A phase II study with antioxidants, both in the diet and supplemented, pharmaconutritional support, progestagen, and anti-cyclooxygenase-2 showing efficacy and safety in patients with cancer-related anorexia/cachexia and oxidative stress
In an open early-phase II study involving 44 patients with advanced cancer, adherence to a regimen including high amounts of dietary and supplementary antioxidants was found to increase body weight, lean body mass, and appetite, decrease proinflammatory cytokines (IL-6 and TNF-alpha), and improve quality of life, over a period of 4 months. Of the 44 patients who began the study, 39 completed the treatment and were assessed. Subjects selected for the study were advanced cancer patients with anorexia (loss of appetite), cachexia, and oxidative stress. For a period of 4 months, subjects adhered to a regimen consisting of dietary therapy, antioxidant supplementation therapy, and pharmaconutritional therapy. Dietary therapy consisted of 400 mg/day polyphenols. Antioxidant supplementation included 300 mg/day alpha-lipoic acid, 2.7 g/day carbocysteine lysine salt, 400 mg/day vitamin E, 30,000 IU/day vitamin A, and 500 mg/day vitamin C. Pharmaconutritional support included 500 mg/day medroxyprogesterone acetate, 200 mg/day selective cyclooxygenase-2 inhibitor celecoxib, along with omega-3 polyunsaturated fatty acids (eicosapentaenoic acid and docosahexaenoic acid). Safety and efficacy of this integrated treatment were assessed via clinical, nutritional, laboratory, and quality of life findings. After 4 months of treatment, body weight, lean body mass, and appetite increased significantly from baseline. In addition, levels of proinflammatory cytokines, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) decreased. A negative relationship was found between lean body mass and IL-6 changes. Furthermore, quality of life of the patients improved markedly. By the end of the study, 22 of the 39 patients were "responders" or "high responders." These results suggest that an integrated program including high amounts of antioxidants in the diet and through oral supplementation may be safe and effective in improving symptoms of low appetite, weight loss and diminished quality of life in patients with advanced stages of cancer. Based on these findings, a randomized, phase III study is warranted.