Randomised phase III clinical trial of 5 different arms of treatment on 332 patients with cancer cachexia

Abstract

Background and Objective: A phase III randomised study was carried out to establish the most effective and safest treatment to improve the primary endpoints of cancer cachexia: lean body mass (LBM), resting energy expenditure (REE), fatigue; and relevant secondary endpoints: appetite, quality of life, grip strength, Glasgow Prognostic Score (GPS) and proinflammatory cytokines. Patients: Three hundred and thirty-two assessable patients with cancer-related anorexia/cachexia syndrome (CACS) were randomly assigned to one of five arms of treatment: 1 - medroxyprogesterone 500 mg/d or megestrol acetate 320 mg/d; 2 - oral supplementation with eicosapentaenoic acid (EPA); 3 - L-carnitine 4 g/d; 4 - thalidomide 200 mg/d; 5 - a combination of the above. Treatment duration: 4 months. Results: Analysis of variance showed a significant difference between the treatment arms. A post hoc analysis showed the superiority of arm 5 over the others for all primary endpoints. An analysis of changes from baseline showed that LBM (by dual-energy X-ray absorptiometry and by L3 computed tomography) significantly increased in arm 5. REE decreased significantly and fatigue improved significantly in arm 5. Appetite increased significantly in arm 5. IL-6 decreased significantly in arm 5 and 4. GPS significantly decreased in arms 5, 4 and 3. Total daily physical activity showed that total energy and active energy expenditure increased significantly in arm 5. Eastern Cooperative Oncology group-Performance Status (ECOG-PS) significantly decreased in arms 5, 4 and 3. Toxicity was substantially negligible, comparable between treatment arms. Conclusions: The most effective treatment for all three primary efficacy endpoints as well as secondary endpoints appetite, IL-6, GPS and ECOG PS was the combination regimen that included all selected agents.