Elsevier

Nutrition

Volume 17, Issue 9, September 2001, Pages 751-755
Nutrition

Pensa meeting
Cancer cachexia and its treatment with fish-oil-enriched nutritional supplementation

https://doi.org/10.1016/S0899-9007(01)00631-1Get rights and content

Abstract

OBJECTIVE: Cachexia is a common condition affecting those with advanced cancer. This review explores mechanisms of cachexia and possible treatments devised with these mechanisms in mind.

METHODS: Selective review of the relevant scientific literature was performed with particular emphasis on studies performed by our group over the past 10 y involving patients with advanced pancreatic cancer.

RESULTS: Cancer cachexia adversely affects patient quality of life and survival. It is characterized by a lack of a normal anabolic response to the provision of apparently adequate nutrition. It appears to result from a persistent response to illness stimulated by the cancer resulting in a proinflammatory cytokine and catabolic hormonal environment. Interventions that ignore this inflammatory milieu have had little success. More promising interventions have a broad antiinflammatory component such as nonsteroidal antiinflammatory drugs or fish oil. Preliminary studies of a combination of fish oil as an antiinflammatory agent with nutritional supplementation show promise in reversing weight loss with apparent gains in lean tissue and performance status in association with normalization of the metabolic environment in patients with advanced pancreatic cancer.

CONCLUSIONS: Cancer cachexia produces a metabolic environment that prevents the appropriate use of supplied nutrition. Antiinflammatory agents such as fish oil in combination with nutritional supplementation may reverse aspects of cachexia.

Introduction

Pancreatic adenocarcinoma is a common condition with a dismal outlook. It is responsible for about 5% of cancer deaths, with a median survival of 4.1 mo.1, 2 More than 80% of cancers are unresectable at diagnosis, and even in those patients suitable for surgical resection the 5-y survival rate is less than 25%.3 The limited effects of chemotherapy and radiotherapy leave little in the way of treatment options for the vast majority of patients with unresectable disease, thus providing a valuable model in which to study the mechanisms and mediators of decline in patients with advanced cancer to maximize supportive treatment with the potential to improve quality and perhaps length of life.

Wigmore et al. reported that 85% of patients with unresectable pancreatic cancer have unintentionally lost weight by the time of diagnosis, with a median weight loss of almost 25% close to the time of death.4 This is a manifestation of the syndrome of cachexia, characterized by anorexia, early satiety, changes in taste perception, weight loss, weakness, anemia, and edema.5 Cachexia is associated with a shorter survival time and reduced quality of life and is the cause of death in perhaps 20% of cancer patients.6, 7, 8, 9, 10 Cachexia is not exclusive to cancer but is also seen in a variety of other inflammatory conditions.

The fundamental difference between the weight loss observed in cachexia and that seen in, e.g., starvation, is the lack of reversibility with feeding.11, 12 This seems to be due to metabolic changes in cachexia similar to those seen after surgery, trauma, or sepsis and driven by similar mediators.

Section snippets

Mechanisms and mediators of cachexia

Most patients with pancreatic cancer likely have inadequate nutrition intake, which contributes substantially to weight loss.13, 14 Patients with cancer cachexia frequently have specific problems that reduce nutrition intake, including physical obstruction of the gastrointestinal tract, nausea, constipation and debility, psychological problems such as depression, and pain and the side effects of treatment with opiates, radiotherapy, and chemotherapy. However, even if these factors are well

Treatment of cancer cachexia

The best way to treat cancer cachexia is to cure the cancer. Unfortunately, this remains a rare achievement. The next obvious option is to increase nutrition intake by enteral or parenteral means.

Two substantial randomized trials have examined the effect of enteral feeding in patients with advanced cancer undergoing chemotherapy.63, 64 Both studies included patients with a variety of cancer types who were randomized to receive or not receive nutrition counseling (to raise their energy and

Fish-oil-based interventions in cancer cachexia

General interest has focused on the properties of ω-3 fatty acids. These are an essential component of the diet and are involved in the synthesis of eicosanoids (prostaglandins, leukotrienes, and thromboxanes) and in membrane, receptor, and enzyme functions. Their usual source in the diet is oily fish. Interest in fish oils, notably eicosapentaenoic acid (EPA), was initially in the cardiovascular field, where their consumption was associated with a reduced tendency to platelet aggregation,

Conclusions

Although progress has been made in understanding the physiologic changes in advanced cancer that give rise to cachexia, it remains a significant cause of morbidity and mortality in malignant disease. The metabolic alterations that occur in these patients might prevent the effective use of additional calories supplied, resulting in ongoing wasting. Broadly speaking, antiinflammatory agents such as fish oil have the potential to normalize these metabolic alterations and may allow the supply of

Acknowledgements

The substantial contribution to work performed in Edinburgh described in this review by Professor Kenneth C. H. Fearon is gratefully acknowledged.

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