Combination Therapy with Low Copper Diet, Penicillamine and Gamma Knife Radiosurgery Reduces VEGF and IL-8 In Patients with Recurrent Glioblastoma

Purpose: Vascular Endothelial Growth Factor (VEGF) and interleukin-8 (IL-8) appear important in tumor growth. In this study, we have investigated the effect of copper reduction along with gamma knife radiosurgery on IL-8 and VEGF in patients with recurrent glioblastoma multiforme (GBM). Materials and Methods: In a 3-month randomized clinical trial, patients with recurrent GBM were allocated randomly between intervention and placebo groups. Radiosurgery was performed for both groups (Reference dose: 16-18 Gray, in one fraction). The intervention group received low copper diet and penicillamine while the patients in the placebo group continued with their usual diet. VEGF and IL-8 were measured at baseline and the end of intervention. Results: VEGF in intervention group significantly reduced compared to placebo group (Mean ± SD, 4.5±1.91 vs. 7.8±3.21; P<0.001). IL-8 in intervention group decreased compared to placebo group but not significant (2.7±1.91 vs. 3.2±3.20; P=0.49). We also detected a significant positive correlation between serum copper and VEGF (r=0.57; P<0.05) and a negative correlation between KPS and serum copper. Discussion: Our results could reflect that low copper diet and penicillamine may decrease serum VEGF in patients who underwent gamma knife radiosurgery for recurrent glioblastoma multiforme.