Cancer-related anorexia/cachexia syndrome and oxidative stress: an innovative approach beyond current treatment.
OBJECTIVE
Cancer-related anorexia/cachexia syndrome and oxidative stress play a key role in the progression and outcome of neoplastic disease.


METHODS
On the basis of our previously published studies and clinical experience, we have developed an innovative approach consisting of diet with high polyphenol content (400 mg), p.o. pharmaconutritional support enriched with n - 3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) 2 cans (237 mL each) per day, medroxiprogesterone acetate 500 mg/d, antioxidant treatment with alpha-lipoic acid 300 mg/d plus carbocysteine lysine salt 2.7 g/d plus vitamin E 400 mg/d plus vitamin A 30,000 IU/d plus vitamin C 500 mg/d, and selective cyclooxygenase-2 inhibitor Celecoxib 200 mg/d. The treatment is administered for 16 weeks. The following variables are evaluated: (a) clinical variables (stage and Eastern Cooperative Oncology Group performance status); (b) nutritional variables (lean body mass, appetite, and resting energy expenditure); (c) laboratory variables (serum levels of proinflammatory cytokines, C-reactive protein, and leptin and blood levels of reactive oxygen species and antioxidant enzymes); and (d) quality of life variables (European Organization for Research and Treatment of Cancer QLQ-C30, EQ-5Dindex, and EQ-5DVAS). A phase II nonrandomized study has been designed to enroll 40 patients with advanced cancer at different sites with symptoms of cancer-related anorexia/cachexia syndrome and oxidative stress.


RESULTS
As of January 2004, 28 patients have been enrolled: 25 patients were evaluable and 14 of them have completed the treatment (20 patients have completed 2 months of treatment). As for clinical response, five patients improved, three patients remained unchanged, and six patients worsened. The Eastern Cooperative Oncology Group performance status (grade) 1 remained unchanged. As for nutritional/functional variables, the lean body mass increased significantly at 2 and 4 months. As for laboratory variables, reactive oxygen species decreased significantly and proinflammatory cytokines interleukin-6 and tumor necrosis factor-alpha decreased significantly. As for quality of life, it comprehensively improved after treatment.


CONCLUSIONS
The treatment has been shown to be effective for clinical response, increase of lean body mass, decrease of reactive oxygen species and proinflammatory cytokines, and improvement of quality of life. The treatment has been shown to be safe with good compliance of patients. The study is in progress (14 further patients will be included).
Mantovani
Giovanni
G
Department of Medical Oncology, University of Cagliari, 09042, Italy. mantovan@pacs.unica.it
Madeddu
Clelia
C
Macciò
Antonio
A
Gramignano
Giulia
G
Lusso
Maria Rita
MR
Massa
Elena
E
Astara
Giorgio
G
Serpe
Roberto
R
D000328:Adult; D000368:Aged; D000855:Anorexia / Q000178:diet therapy* / Q000503:physiopathology*; D000975:Antioxidants / Q000627:therapeutic use; D002100:Cachexia / Q000178:diet therapy* / Q000503:physiopathology*; D019587:Dietary Supplements; D005260:Female; D005419:Flavonoids / Q000627:therapeutic use; D006304:Health Status; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications*; D009752:Nutritional Status; D018384:Oxidative Stress; D010636:Phenols / Q000627:therapeutic use; D059808:Polyphenols; D011788:Quality of Life; D017382:Reactive Oxygen Species; D013577:Syndrome; D016896:Treatment Outcome
D000975:Antioxidants; D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D017382:Reactive Oxygen Species