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Weight loss in advanced cancer patients is refractory to conventional nutritional support. This may be due to metabolic changes mediated by proinflammatory cytokines, hormones, and tumor-derived products. We previously showed that a nutritional supplement enriched with fish oil will reverse weight loss in patients with pancreatic cancer cachexia. The present study examines the effect of this supplement on a number of mediators thought to play a role in cancer cachexia. Twenty weight-losing patients with pancreatic cancer were asked to consume a nutritional supplement providing 600 kcal and 2 g of eicosapentaenoic acid per day. At baseline and after 3 wk, patients were weighed and samples were collected to measure serum concentrations of interleukin (IL)-6 and its soluble receptor tumor necrosis factor receptors I and II, cortisol, insulin, and leptin, peripheral blood mononuclear cell production of IL-1 beta, IL-6, and tumor necrosis factor, and urinary excretion of proteolysis inducing factor. After 3 wk of consumption of the fish oil-enriched nutritional supplement, there was a significant fall in production of IL-6 (from median 16.5 to 13.7 ng/ml, P = 0.015), a rise in serum insulin concentration (from 3.3 to 5.0 mU/l, P = 0.0064), a fall in the cortisol-to-insulin ratio (P = 0.0084), and a fall in the proportion of patients excreting proteolysis inducing factor (from 88% to 40%, P = 0.008). These changes occurred in association with weight gain (median 1 kg, P = 0.024). Various mediators of catabolism in cachexia are modulated by administration of a fish oil-enriched nutritional supplement in pancreatic cancer patients. This may account for the reversal of weight loss in patients consuming this supplement. [ABSTRACT FROM AUTHOR]

Eicosapentaenoic acid (EPA) has been shown to modulate aspects of the inflammatory response that may contribute to weight loss in cancer. This study aimed to evaluate the acceptability and effects of oral supplementation with high purity EPA in weight-losing patients with advanced pancreatic cancer. Twenty-six patients were entered into the study. EPA (95% pure) was administered as free acid starting at 1 g/day; the dose was increased to 6 g/day over four weeks, and then a maintenance dose of 6 g/day was administered. Patients were assessed before EPA and at 4, 8, and 12 weeks while receiving EPA, for weight, body composition, hematologic and clinical chemistry variables, acute-phase protein response, and performance status. Overall survival was noted. Supplementation was well tolerated, with only five patients experiencing side effects possibly attributable to the EPA. Before starting EPA, all patients had been losing weight at a median rate of 2 kg/mo. In general, after EPA supplementation, weight was stable. After four weeks of EPA supplementation, patients had a median weight gain of 0.5 kg (p = 0.0009 vs. rate of weight loss at baseline), and this stabilization of weight persisted over the 12-week study period. Total body water as a percentage of body weight remained stable, as did the proportion of patients with an acute phase protein response, patients' nutritional intake, and performance status. Overall median survival from diagnosis in this study was 203 days. This study suggests that EPA is well tolerated, may stabilize weight in cachectic pancreatic cancer patients, and should be tested as an anticachectic agent in controlled trials. [ABSTRACT FROM AUTHOR]

Abstract: Weight loss and the acute-phase response have been associated with poor quality of life and survival in advanced pancreatic cancer; however, little information is available on changes in these factors over time and their interrelationships. This study examined changes in weight, Karnofsky performance status, C-reactive protein (CRP), and serum albumin in 25 patients with advanced pancreatic cancer given supportive symptomatic treatment only. Patients were assessed at approximately monthly intervals on a total of 70 occasions, allowing assessment of changes over 37 intervals. Overall, patients had a median weight loss of 2.3 kg/28 days. Median CRP levels rose by 15 mg/l, and serum albumin fell by 1 g/l on average over 28 days. Karnofsky performance status fell by 4 points every 28 days. The nine patients assessed close to death were compared with the 13 assessed close to diagnosis. The increase in CRP level and fall in weight and performance status were significantly greater within eight weeks of death than within eight weeks of diagnosis. Among patients close to diagnosis, 13% had an elevated CRP compared with 100% of those close to death. In multivariate analysis, Karnofsky performance status was significantly associated with percent weight loss and CRP levels. These data further implicate the acute-phase protein response as being associated with the progressive weight loss seen in patients with advanced pancreatic cancer. Changes appear to accelerate close to death. Moreover, the development of cachexia is associated with a reduction in patients 'functional capacity. [ABSTRACT FROM AUTHOR]