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The debate regarding the use of EPA-enriched oral nutritional supplements (ONS) versus standard oral nutritional supplements with cancer patients has been ongoing for several years and it continues to be a hot topic in the area of cancer cachexia.
This article aims to summarise recent research and guidelines, and to suggest a step-by-step approach to choosing ONS in this patient group.
Cancer cachexia is a multifactorial syndrome defined by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment. It is characterised by progressive wasting of tissues, severe weight loss, anorexia, early satiety, weakness, metabolic alterations and inflammation.
Over the last ten years research has focused on the effect of Eicosapentaenoic Acid (EPA) in down regulating the inflammatory process, reducing muscle breakdown and attenuating the acute phase response within the cachectic patient. Early studies into supplementation with EPA in weight-losing cancer patients yielded promising results, including preservation of lean body mass (LBM), increased physical activity, improved appetite and weight gain.
However, these studies were generally small, non-randomised or uncontrolled. Subsequent large randomised clinical trials failed to show the same benefit on lean body mass and a systematic Cochrane review in 2007 concluded that there was insufficient evidence that EPA provides a benefit over placebo on cancer cachexia and related symptoms.
However in the last three years, several studies have again raised the potential benefits of EPA in preventing loss of LBM and maintaining or gaining LBM in cancer patients.
Three of these key studies are summarised in Table 1.
In 2011 an international panel of experts developed a consensus statement on the definition and classification of cancer cachexia. It was agreed that cachexia syndrome can develop progressively through various stages – precachexia to cachexia to refractory cachexia. The stages are outlined in Table 2.
It has been noted that a particular weakness of many cachexia intervention trials was to include patients in the terminal stage alongside earlier stage individuals, grouping together patients with extremely wide ranges of weight loss. Patients with refractory cachexia are unlikely to benefit from interventions aimed at reversing muscle and weight loss. The Cochrane review in 2007 included trials of patients with a confirmed diagnosis of incurable or advanced cancer, and either a reported weight loss of ≥ 5% or clinical diagnosis of cachexia. Therefore, refractory cachexia may have been present in the patient populations of these trials.
The patients included in the trials in Table 1 had generally mild or insignificant weight loss, and may have been in the pre-cachexia stage. Therefore, EPA supplementation may be expected to be more effective when implemented early within the stages of cachexia, with the aim of preventing losses and maintaining muscle mass. This suggests that stage of cachexia should therefore be included as part of a nutritional assessment and considered when choosing ONS for cancer patients.
The following steps may be useful to guide when, if and how to use ONS with cancer patients, based on the current available evidence.
Step 1 – Assessment of the patient
To determine stage of cancer cachexia, a dietetic assessment should include percentage weight loss, BMI, anthropometric measurements, inflammatory markers such as CRP and blood glucose, as well as appetite, dietary intake, GI symptoms and treatment side effects. Information should be gathered on performance status and prognosis. These should be assessed ideally within 4 weeks of cancer diagnosis.
Once stage of cachexia has been determined, nutritional goals of care can be set and a treatment plan initiated.
Step 2 – Nutritional Management
Before ONS are recommended, it is vital to consider other causes of unintentional weight loss and anorexia such as mechanical problems and treatment side effects and treat these accordingly with individualised dietary advice. Exercise prescription including resistance training is crucial to increase muscle mass and prevent deterioration in all patients with cancer, especially those with cachexia. This will depend on individual patient needs and guidance should be sought from qualified physiotherapists.
For patients with refractory cachexia the focus of dietetic care should be on maintaining or improving quality of life and comfort, increasing enjoyment of food and providing reassurance and support to both patients and carers.
Step 3 – Choice of Oral Nutritional Supplements
Following nutritional assessment, the decision when choosing between EPA-enriched ONS and standard ONS for each individual patient will depend on the stage of cachexia, the severity of cachexia and the overall goals of care. As the goal of care in precachexia is preventive intervention i.e. to prevent the progression into cachexia, EPA-enriched ONS should be first choice with these patients.
In the cachexia stage the goal of care is to maintain body weight and muscle mass and where feasible reverse losses. The treatment approach should be multimodal and similar to pre-cachexia.
However, if a patient has a severe degree of cachexia, treatment with EPA supplementation is likely to yield minimal to no clinical effects. Therefore the decision on EPA-enriched ONS should be based on the severity of the cachexia and the patient’s tolerance of ONS. EPA-enriched ONS may not be first choice with these patients but should still be considered. In refractory cachexia, EPA supplementation is unlikely to have any benefit. ONS should only be recommended at this stage when appropriate and well tolerated.
Step 4 – Advice on EPA-enriched ONS
When patients are commencing EPA-enriched ONS, they must be given tailored specific advice to ensure they receive the optimum benefit. The recommended dose of EPA is 2g per day. Recipe ideas may help to improve compliance and reduce taste fatigue. If EPA-enriched ONS are not tolerated by the patient, the option of standard ONS plus EPA capsules or liquid should be considered as an alternative.
To maximise phospholipid EPA concentration it is important to consider baseline dietary intake of EPA and encourage intake of dietary sources such as oily fish as tolerated. Cautions for the use of EPA supplementation include fish allergy and anticoagulation therapy. It is therefore recommended to consult with a medical practitioner before recommending EPA supplements in these patient groups.
Step 5 – Review
Patients prescribed EPA enriched ONS should be reviewed every 4 to 8 weeks to assess anthropometry, compliance and tolerance, and to reassess stage of cachexia. If positive outcomes such as maintenance or gain of weight and/or muscle strength and good compliance are evident, the supplements should be continued and reviewed at regular intervals. If outcomes are negative, EPA enriched ONS should be discontinued and alternatives considered.
In conclusion, nutrition support, exercise and anti-inflammatory agents such as EPA are all part of a multimodal approach to managing cancer cachexia. EPA supplementation appears to be more effective if commenced earlier rather than later in the cachexia spectrum. Early identification of at risk patients is essential in order to achieve maximum benefit. The dietitian has a vital role in guiding the appropriate use of EPA enriched ONS with cancer patients.
References available on request.