Effects of eicosapentaenoic and docosahexaenoic n-3 fatty acids from fish oil and preferential Cox-2 inhibition on systemic syndromes in patients with advanced lung cancer

• Published in: Nutrition and cancer 2007-01, Vol.59 (1), p.14-20
• Main Authors: Cerchietti, L.C.A, Navigante, A.H, Castro, M.A
• Format: Article
• Language: English
• Subjects: acute phase proteins; Adult; Aged; Aged, 80 and over; appetite; Appetite - drug effects; Biological and medical sciences; body weight; C-reactive protein; C-Reactive Protein - analysis; Cachexia - drug therapy; Celecoxib; clinical trials; Cohort Studies; Cyclooxygenase 2 Inhibitors - therapeutic use; cytokines; Dietary Supplements; docosahexaenoic acid; Docosahexaenoic Acids - therapeutic use; dosage; Dose-Response Relationship, Drug; Drug Therapy, Combination; eicosapentaenoic acid; Eicosapentaenoic Acid - therapeutic use; enzyme inhibitors; Epidemiology; Fatigue - drug therapy; Fatty Acids, Omega-3 - therapeutic use; Female; fish oils; Fish Oils - chemistry; health status; Humans; inflammation; lung neoplasms; Lung Neoplasms - complications; Male; Maximum Tolerated Dose; Medical sciences; Middle Aged; Muscle Strength - drug effects; muscle tissues; nutritional support; oral administration; Other treatments; pathophysiology; Patient Compliance; patients; Pneumology; prostaglandin synthase; Pyrazoles - therapeutic use; signs and symptoms (animals and humans); Sulfonamides - therapeutic use; Syndrome; Systemic Immune-Metabolic Syndrome; Treatment. General aspects; Tumors; Tumors of the respiratory system and mediastinum; Weight Gain - drug effects
• ISSN: 0163-5581; 1532-7914
• DOI: 10.1080/01635580701365068

Under the common denomination of Systemic Immune-Metabolic Syndrome (SIMS), we grouped many symptoms that share a similar pathophysiologic background. SIMS is the result of the dysfunctional interaction of tumor cells, stroma cells, and the immune system, leading to the release of cytokines and other systemic mediators such as eicosanoids. SIMS includes systemic syndromes such as paraneoplastic hemopathies, hypercalcemia, coagulopathies, fatigue, weakness, cachexia, chronic nausea, anorexia, and early satiety among others. Eicosapentaenoic and docosahexaenoic n-3 fatty acids from fish oil can help in the management of persistent chronic inflammatory states, but treatment's compliance is generally poor. Preferentially, Cox-2 inhibition can create a favorable pattern of cytokines by decreasing the production of certain eicosanoids, although their role in SIMS is unknown. The aim of this study was to test the hypothesis that by modulating systemic inflammation through an eicosanoid-targeted approach, some of the symptoms of the SIMS could be controlled. We exclusively evaluated 12 patients for compliance. Patients were assigned 1 of the 4 treatment groups (15-, 12-, 9-, or 6-g dose, fractionated every 8 h). For patients assigned to 15 and 12 doses, the overall compliance was very poor and unsatisfactory for patients receiving the 9-g dose. The maximum tolerable dose was calculated to be around 2 capsules tid (6 g of fish oil per day). A second cohort of 22 patients with advanced lung cancer and SIMS were randomly assigned to receive either fish oil, 2 g tid, plus placebo capsules bid (n = 12) or fish oil, 2 g tid, plus celecoxib 200 mg bid (n = 10). All patients in both groups received oral food supplementation. After 6 wk of treatment, patients receiving fish oil + placebo or fish oil + celecoxib showed significantly more appetite, less fatigue, and lower C-reactive protein (C-RP) values than their respective baselines values (P < 0.02 for all the comparisons). Additionally, patients in the fish oil + celecoxib group also improved their body weight and muscle strength compared to baseline values (P < 0.02 for all the comparisons). Comparing both groups, patients receiving fish oil + celecoxib showed significantly lower C-RP levels (P = 0.005, t-test), higher muscle strength (P = 0.002, t-test) and body weight (P = 0.05, t-test) than patients receiving fish oil + placebo. The addition of celecoxib improved the control of the acute phase protein response, tota