Abstract

Abstract Background

Cancer cachexia is a distressing weight loss syndrome commonly seen in advanced cancer patients. It is associated with reduced quality of life and shorter survival time. Eicosapentaenoic acid (EPA) is a long chain polyunsaturated fatty acid found naturally in some fish which has been used to decrease weight loss, promote weight gain and increase survival times in patients affected with cancer cachexia.

To evaluate the effectiveness and safety of EPA in relieving symptoms associated with the cachexia syndrome in patients with advanced cancer.

Studies were sought through an extensive search of a range of electronic databases. Hand searching was conducted on selected journals and reference lists as well as contact made with investigators, manufacturers and experts. The most recent electronic search was conducted in February 2005.

Studies were included in the review if they assessed oral EPA compared with placebo or control in randomised controlled trials of patients with advanced cancer and either a clinical diagnosis of cachexia or self‐reported weight loss of 5% or more.

Both methodological quality evaluation of potential trials and data extraction were conducted by two independent review authors.

Five trials (involving 587 participants) met the inclusion criteria. Three trials compared EPA at different doses with placebo with two outcomes, nutritional status and adverse events comparable across two of the three included trials. In addition, two trials compared different doses of EPA with an active matched control. It was possible to compare the outcomes of weight, quality of life and adverse events across these two trials. There were insufficient data to define the optimal dose of EPA.

There were insufficient data to establish whether oral EPA was better than placebo. Comparisons of EPA combined with a protein energy supplementation versus a protein energy supplementation (without EPA) in the presence of an appetite stimulant (Megestrol Acetate) provided no evidence that EPA improves symptoms associated with the cachexia syndrome often seen in patients with advanced cancer.

Author(s)

Ann Dewey, Chris Baughan, Taraneh P Dean, Bernie Higgins, Ian Johnson

Abstract

Plain language summary

Using an omega‐3 fatty acid made from fish oils to treat cancer related weight loss 

There was insufficient evidence to support the use of oral fish oil (on its own or in the presence of other treatments) for the management of the weight loss syndrome often seen in patients with advanced cancer. Many people with advanced cancer develop a distressing weight loss syndrome. To date, treatment of associated symptoms has proved difficult. More recently, novel approaches have included the use of oral fish oils that can contain the omega‐3 fatty acid eicosapentaenoic acid (or EPA) to stabilise weight loss and promote weight gain. This review of trials found that in weight losing persons with advanced pancreatic cancer, an EPA nutritional supplement was no better than a non EPA nutritional supplement. However, there was insufficient evidence to draw conclusions about its use in patients who have cancer of other tumour types.

Author(s)

Ann Dewey, Chris Baughan, Taraneh P Dean, Bernie Higgins, Ian Johnson

Reviewer's Conclusions

Authors' conclusions

Implications for practice

The conduct of this systematic review did not enable us to confirm or refute previous literature on the use of EPA and it was not possible to recommend its use in clinical practice. Whilst the results from this systematic review suggests that there is little evidence of harm from using EPA it may not be reasonable to suggest its use in people who are very ill or if palatability is low and problems of compliance occur. There appears to be no significant improvement in management of symptoms by the addition of EPA to that gained from patients taking a high calorie, high protein nutritional supplement with or without the addition of the appetite stimulant, Megestrol Acetate (MA). Indeed it may be that combining EPA with MA may have a slight inhibitory action on MA.

Implications for research

The conduct of this systematic review has revealed a paucity of well‐conducted randomised controlled trials to adequately answer the review questions posed. Furthermore many of the trials were poorly reported which made it difficult and time‐consuming to assess their suitability. However, we found improved reporting in those trials which appear to have been designed and reported in accordance with the Consolidated Standards of Reporting Trials statement (CONSORT Statement) which includes a 22‐item checklist and a flow diagram and its use should be encouraged (Altman 2001). There is a need to conduct good quality large scale randomised controlled trials using EPA compared to placebo with different cancer types. In particular, the potential survival advantage of the addition of EPA needs to be explored. We also found that many of the included trials permitted concurrent use of other supportive therapies such as corticosteroids (four of the five trials) palliative chemotherapy (one trial) and radiotherapy (two trials) which may have masked the true benefit of the addition of EPA alone. Future trials could exclude other supportive therapies or incorporate appropriate stratification. In addition, it may be necessary for future studies to consider using a more palatable formulation of EPA. Finally, we found a paucity of studies that recruit patients at an early stage in their disease progression. Recruiting patients in to the study with minimal weight loss and at an earlier stage may provide a better opportunity to encourage compliance and provide enough time to assess meaningful improvements. The challenges will be identifying and recruiting suitable cancer patients into such a study.