Reactive oxygen species, antioxidant mechanisms, and serum cytokine levels in cancer patients: impact of an antioxidant treatment

Objective: It has not been well established whether the oxidative stress found in cancer patients results from an increased production of oxidants in the body or from a failure of physiological antioxidant systems. To further investigate this question, we have assessed the blood levels of reactive oxygen species as a marker of free radicals producing oxidative stress and the most relevant of the physiological body enzymes counteracting reactive oxygen species, namely glutathione peroxidase and superoxide dismutase. We also investigated serum levels of proinflammatory cytokines and IL-2. All of these parameters were studied in relation to the most important clinical index of disease progression - namely, the Eastern Cooperative Oncology Group (ECOG) Performance Status (PS). We also tested the reducing ability of different antioxidant agents on reactive oxygen species levels by measuring the increase in glutathione peroxidase activity and the reduction of serum levels of IL-6 and TNF-α. Patients and Methods: We carried out an open nonrandomized study on 28 advanced stage cancer patients (stage III, 10.7% and stage IV, 89.3%) with tumors at different sites. The patients were divided into 5 groups, and a different antioxidant treatment was administered to each group. The antioxidants were alpha lipoic acid 200 mg/day orally; N-acetylcysteine 1800 mg/day i.v. or carboxycysteine-lysine salt 2.7 g/day orally; amifostine 375 mg/day i.v.; reduced glutathione 600 mg/day i.v.; and a combination of vitamin A 30,000 IU/day orally, vitamin E 70 mg/day orally, and vitamin C 500 mg/day orally. The antioxidant treatment was administered for 10 consecutive days. Results: We found that all but one of the antioxidants tested were effective in reducing reactive oxygen species levels, and two of them (cysteine- containing compounds and amifostine) had the additional effect of increasing glutathione peroxidase activity. Comprehensively, the antioxidant treatment was found to have an effect on both reactive oxygen species levels and glutathione peroxidase activity. The antioxidant treatment also reduced the serum levels of IL-6 and TNF-α. Patients in both ECOG PS 0-1 and ECOG PS 2-3 responded to antioxidant treatment.