title: A phase II study with antioxidants, both in the diet and supplemented, pharmaconutritional support, progestagen, and anti-cyclooxygenase-2 showing efficacy and safety in patients with cancer-related anorexia/cachexia and oxidative stress.
abstract: OBJECTIVE
  To test the efficacy and safety of an integrated treatment based on a pharmaconutritional support, antioxidants, and drugs, all given orally, in a population of advanced cancer patients with cancer-related anorexia/cachexia and oxidative stress.
  
  
  METHODS
  An open early-phase II study was designed according to the Simon two-stage design. The integrated treatment consisted of diet with high polyphenols content (400 mg), antioxidant treatment (300 mg/d alpha-lipoic acid + 2.7 g/d carbocysteine lysine salt + 400 mg/d vitamin E + 30,000 IU/d vitamin A + 500 mg/d vitamin C), and pharmaconutritional support enriched with 2 cans per day (n-3)-PUFA (eicosapentaenoic acid and docosahexaenoic acid), 500 mg/d medroxyprogesterone acetate, and 200 mg/d selective cyclooxygenase-2 inhibitor celecoxib. The treatment duration was 4 months. The following variables were evaluated: (a) clinical (Eastern Cooperative Oncology Group performance status); (b) nutritional [lean body mass (LBM), appetite, and resting energy expenditure]; (c) laboratory [proinflammatory cytokines and leptin, reactive oxygen species (ROS) and antioxidant enzymes]; (d) quality of life (European Organization for Research and Treatment of Cancer QLQ-C30, Euro QL-5D, and MFSI-SF).
  
  
  RESULTS
  From July 2002 to January 2005, 44 patients were enrolled. Of these, 39 completed the treatment and were assessable. Body weight increased significantly from baseline as did LBM and appetite. There was an important decrease of proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha, and a negative relationship worthy of note was only found between LBM and IL-6 changes. As for quality of life evaluation, there was a marked improvement in the European Organization for Research and Treatment of Cancer QLQ-C30, Euro QL-5D(VAS), and multidimensional fatigue symptom inventory-short form scores. At the end of the study, 22 of the 39 patients were "responders" or "high responders." The minimum required was 21; therefore, the treatment was effective and more importantly was shown to be safe.
  
  
  CONCLUSIONS
  The efficacy and safety of the treatment have been shown by the study; therefore, a randomized phase III study is warranted.
authors.affiliation: Cattedra e Divisione di Oncologia Medica, Università di Cagliari, Policlinico Universitario, Presidio di Monserrato, SS 554, KM 4.500, 09042 Monserrato, Cagliari, Italy. mantovan@pacs.unica.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Mantovani
authors.forename: Antonio
authors.initials: A
authors.lastname: Macciò
authors.forename: Clelia
authors.initials: C
authors.lastname: Madeddu
authors.forename: Giulia
authors.initials: G
authors.lastname: Gramignano
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Lusso
authors.forename: Roberto
authors.initials: R
authors.lastname: Serpe
authors.forename: Elena
authors.initials: E
authors.lastname: Massa
authors.forename: Giorgio
authors.initials: G
authors.lastname: Astara
authors.forename: Laura
authors.initials: L
authors.lastname: Deiana
mesh_terms: D000328:Adult; D000368:Aged; D000855:Anorexia / Q000178:diet therapy* / Q000209:etiology; D001205:Ascorbic Acid / Q000008:administration & dosage; D002100:Cachexia / Q000178:diet therapy* / Q000209:etiology; D002233:Carbocysteine / Q000008:administration & dosage; D000068579:Celecoxib; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000008:administration & dosage; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008525:Medroxyprogesterone / Q000008:administration & dosage; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications*; D018529:Nutritional Support / Q000379:methods*; D018384:Oxidative Stress; D011720:Pyrazoles / Q000008:administration & dosage; D018709:Statistics, Nonparametric; D013449:Sulfonamides / Q000008:administration & dosage; D008063:Thioctic Acid / Q000008:administration & dosage; D016896:Treatment Outcome; D014801:Vitamin A / Q000008:administration & dosage; D014810:Vitamin E / Q000008:administration & dosage
chemical_list: D011720:Pyrazoles; D013449:Sulfonamides; D014801:Vitamin A; D014810:Vitamin E; D004281:Docosahexaenoic Acids; D008063:Thioctic Acid; D002233:Carbocysteine; D008525:Medroxyprogesterone; D000068579:Celecoxib; D001205:Ascorbic Acid