Cancer related anorexia/cachexia and oxidative stress: An innovative approach beyond current treatment
Authors: Giovanni Mantovani, Antonio Macciò, Clelia Madeddu, Giulia Gramignano, Maria R. Lusso, Elena Massa, Giorgio Astara, Roberto Serpe, Miria Mocci, Simona Perboni
Journal: Cancer Research (2004)

1402   Cancer Anorexia/Cachexia Syndrome (CACS) and Oxidative Stress (OS) play a key role in the progression and outcome of cancer. The conventional nutritional approach through enteral/parenteral nutrition has been demonstrated to be ineffective. Synthetic progestagens are to date the only approved drugs, although their use is limited because of significant side effects. An important role may be played by a pharmaco-nutritional support containing EPA, which is able to decrease proinflammatory cytokines and PIF.  Patients and Methods:  Our previously published studies and clinical experience have prompted us to develop 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, medroxyprogesterone acetate 500 mg/day, antioxidant treatment with 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 have been evaluated: 1) clinical (stage and ECOG PS); 2) nutritional (Lean Body Mass, LBM, appetite and resting energy expenditure); 3) laboratory parameters (serum levels of proinflammatory cytokines, CRP and leptin and blood levels of reactive oxygen species (ROS) and antioxidant enzymes); 4) quality of life (EORTC QLQ- C30, EQ-5D and EQ-5D vas). A phase II non randomized study has been designed to enroll 40 patients with advanced cancer at different sites with symptoms of CACS/OS.  Results:  To date 20 patients have been enrolled (12 head and neck, 4 breast, 1 ovarian, 1 lung, 1 stomach and 1 pancreatic cancer; all stage IV). 18 patients are currently evaluable. Ten patients have been evaluated after 4 months of treatment, 13 after 2 months and 18 after 1 month. As for LBM a mean increase of 1.1 kgs (+5.3 %) after 1 month (p=n.s.), 2.3 kgs (+10.1%) (p=0.05) after 2 months and 3.0 kgs (+14.6%) (p=0.036) after 4 months have been recorded. As for proinflammatory cytokines: TNFalpha decreased significantly after 1 month (p=0.015), 2 months (p=0.004) and 4 months (p=0.026) of treatment; IL-6 decreased significantly after 2 months (p=0.001) and 4 months (p=0.006) of treatment. As for ROS, a significant decrease after 2 months (p=0.025) and 4 months (p=0.046) of treatment has been recorded. The evaluation of QL showed a mean percent increase (improved QL) of 28% by EORTC QLQ-C30 and 16.6% by EQ-5Dvas after 1 month of treatment.  Conclusions:  At the interim analysis on the first 20 patients enrolled the treatment appears to be effective for the main parameters studied, safe and to achieve an optimal compliance by patients. The study is in progress until the accrual will be completed. Work supported by Special Program for Experimental Research, Prevention and Medical Education funded by Regione Autonoma Sardegna, Italy, 2002.