Abstract #1676: Randomized phase III clinical trial of 5 different arms of treatment for patients with cancer-related anorexia/cachexia syndrome (CACS)
Authors: Giovanni Mantovani, Clelia Madeddu, Roberto Serpe, Filomena Panzone, Giorgia Antoni, Francesca Tanca, Elena Massa, Giorgio Astara, Antonio Maccio
Journal: Cancer Research (2009)

Cancer-related anorexia/cachexia syndrome (CACS) is a multifactorial syndrome exhaustively defined by Evans WJ et al, (Clin Nutr 27:793-799 ,  2008). In April 2005 we started a phase III randomised study to establish the most effective and safest treatment of CACS: primary endpoints were LBM, resting energy expenditure (REE), total daily physical activity, serum levels of IL-6 and TNF-alpha and fatigue. Planned sample size 475 patients. Eligibility criteria: hystologically confirmed tumors of any site; loss of body weight \#8805; 5% in the last 3 months (clinical CACS) and/or high circulating proinflammatory cytokines, ROS and antioxidant enzymes predictive of CACS; life expectancy > 4 months. Patients could be treated with either antineoplastic therapy or supportive care. All patients enrolled received as basic oral treatment: poliphenols + alpha lipoic acid + carbocysteine + Vitamins ACE. Patients were then randomised to one of the following 5 arms: 1) Medroxyprogesterone Acetate (MPA)/ Megestrol Acetate (MA); 2) Pharmaco-nutritional support containing EPA; 3) L-carnitine; 4) Thalidomide; 5) MPA/MA + Pharmaco-nutritional support + L-carnitine + Thalidomide. Treatment duration was 4 months. Interim analyses were planned after every 100 randomized patients. A first interim analysis on 125 patients showed that arm 2 was by far less effective as for LBM, REE and MFSI-SF and therefore was withdrawn from the study. A second interim analysis on 204 patients showed that arm 1 was significantly less effective for primary efficacy endpoints: therefore it was withdrawn from the study. At November 2008, 302 patients were randomized and 283 were evaluable: M/F 167/116, mean age 62.4 years (range 30-84), 120 (42.4%) were elderly (12% were over 75 years). Cancer sites: lung 14.8%, breast 14.1%, colorectal 11.7%, pancreas 8.8%, stomach 6%, head and neck 5.3%, ovary 4.2%; 95.4% patients were stage IV. The Glasgow prognostic score (GPS) distribution was: 0 in 1% of patients, 1 in 23.9%, 2 in 31.3%, 3 in 15.6%, 4 in 28.1% and a rough assessment seems to confirm in our study its correlation with survival. Statistical analysis shows a significant improvement of primary end-points: increase of LBM (assessed by DEXA), decrease of REE, fatigue and IL-6 in arm 5. The ANOVA test shows a trend for arm 5 to be superior to arm 3 as for fatigue and to arm 4 as for REE. No significant difference as for primary outcome variables were observed in comparison to non elderly patients. As for safety, the treatment overall was well tolerated and the patient compliance was good. Two cases of severe toxicities occurred: grade 3 diarrhea in a patient in arm 3 and grade 2 deep vein thrombosis in a patient in arm 1. In conclusion, the interim analyses seem to suggest that the most effective treatment should be the combination regimen. The study is still in progress up to completion of planned accrual of the remaining arms.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1676.