Randomized phase III clinical trial of a combined treatment with carnitine + celecoxib ± megestrol acetate for patients with cancer-related anorexia/cachexia syndrome

• Published in: Clinical nutrition (Edinburgh, Scotland) Vol. 31; no. 2; pp. 176 - 182
• Main Authors: Madeddu, Clelia, Dessì, Mariele, Panzone, Filomena, Serpe, Roberto, Antoni, Giorgia, Cau, Maria Chiara, Montaldo, Lorenza, Mela, Quirico, Mura, Marco, Astara, Giorgio, Tanca, Francesca Maria, Macciò, Antonio, Mantovani, Giovanni
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.04.2012; Elsevier
• Subjects: Absorptiometry, Photon; Aged; Aged, 80 and over; Anorexia - complications; Anorexia - drug therapy; Appetite; Biological and medical sciences; Cachexia - complications; Cachexia - drug therapy; Cancer-related anorexia cachexia; Carnitine; Carnitine - therapeutic use; Celecoxib; Combined Modality Therapy; Drug Combinations; Endpoint Determination; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Gastroenterology and Hepatology; Humans; Lean body mass; Male; Megestrol acetate; Megestrol Acetate - therapeutic use; Middle Aged; Neoplasms - complications; Neoplasms - drug therapy; Patient Compliance; Physical activity; Pyrazoles - therapeutic use; Quality of Life; Sulfonamides - therapeutic use; Treatment Outcome; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Lean body mass; Celecoxib; Megestrol acetate; Physical activity; Cancer-related anorexia cachexia; Carnitine; Antineoplastic agent; Phase III trial; Human; Prostaglandin-endoperoxide synthase; Anorexia; Enzyme; Enzyme inhibitor; Metabolic diseases; Cyclooxygenase 2 inhibitor; Cachexia; Megestrol; Acetate; Malignant tumor; Progestagen; Non steroidal antiinflammatory agent; Chemotherapy; Randomization; Treatment; Aminoacid; Combined treatment; Oxidoreductases; Cancer
• ISSN: 0261-5614; 1532-1983
• DOI: 10.1016/j.clnu.2011.10.005

Summary Background & aims A phase III, randomized non-inferiority study was carried out to compare a two-drug combination (including nutraceuticals, i.e. antioxidants) with carnitine + celecoxib ± megestrol acetate for the treatment of cancer-related anorexia/cachexia syndrome (CACS): the primary endpoints were increase of lean body mass (LBM) and improvement of total daily physical activity. Secondary endpoint was: increase of physical performance tested by grip strength and 6-min walk test. Methods Sixty eligible patients were randomly assigned to: arm 1, l -carnitine 4 g/day + Celecoxib 300 mg/day or arm 2, l -carnitine 4 g/day + celecoxib 300 mg/day + megestrol acetate 320 mg/day, all orally. All patients received as basic treatment polyphenols 300 mg/day, lipoic acid 300 mg/day, carbocysteine 2.7 g/day, Vitamin E, A, C. Treatment duration was 4 months. Planned sample size was 60 patients. Results The results did not show a significant difference between treatment arms in both primary and secondary endpoints. Analysis of changes from baseline showed that LBM (by dual-energy X-ray absorptiometry and by L3 computed tomography) increased significantly in both arms as well as physical performance assessed by 6MWT. Toxicity was quite negligible and comparable between arms. Conclusions The results of the present study showed a non-inferiority of arm 1 (two-drug combination) vs arm 2 (two-drug combination + megestrol acetate). Therefore, this simple, feasible, effective, safe, low cost with favorable cost-benefit profile, two-drug approach could be suggested in the clinical practice to implement CACS treatment.