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

Abstract

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, total body weight, and muscle strength. Additionally, the consistent nutritional support used in our patients could have helped to maximize the pharmacological effects of fish oil and/or celecoxib. This study shows that by modulating the eicosanoid metabolism using a combination of n-3 fatty acids and cyclooxygenase-2 inhibitor, some of the signs and symptoms associated with a SIMS could be ameliorated.

Emerging Prognostic Biomarkers in Non Small Cell Lung Cancer Patients:Impact of Treatment with Nimesulide (COX-2 Inhibitor) Combined with Chemotherapy

“…Similar to the present study, Cerchietti et al [28] studied the effect of COX -2 inhibitors as anti-cancer agents and as adjuvant therapy and found that they are more potent than chemotherapy alone in inducing apoptosis of NSCLC cells and improving patients survival. In addition, Gadgeel et al [29] demonstrated the effectiveness of the dual blockade of epidermal growth factor receptor (EGFR) and COX-2 in addition to conventional chemotherapy in NSCLC.…”

Exercise and Nutrition Interventions in Advanced Lung Cancer: A Systematic Review

“…• Not limited to advanced NSCLC (n=11) [21][22][23][24][25][26][27][28][29][30][31] • Drug trial (n=1) 32 • Laboratory study (n=1) 33 • Pending publication (n=1) 38 found no significant differences in body weight change between groups receiving an active epa-containing intervention and a control supplement. Fat-free mass as determined by bioelectrical impedance declined in both groups, but a statistically larger loss of muscle was observed at 5 weeks in the control group ( p < 0.05).…”

“…The electronic database searches identified nine abstracts of interest, and a further twelve were identified by the hand searches or by contacting investigators in the field. After retrieval of twenty-one full-text articles, fifteen studies were excluded [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] as detailed in Figure 1. The present systematic review includes six papers detailing five studies with a total of 203 participants.…”

Dietary Supplement Use in Cancer Care: Help or Harm

“…Doses were limited by gastrointestinal toxicity, mainly diarrhea, without any reports of serious adverse effect on coagulation or tumor response. However, for acceptable compliance over time, a much lower dose of fish oil, approximately 6 g per day, was found to be the maximum tolerated in a trial of subjects with advanced lung cancer [167].…”

“…When combined with megase, the conventional treatment for cancerrelated anorexia, no additional benefit was seen by adding 2.18 g of EPA per day [169]. However, combining fish oil (2 g three times a day) with celecoxib (200 mg twice a day) showed significantly greater improvements in appetite, fatigue, body weight, and muscle strength than with fish oil alone in a small group of subjects with advanced lung cancer [167]. C-reactive protein levels were also significantly lower in the combination group, suggesting that fish oil, as well as celecoxib, may have their benefit through interference with inflammation.…”