Increases in circulating VEGF levels during COX-2 inhibitor treatment in breast cancer patients.

Cyclooxygenase-2 (COX-2) inhibitors are being tried in clinics for cancer treatment. One of the mechanism by which COX-2 inhibitors suppress cancer progression is suggested to be inhibition of angiogenesis. To investigate how COX-2 inhibitors affect regulation of angiogenic factors, we studied alterations in VEGF levels in sera and plasma during COX-2 inhibitor treatment in breast cancer patients. Serum and plasma VEGF levels were monitored in 48 patients treated with the COX-2 inhibitor celecoxib together with 5-FU, epirubicine, cyclophosphamide (FEC). Serum VEGF levels showed decreases on day 3 of the first cycle (P<0.0001), followed by increases after 3 weeks (P<0.0001). Plasma VEGF levels did not show decreases on day 3 but showed increases after 3 weeks (P<0.05). The increases of VEGF levels in sera and plasma continued until the next cycle of the treatment. In patients treated with FEC alone (without celecoxib) did not show increases in serum VEGF levels during the treatment. Our data showed that treatment with COX-2 inhibitors decreased serum VEGF levels at an early time and increased VEGF levels in serum and plasma at a late time in breast cancer patients. Further studies are necessary to elucidate how COX-2 inhibitors regulate production of VEGF in different cells and different tissues in cancer patients.