Antioxidant stimulation as the adaptation mechanism in patients with metastatic urothelial cancers (MUC) treated with gemcitabine and cisplatin (GC).

Abstract

281 Background: The role of oxidative stress inpatients with MUC treated with GC is unknown. The objective of this ongoing study is to determinate plasma antioxidants, lipid peroxidation, and lipids in pts. with MUC before and after GC treatment, and to compare them with control. Methods: From May 2010 – January 2012, 42 MUC patients were enrolled into this study. The median of age was 65 years (range 44–81), median of metastasis sites was 2 (range 1–7). All patients were treated with gemcitabine 1000 mg/m2 i.v. days 1 and 8 with cisplatin 75 mg/m2 i.v. day 1, the new cycle of treatment started on day 22. Plasma samples were collected before and after 3 cycles of chemotherapy with GC. The control consisted of 22 subjects without cancer with age median 61 years (range 39–66). Results: In MUC patients, plasma γ-tocopherol before treatment were significantly lower (1.77±0.70 vs 2.13±0.70 μmol/L, P<0.04) and plasma TBARS higher vs control (5.76±1.32 vs 4.51±0.56 μmol/L, P<0.001). When compared baseline plasma levels to values after 3 cycles of GC, significant changes were noticed: γ-tocopherol (1.77±0.70 vs 2.29±1.14 μmol/L, P<0.04), α-tocopherol (24.23±5.14 vs 29.25±6.24 μmol/L, P<0.003), CoQ10-TOTAL (0.43±0.15 vs 0.56±0.16 μmol/L, P=0.003). TBARS concentrations were significantly decreased (5.76±1.32 vs 4.85±1.08 μmol/L, P=0.01). The concentrations of plasma lipids after GC were increased: Cholesterol (4.61±0.99 vs 5.47±1.21 mmol/L, P<0.004), TAG (1.30±0.65 vs 1.74±0.81 mmol/L, P<0.02), LDL cholesterol (2.94±0.73 vs 3.46±0.86 mmol/L, P<0.02), VLDL cholesterol (0.59±0.30 vs 0.81±0.37 mmol/L, P<0.02), and HDL cholesterol (1.08±0.39 vs 1.24±0.43 mmol/L, NS). Conclusions: GC in patients with MUC stimulated antioxidant defence system, increased plasma lipids, and decreased lipid peroxidation. The antioxidant stimulation might be one of the adaptation mechanisms that protect organism and might prevent or reduce chemotherapy side-effects. Acknowledgement: Study is supported by VEGA 1/0614/12 and Ministry of Health, Slovakia, grant 2007/29-UK-06.