Response during Chemotherapy for Metastatic Cancer

Abstract

Abnormally high blood levels of vascular endothelial growth factor (VEGF) appear to be associated with a poor prognosis in advanced cancer, probably as a consequence of its angiogenic and immunosuppressive effects. The prognostic significance of changes in VEGF secretion during cancer chemotherapy is still unknown. This study aimed to investigate the relation between VEGF variations and therapeutic results during chemotherapy in advanced malignancies. The study included 90 metastatic cancer patients, 59 with non-small cell lung cancer and 31 with colorectal carcinoma. Chemotherapy consisted of cisplatin plus etoposide for NSCLC and camptothecin for colorectal cancer. Abnormally high (> 2 SD with respect to values in healthy controls) pretreatment VEGF levels were found in 38/90 (42%) patients. The percentage of non-progressive disease in response to chemotherapy was significantly higher in patients with normal levels of VEGF prior to therapy than in those with elevated pretreatment values of VEGF (10/32 vs 4/27; p < 0.05). Moreover, the percentage of VEGF level normalization during chemotherapy was significantly higher in patients with objective tumor response or stable disease than in progressing patients (10/18 vs 0/20; p < 0.001). Finally, among patients with tumor response or disease stabilization, the one-year survival rate was significantly higher in patients with chemotherapy-induced normalization of VEGF than in those with persistently high VEGF blood levels (9/10 vs 3/8; p < 0.05). These results suggest that changes in VEGF levels during chemotherapy may represent a useful biomarker to predict the effect of chemotherapy in terms of tumor response and survival in patients with metastatic solid neoplasms.

Emerging Prognostic Biomarkers in Non Small Cell Lung Cancer Patients:Impact of Treatment with Nimesulide (COX-2 Inhibitor) Combined with Chemotherapy

“…These results agree with many authors [5,6,[12][13][14][15][16][17]. Vascular endothelial growth factor is the most potent and specific endothelial cell mitogen.…”

“…This is consistent with the study of Yuan et al [30] who reported increased VEGF-mRNA expression in adenocarcinoma lung tissues in comparison to other types, and attributed this to the high metastatic potential of adenocarcinoma [31].…”

“…The percentage of responders was 60% with a response rate of 53% after chemotherapy only and 69% after the combined therapy. These results are in harmony with many reports suggesting that the decrease in serum VEGF levels may predict the improvement of angiogenesis and tumor response which correlate with the survival of the patients [31,32]. In contrast, abnormally unchanged high VEGF levels appear to be associated with poor prognosis [31] and worse survival rate [3].…”

“…Vascular endothelial growth factor is the most potent and specific endothelial cell mitogen. It promotes vascularization, vascular permeability, and growth of primary tumour and provides a pathway for migrating tumour cells to gain access to the systemic circulation [6][7][8][9][10][11][12][13][14][15][16][17][18]. Interestingly, in this study, 3 patients developed pleural effusion and this may explain the strong role of VEGF in inducing vascular hyperpermiability which is implicated also in lymphatic spread and in turn patient's prognosis [19][20].…”

“…However, even in those resistant cases, the observed increased levels of many biomarkers may predict a slow response to the treatment. Lissoni et al [14] observed that the one year survival rate was significantly higher in patients with treatment-induced normalization of VEGF than in those with persistently high VEGF levels. The anti-angiogenic agents as a treatment modality in NSCLC act to prune and normalize the vascular supply that is typically aberrant in tumors, thus, inhibiting VEGF can counter tumor resistance to chemotherapy, radiotherapy and improve prospects for such patients [10,33].…”