Evaluation of Vascular Endothelial Growth Factor (VEGF) and Thrombospondin-1 as Biomarkers of Metronomic Chemotherapy in Progressive Pediatric Solid Malignancies

Abstract

Objectives We compared Vascular Endothelial Growth factor (VEGF) and Thrombospondin-1 between patients with progressive paediatric malignancies randomized to metronomic chemotherapy versus placebo to determine their role as biomarker. Methods In this double-blinded, placebo-controlled randomized study of 108 progressive pediatric malignancies, serum VEGF and thrombospondin-1 levels were evaluated using ELISA at baseline, A2 (week-9 or earlier if progressed) and A3 (week-18 or earlier if progressed). Results Mean VEGF and thrombospondin-1 at baseline, A2 and A3 and the change from baseline to A2 were not different between two groups. In metronomic arm, responders (those completing 3 cycles) had significantly lower mean (SD) baseline VEGF levels [659.7(362.1) vs 1143.9 (622.0) µg/mL] (P=0.002) and significant decrease in thrombospondin-1 from baseline to A2 [−4.43(8.0) µg/mL vs 1.7(11.3) µg/mL] (P=0.04), as compared to non-responders. Similar changes were not observed in responders on placebo arm. No consistent trend of these biomarkers was observed. Conclusions VEGF and thrombospondin-1 are not reliable biomarkers for response to metronomic chemotherapy.