A phase II study with antioxidants, pharmaco-nutritional support, progestagen and anti-COX-2 showing efficacy and safety in patients with cancer-related anorexia/cachexia (CACS) and oxidative stress (OS)

Abstract

8195 Background: A phase II non randomized study has been designed to enroll 39 advanced cancer patients with symptoms of CACS/OS to evaluate the efficacy and tolerability of 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/day, medroxyprogesterone acetate 500 mg/day, antioxidant treatment (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. Patients and Methods: 34 patients with advanced tumors at different sites (mainly head and neck and lung)have been enrolled. The treatment duration was 16 weeks. The following parameters have been evaluated: 1) clinical (objective clinical response and ECOG PS); 2) nutritional (Lean Body Mass, LBM, appetite and resting energy expenditure, REE); 3) laboratory (proinflammatory cytokines and leptin, reactive oxygen species (ROS) and antioxidant enzymes); 4) quality of life (EORTC QLQ- C30, EQ-5D and MFSI-SF). Results: At November 2004 29 patients are evaluable. LBM increased 1.1 kgs (+3.7%, N.S.) after 1 month, 1.6 kgs (+7.0%, p=0.035) after 2 months and 1.9 kgs (+8.7%, p=0.049) after 4 months. Appetite increased significantly after 1, 2 and 4 months of treatment. The REE studied in 3 patients decreased after 4 months of treatment. The serum levels of proinflammatory cytokines IL-6 and TNFalpha significantly decreased during treatment. As for QL evaluation, the EORTC QLQ-C30, EQ-5D and MSFI-SF scores significantly improved after 1, 2 and 4 months of treatment. The interim analysis on 29 patients currently evaluable shows 16 responses (12 “responders” and 4 “high responders”). Conclusion: According to the 2 stage Simon’s design criteria for Phase II studies the treatment is to be considered effective. Moreover, the treatment has demonstrated to be safe. The study is in progress to complete the accrual. Work Supported by: Italian Ministry of University and Scientific Research, Rome, Italy: National Research Project No. 2004067078. No significant financial relationships to disclose.