Circulating Vascular Endothelial Growth Factor, C-reactive Protein and Urinary Neopterin Concentrations During dose-dense Chemotherapy

Angiogenesis plays a crucial role in tumor progression. Prominent among angiogenic factors is vascular endothelial growth factor (VEGF). VEGF is produced by cancer cells as well as by the cells infiltrating tumor stroma, mainly macrophages. Macrophage activation may be assessed by measuring serum or urinary neopterin. Systemic inflammatory response could be evaluated by measuring serum C-reactive protein concentrations. The aim of the present study was to examine the effect of a regimen combining dose dense combination of doxorubicin and cyclophosphamide with sequential weekly paclitaxel on plasma VEGF, urinary neopterin and serum C-reactive protein concentrations. Thirty-four female patients with histologically verified breast carcinoma treated with dose-dense regimen combining doxorubicin and cyclophosphamide with sequential weekly paclitaxel administration were studied. Plasma VEGF was measured by enzyme-linked immunosorbent assay. Urinary neopterin was determined by high performance liquid chromatography. Compared to baseline plasma VEGF was significantly decreased one week after the start of therapy. VEGF concentrations subsequently increased, but this increase was significant compared to baseline only at week 16. Urinary neopterin was significantly increased compared to baseline at every visit with the exception of visits 12 and 20 at which the significance was borderline. Serum C-reactive protein was increased compared to baseline only at visits 4, 6 and 8. A positive correlation was observed between plasma VEGF and serum C-reactive protein at baseline and at visits 5 and 19. Significant correlations were observed between serum C-reactive protein and urinary neopterin at visits 6, 7, 9, 11, 14, 15 and 17. In conclusion, only minor changes in plasma VEGF and serum C-reactive protein were observed during dose-dense chemotherapy. In contrast, urinary neopterin was increased throughout the course of treatment. Correlations between VEGF and C-reactive protein and between Creactive protein and urinary neopterin were observed only at some time points.