Cancer-related fatigue

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Abstract

Fatigue is a common symptom in patients with cancer and in disease-free survivors. It has a significant impact on the quality of life. Although subjective fatigue is often related to objective changes in physical functioning or impaired performance status, the two phenomena are not synonymous and need to be distinguished. A number of robust and reliable assessment instruments to measure fatigue severity are now available and criteria for cancer-related fatigue syndrome have been proposed. The underlying mechanisms and pathophysiology of cancer-related fatigue are unclear. Management strategies include the use of psycho-educational interventions, exercise programmes and pharmacological treatments. The best evidence for the effectiveness of drug treatments is for the haematopoietic agents in anaemic patients undergoing chemotherapy and for methylphenidate in an on-treatment population.

Introduction

Cancer-related fatigue (CRF) is a subjective sensation that is disproportional to the widely recognised feeling of being tired. There is no consensus as to what CRF is and its use in a clinical setting is often colloquial rather than specific.1 However, it is accepted as a separate entity from the tiredness experienced by the general population. It is characterised by being pervasive and not relieved by rest.2 CRF can occur at the time of diagnosis and becomes increasingly prevalent with advancing disease.3, 4 It is a side-effect of surgery, chemotherapy and radiotherapy.5, 6, 7 CRF can also affect disease-free survivors.8

Section snippets

What is cancer-related fatigue?

There is some confusion in the literature regarding the terminology of fatigue. Unfortunately, the same term can be used to describe both an objective physical or mental decrement in performance and a subjective mental state. Both types of fatigue are usually found to a greater or lesser extent in the same individual. However, there is no direct correspondence between the two phenomena. It is quite possible to feel extremely subjectively fatigued but to perform relatively normally on objective

How can cancer-related fatigue be measured?

As a subjective state the most appropriate way to measure fatigue is to use self-report measures. At the simplest level fatigue can be measured by using a single item or a single visual analogue scale, either alone or as part of a broader quality of life assessment tool.11, 12, 13 A single-item, 11-point, numerical rating scale has been advocated as a screening tool for CRF by the National Comprehensive Cancer Network (NCCN).14 The NCCN guidelines recommend that patients with a score of 0–3

How common is cancer-related fatigue?

As the previous discussion has suggested, the prevalence of fatigue is likely to vary depending upon the assessment instrument used and the ‘threshold’ above which patients are considered to have ‘significant’ fatigue. At the most basic level, prevalence can be gauged by asking patients how fatigued they have felt in the previous month. In a multi-centre survey of heterogenous cancer patients, 58% reported that fatigue had affected them ‘somewhat’, ‘quite a bit’ or ‘very much’ in the past month.

What are the causes of cancer-related fatigue?

The underlying mechanism or ‘final common pathway’ of cancer-related fatigue remains unclear. Indeed it is unlikely that any single mechanism will ever be identified, as the symptom is almost certainly multi-factorial in origin. Although many studies have reported on the correlates of fatigue and have speculated on the cause of this symptom, there have been very few studies that have tested specific hypotheses about the underlying mechanism.

Prue and colleagues reported that most studies of CRF

How can cancer-related fatigue be treated?

Three broad approaches to tackling CRF have been investigated and these form the basis for most fatigue management programmes.

Professional guidelines

The NCCN first published evidence-based guidelines on the management of CRF in 2000. The guidelines are freely available online and are updated annually.14 The guidelines provide advice on the management of fatigue in patients on treatment, off treatment and in advanced disease. Most of the recommendations in the guidelines are graded at level 2A (uniform NCCN consensus but lower level of evidence, including clinical experience). It is recommended that patients with moderate to severe fatigue

Conclusions

Fatigue is a common and distressing symptom affecting patients with cancer from the time of diagnosis, throughout treatment and into advanced disease. It can also affect disease-free survivors sometimes for years after treatment has finished. Further work is required to understand the pathophysiology of CRF and to develop new treatment approaches. Existing management strategies require further evaluation, ideally using large scale, multi-centre RCTs.

Conflict of interest statement

Dr. Stone received a £15k educational grant from Ortho-biotech (UK) in 2001 to undertake a study of red-cell functioning in patients with cancer.

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