Weight Loss In Patients With Pancreatic Cancer - Brief Article

Nutrition Research Newsletter, Nov, 2000

Pancreatic cancer is frequently associated with progressive nutritional decline, with patients losing around 11% of pre-illness stable weight at the time of diagnosis and 25% of pre-illness stable weight near the time of death. It is now widely recognized that proinflammatory cytokines such as tumor necrosis factor (TNF) and interleukin-6 (IL6) can induce a cachectic state when injected into animals. There appears to be a strong link between proinflammatory cytokine activity and the development of cachexia in patients with pancreatic cancer. The n-3 polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been shown to suppress the production of proinflammatory cytokines such as IL-1 and TNF in healthy volunteers. Fish oil is rich in the n-3 fatty acids EPA and DHA. A recent study was designed to test the hypothesis that EPA is one of the biologically active components of fish oil responsible for anticachectic activity.

A total of 26 patients (12 males and 14 females) were recruited to the study: 23 patients had unresectable pancreatic cancer and three patients had unresectable ampullary cancer. At the time of study entry, all patients had lost weight (median weight loss 13% compared with pre-illness stable weight). Weight loss had occurred over a median of four months at a median rate of 2.0 kg/mo. High-purity EPA was provided by Scotia Pharmaceuticals (Carlisle, UK) in the form of gelatin capsules, each containing 500 mg of EPA. The 26 patients recruited received EPA at 1 g/day for the first week, 2 g/day for the second week, 4 g/day for the third week, and 6 g/day thereafter. This dose, requiring patients to take 12 capsules per day, was believed to be the highest that was reasonable to expect this group of patients to tolerate via the oral route.

Patients were reviewed at monthly intervals until death, and all continued to receive high-purity EPA or fish oil until near the time of death. Baseline anthropometry, body composition analysis, and level of the acute-phase protein response (APPR) were assessed in all patients before entry into the study and 4, 8, and 12 weeks thereafter. Over the three-month study period, the principal symptoms possibly associated with administration of the EPA capsules were nausea and steatorrhea. A number of patients found the EPA capsules unpleasant to take because of problems with occasional leakage of the contents, resulting in an unpleasant chemical taste. No patients developed adverse events that fell outside the normal pattern of events for patients with advanced pancreatic cancer.

There was no significant change in median body weight for patients surviving at 4, 8, and 12 weeks after commencement of EPA. Median rate of weight loss decreased significantly after four weeks of EPA compared with pre-study values. This reduction in the rate of weight loss remained significant at 8 and 12 weeks. There was no significant change in mid-arm muscle circumference (MAMC) or triceps skinfold thickness (TSF) in patients after EPA supplementation. Although there was a small increase in energy intake, this difference was not statistically significant.

The data suggest that oral supplementation with high-purity EPA altered the progress of cachexia in this group of patients with advanced pancreatic cancer. Before supplementation, all patients had lost a substantial amount of weight and after supplementation, there was no further significant decline in weight. The rate of weight change was reversed from a median loss of 2 kg/mo before supplementation to a median gain of 0.5 kg/mo after four weeks. After this time, the rate of weight change remained static, suggesting a stabilization of weight. Thus EPA appears to be effective in attenuating cachexia and may be one of the principal components of fish oil responsible for its anticachectic activity.

There was a marked rise in levels of EPA in plasma phospholipids from being undetectable before to representing around 10% of fatty acids after four weeks of EPA supplementation. The percentage of EPA incorporation achieved was roughly twice that seen after supplementation with crude fish oil capsules in pancreatic cancer patients given a final dose equivalent to 2 g of EPA per day after a similar dose-escalation period.

This study shows that EPA would appear to be a safe, effective anticachectic agent. Further study is required to determine whether nutritional supplementation in combination with EPA will result in weight gain rather than weight stability and whether large doses of EPA will have direct antitumor effects in human malignancy.

S. Wingmore, M. Barber, J. Ross, et al., Effect of Oral Eicosapentaenoic Acid on Weight Loss in Patients with Pancreatic Cancer, Nutrition and Cancer 36(2): 177-184 (2000)