Cancer Anorexia/Cachexia Syndrome (CACS) and Oxidative Stress (OS) play a key role in the progression and outcome of neoplastic disease.On the basis of our previous studies we developed an innovative approach consisting of diet with high polyphenols content (400 mg), oral pharmaco-nutritional support enriched with n-3 PUFA (EPA, DHA) 2 cans (237 ml each)/day, medroxiprogesterone acetate 500 mg/day, antioxidants (alpha lipoic acid 300 mg/day | carbocysteine lysine salt 2.7 g/day | vitamin E 400 mg/day | vitamin A 30000 IU/day + vitamin C 500 mg/day), selective COX-2 inhibitor Celecoxib 200 mg/day. The treatment is administered for 16 weeks. The following parameters are evaluated: 1) clinical (stage and ECOG PS); 2) nutritional (Lean Body Mass-LBM, appetite and resting energy expenditure); 3) laboratory parameters (proinflammatory cytokines, CRP/leptin, reactive oxygen species (ROS) and antioxidant enzymes); 4) quality of life (EORTC QLQ-C30, EQ-5D andEQ-5Dvas).Aphase II non randomized study has been designed to enroll 40 patients with advanced cancer at different sites with symptoms of CACS/OS. To date 19 patients have been enrolled (11 head and neck, 4 breast, 1 ovarian, 1 lung, 1 stomach and 1 pancreatic cancer; all stage IV). 18 patients are currently evaluable. 10 patients were evaluated after 4 months of treatment, 13 after 2 months and 18 after 1 month. As for LBM a mean increase of 1.2 kg (+5.3%) after 1 month (n.s.), 2.3 kg (+10.1%) (p=0.05) after 2months and 3.0 kgs (+14.6%) (p=0.036) after 4months have been registered. As for cytokines: TNF alpha decreased significantly (p<0.05) after 1 month, 2 months and 4 months; IL-6 decreased significantly (p<0.05) after 2 months and 4 months of treatment. ROS significantly decreased (p<0.05) after 2 months and 4 months of treatment. The QL evaluation showed amean percent increase (improved QL) of 28% byEORTC QLQ-C30 and 16.6% by EQ-5Dvas after 1 month of treatment. The study is in progress until completion of accrual.