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Management of fatigue in patients with cancer – A practical overview

Cancer Treatment Reviews, 6, 40, pages 791 - 799


Cancer-related fatigue (CRF) is a serious clinical problem and is one of the most common symptoms experienced by cancer patients. CRF has deleterious effects on many aspects of patient quality of life including their physical, psychological and social well-being. It can also limit their ability to function, socialise and participate in previously enjoyable activities. The aetiology of CRF is complex and multidimensional, involving many potentially contributing elements. These include tumour-related factors and comorbid medical/psychological conditions and also side effects associated with anti-cancer therapies or other medications. Barriers to the effective management of CRF exist both on the side of physicians and patients, and as a result CRF often remains unrecognised and undiscussed in clinical practice. A change of approach is required, where fatigue is treated as central to patient management during and after systemic anti-cancer treatment. In this review we summarise factors involved in the aetiology of CRF and the barriers to its effective management, as well as factors involved in the screening, diagnosis and treatment of cancer patients experiencing fatigue. Pharmacological and non-pharmacological approaches to its management are also reviewed. We suggest an algorithm for the process of managing CRF, guided by our experiences in The Netherlands, which we hope may provide a useful tool to healthcare professionals dealing with cancer patients in their daily practice. Although CRF is a serious and complex clinical problem, if it is worked through in a structured and comprehensive way, effective management has the potential to much improve patient quality of life.

Keywords: Anaemia, Cancer-related fatigue, Diagnosis, Multidisciplinary management, Screening.


Cancer-related fatigue (CRF) is a serious and complex clinical problem [1] and is one of the most common symptoms experienced by oncology patients [2], [3], and [4]. The proportion of patients experiencing CRF varies widely in the literature, but has generally been reported as affecting between ∼40–100% of those with cancer overall [4], [5], [6], [7], [8], and [9]. The variation in rates is likely due to the fact that fatigue is impacted not only by disease stage and status, but also because there is a lack of commonly accepted diagnostic criteria and assessment tools. However, rates can still vary between studies when the same diagnostic criteria are used, reflecting a lack of consistency in how these criteria are applied [10] . CRF can occur before, during and even long after anti-cancer treatment has been completed [4] . Up to 40% of patients report fatigue at diagnosis and virtually all patients experience fatigue at some point during cancer therapy [4] ; reported rates are 80% and 90% for patients being treated with chemotherapy or radiotherapy, respectively [4] . In the post-treatment population, reported CRF rates range from 17% to 21% when strict ICD-10 criteria are applied [11] and from 33% to 53% when other criteria are used [12] . A further study found that 22% of cancer survivors had persistent, severe fatigue in the year following anticancer therapy [13] . Although there is no universally accepted definition of CRF, the National Comprehensive Cancer Network® (NCCN®) defines it as ‘a distressing, persistent, subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment, that is not proportional to recent activity and interferes with usual functioning’ [9] .

Impact of CRF on patients

In comparison to the fatigue experienced by healthy individuals, CRF is differentiated by its severity and the fact that it is often not alleviated by rest or sleep [14] . CRF has deleterious effects on many aspects of patient quality of life [4], [5], [15], and [16]. Specifically, it can significantly impact on a patient’s physical, psychological, social and spiritual well-being, as well as limiting their ability to function, socialise and participate in previously enjoyable activities [16] . It is not only a cause of stress and anxiety for patients but can also have an impact on their family members/caregivers [17] .

The aetiology of CRF

The aetiology of CRF is complex and multidimensional and involves a vast array of potentially contributing factors ( Fig. 1 ) [14] . Anaemia has been linked with poor prognosis and fatigue [18] and is a condition commonly encountered in cancer patients. Fatigue and anaemia are sometimes used interchangeably in the literature but anaemia is actually only one of many possible causes of CRF [14] . Other potentially contributing tumour-related factors include electrolyte abnormalities, dehydration, cachexia, thrombosis/pulmonary embolism, renal failure, liver failure, hypoxia, adrenal insufficiency, neurological deficit, etc. Physical symptoms caused by the underlying tumour or its treatment can also have an impact; the symptoms most strongly correlated with fatigue are pain and dyspnoea. Loss of appetite commonly occurs in cancer patients and can lead to malnutrition and fatigue. This can be exacerbated in patients with more advanced disease who may also experience difficulty with swallowing. The possible impact of any comorbid medical (e.g., hypothyroidism, diabetes mellitus, chronic obstructive pulmonary disease [COPD], cardiovascular disease, etc.) and psychological conditions (e.g., anxiety, depression, sleep disorders, etc.) also need to be considered. In our opinion, decreased physical activity may also be a factor leading to fatigue. Furthermore, anti-cancer treatments such as chemotherapy, targeted therapies, radiotherapy or surgery and other commonly prescribed medications (e.g., opioids, psychiatric drugs, antihistamines, beta blockers, and corticosteroids) are all associated with side effects that may result in fatigue.


Fig. 1 Aetiology of cancer-related fatigue.

As management of CRF is currently sub-optimal, ideally a change of approach is required, where fatigue is treated as central to patient management both during and after systemic anti-cancer treatment. The ultimate aim would be to develop a management programme including information and tools relevant to the screening, diagnosis and potential treatments/interventions for CRF, and combine these onto one platform for use by the wider oncology community. Various programmes and management tools are already available locally, which could perhaps guide best practice more widely. For example, is a website produced by the Comprehensive Cancer Centre in The Netherlands (IKNL), which facilitates the development, implementation and evaluation of guidelines for oncological and palliative care. This comprehensive site includes guidelines on the diagnosis and treatment of patients with various tumour types. It also contains guidelines for the diagnosis and treatment of many symptoms and health complaints caused by the disease itself or its treatment – including fatigue.

Integrated management of CRF

In this section we will overview key factors involved in the screening, diagnosis and treatment of cancer patients experiencing fatigue. We also suggest an algorithm for the process of managing CRF in clinical practice ( Fig. 2 ), which has been guided by our experiences in The Netherlands. This includes key stages involved in the screening and diagnosis of fatigue in patients undergoing anti-cancer therapy, as well as some of the potential treatment options. Further details relevant to each part of this algorithm are provided below.


Fig. 2 Suggested algorithm for managing fatigue in cancer patients.

Screening and diagnosis

To encourage patients and their families/caregivers to report CRF, education needs to be offered to both as soon as possible. This should aim to raise their awareness of the likelihood of fatigue developing, its contributing factors, effects on quality of life and the possible treatment options [9] . NCCN Clinical Practice Guidelines In Oncology (NCCN Guidelines®) recommend that all cancer patients should be screened for fatigue at their initial clinical visit, and then regularly during and after their anti-cancer treatment has ceased [9] . It should be noted, however, that a patient’s perception or internal standard for determining their level of fatigue can change as a result of receiving radio- or chemotherapy (the so-called ‘response shift’) and this can complicate the comparison of fatigue scores over the course of treatment [19] . For example, what might have been perceived as ‘severe fatigue’ before anti-cancer treatment commences might be noted as ‘slight fatigue’ after the patient has experienced exhaustion during treatment. This has led to some investigators advocating the use of ‘then’ ratings, where a patient indicates in retrospect after their treatment how they functioned before treatment [20] .

Many screening tools are available for CRF but most are not validated. The Distress Thermometer Screening Tool ( Fig. 3 ) is a general screening tool included in the NCCN Guidelines® for Distress Management [21] . It is often used to assess various aspects of physical and psychological distress (including fatigue), as well as other practical problems (e.g., financial burden), in oncology patients before, during and after systemic anti-cancer treatment. This questionnaire was developed [21] and validated [22] in the USA, before subsequently being adapted for use in The Netherlands [23] . As this is quite a broad-ranging instrument, it is a good initial screening tool, allowing the identification of patients requiring additional psychosocial/medical support who may be missed should a more specific questionnaire be utilised. Because of their close involvement in patient management, it may be useful to train oncology nurses to use instruments like the distress thermometer in clinical practice, as is advised in the current Dutch guidelines [24] .


Fig. 3 An example of a general screening tool for psychosocial, physical and practical issues in cancer patients: the distress thermometer.21 Reproduced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Distress Management V.2.2013. © 2013 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and illustrations herein may not be reproduced in any form for any purpose without the express written permission of the NCCN. To view the most recent and complete version of the NCCN Guidelines, go online to . NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, NCCN GUIDELINES®, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc.

If on initial screening a patient is found to have very mild (or no) fatigue, beyond providing them with education about CRF and performing regular rescreening, further clinical intervention may not be required. If, however, significant fatigue is found to be present, a quantitative or semi-quantitative assessment of its intensity should be performed. This can be done using either a uni-dimensional (e.g., the Visual Analogue Fatigue Scale [VAFS] [25] or Brief Fatigue Inventory [BFI] [26] ) or a multi-dimensional tool (e.g., the Multidimensional Fatigue Inventory [MFI [27] ], Functional Assessment of Cancer Therapy-Fatigue scale [FACT-F] [28] or Checklist Individual Strength [CIS] [29] and [30]). A detailed discussion of the available measures for the assessment of CRF is beyond the scope of this article but can be found in Jean-Pierre et al. [31] . Abbreviated, local language versions of these tools, such as the Dutch Fatigue Scale [32] and the short fatigue questionnaire [33] and [34], are also available, if needed. The short fatigue questionnaire is a validated tool developed in The Netherlands that might be particularly useful if lack of time is an issue as it consists of just four questions (‘I feel tired’, ‘I am easily tired’, ‘I feel fit’ and ‘I feel physically exhausted’), which are rated by the patient using a 7-point scale.

Focussed evaluation of likely causes of CRF and options for clinical intervention

If moderate or severe fatigue is identified, a more focussed evaluation is required to identify any contributing factors and guide potential interventions [9] and [17]. This should involve taking a thorough medical history, including the patient’s current disease status, type and length of treatment, their response to such treatment, onset and duration of fatigue, and any changes in fatigue or associated factors/symptoms over time. A review of the patient’s current medications is recommended as these may interact or cause side effects that might impact on fatigue levels. The patient’s weight should be measured alongside a discussion around their level of appetite and diet/nutritional status. A thorough physical examination should also be conducted to determine if any symptoms are related to recurrence/progression of the malignancy and a review of the body systems may be useful in identifying the systems involved and in directing the specifics of the diagnostic work-up.

During the diagnostic process it is important to identify any potentially treatable factors that could have contributed to the development of CRF, such as anaemia, pain, emotional distress, sleep disturbance, medication side effects, and comorbidities ( Fig. 1 ). Fatigue generally increases as the cancer progresses and some causative factors are more likely to be found in patients who are close to the end of life [9] . For example, at this stage there is an increased likelihood that fatigue is associated with anaemia, medication adverse events, cognitive impairment and malnutrition [9] .

Depending on the cause(s) of the fatigue, there are many possible interventions that could be used both during and after the patient’s anti-cancer treatment. Both pharmacological and non-pharmacological approaches can significantly improve patient quality of life [35], [36], [37], [38], [39], [40], and [41]. Consequently, many national and international guidelines have been released regarding the management of fatigue and causal factors such as anaemia [9], [24], [42], [43], [44], [45], and [46]. Several CRF guidelines also recommend optimising the treatment of accompanying symptoms, however, evidence from randomised trials to support this recommendation have been lacking [47] . Interestingly, a recent randomised trial demonstrated that nurse-led monitoring and protocolised treatment of physical symptoms was more effective than usual care in patients with advanced cancer and CRF [47] .

The NCCN Guidelines for CRF [9] , state that although the patient’s clinical status (i.e. whether they are undergoing active treatment, are post-treatment/receiving no active treatment except for hormonal agents, or end of life) will influence CRF management, some more general guidelines apply across all clinical categories. As there is a lack of published data on the effectiveness of specific CRF interventions in defined clinical settings (e.g., in patients undergoing curative vs. palliative chemotherapy), interventions that are likely to be useful across a spectrum of patients are the focus of this paper. Summaries of the available pharmacological and non-pharmacological approaches are shown in Table 1 and Table 2, respectively. As fatigue is a multifactorial condition, a combination of approaches is likely to be the best option for most patients.

Table 1 Examples of possible pharmacological interventions for use in cancer patients experiencing fatigue.

Cause of fatigue Possible interventions
Tumour Systemic anti-cancer therapy (e.g., chemotherapy, hormonal therapy or targeted therapy)
Anti-cancer treatment Consider reducing/delaying dose or stopping treatment (only if severe)
Other medications Consider reducing dose/withdrawal of potential fatigue-inducing drugs (e.g., psychotropic drugs, anti-histamines, beta blockers, etc.)
Anaemia If iron, folic acid or vitamin B12 levels are low, use supplements (oral/intravenous) as appropriateIf haemoglobin levels are low consider erythropoiesis-stimulating agents or whole blood/red blood cell transfusion
Electrolyte disorders Hypercalcemia: intravenous sodium chloride and bisphosphonates

Hyponatremia: fluid restriction and/or salt supplementation (oral/intravenous)
Dehydration Rehydration with intravenous sodium chloride and depending on cause could include for example, discontinuation of diuretics, initiation of insulin treatment (if hyperglycemic), and treatments for fever/excessive sweating (e.g., clonidine, progestins, selective serotonin reuptake inhibitors, gabapentin if related to hot flushes)
Weight loss If there are metabolic abnormalities resulting from anorexia-cachexia syndrome consider megestrol acetate or corticosteroids (depending on life expectancy)
Comorbidity Depends on comorbidity present; check for hypothyroidism, adrenal insufficiency, diabetes mellitus, heart failure, cardiovascular disease, COPD, infections, etc., and treat according to findings
Depression Consider use of selective serotonin reuptake inhibitors
Sleep disorders Consider short-term short-acting benzodiazepine treatment if severe or unresponsive to non-pharmacological intervention. Sedating anti-histamines, antidepressants or antipsychotics may also be useful. Melatonin or methylphenidate may be beneficial if there is a disturbed day/night-time rhythm
Underlying symptoms Pain or dyspnoea can cause fatigue and should be treated appropriately (e.g., non-steroidal anti-inflammatory drugs or opioids for pain, and morphine, corticosteroids, bronchodilators or sedatives/anxiolytics for dyspnoea)
Unknown Psychostimulants (e.g., dexamphetamine, [dexa-]methylphenidate or modafanil) for symptomatic relief

Table 2 Examples of possible non-pharmacological interventions for use in cancer patients experiencing fatigue.

Energy conservation Help patients to find a daily routine that balances activity and rest, which works for them based on their pattern of fatigue
Psychosocial support This could include counselling/psychotherapy, cognitive behavioural therapy, etc. Can be provided in the form of group therapy as part of rehabilitation programmes or individually. Can also be sought through professional psychosocial oncology centres or through psychologists, counsellors, etc. Inform patient about the possibility of spiritual care. Advise distraction (e.g., reading listening to music, walking, gardening, etc.), if appropriate to patient
Sleep therapy Stimulus control, sleep restriction and sleep hygiene may be beneficial
Complementary therapies Relaxation therapy, massage, music, herbal remedies (e.g. American ginseng), yoga, and acupuncture may also provide relief
Other supportive care Consultation with a dietician, physiotherapist or occupational therapist as required

Assist patient in gaining additional help at home from caregivers, volunteers, etc
Physical activity Encourage physical activity and provide information on any available training and/or rehabilitation programmes (supervised by a physiotherapist if fatigue is severe)
Self efficacy and self management Encourage positive patient factors such as self efficacy, mastery and learned resourcefulness

Options for pharmacological intervention

Potential pharmacological interventions for CRF are likely to include those aiming to correct any identified contributing factors impacting on fatigue ( Table 1 ). For example, adjusting the anti-cancer treatment or dose could be useful if the CRF was thought to be related to the tumour itself or its treatment. It could be beneficial to prescribe erythropoiesis-stimulating agents (ESAs) for patients with symptomatic anaemia to correct and maintain haemoglobin levels [39], [48], and [49], or for patients to receive blood transfusions to temporarily relieve the symptoms of severe anaemia [50] . It should be noted, however, that the suitability of ESAs in patients undergoing potentially curative anti-cancer therapy is still under discussion in some countries including in The Netherlands – with these agents being used more commonly in the palliative setting. Oral/intravenous iron could also be useful for patients with low iron levels [51] . All of these options have been shown to positively impact on either fatigue levels or quality or life in cancer patients with low haemoglobin levels and/or anaemia [39], [48], [49], and [51].

For other tumour-related factors such as hypercalcaemia [24] and [41], hyponatraemia or dehydration [24] prescribing bisphosphonates or fluids/fluid restriction, respectively, could be the best course of action. Megestrol acetate (Par Pharmaceuticals Inc., Spring Valley, NY, USA) or corticosteroids can also be considered for patients experiencing any metabolic abnormalities resulting from anorexia-cachexia syndrome. The choice between these treatments depends on the life expectancy of the patient (megestrol may be appropriate for those with a life-expectancy of several months or more, corticosteroids for those with a life-expectancy less than this) [24] .

Sleep disturbance often occurs in cancer patients and can impact on fatigue levels [52] . Short-term, short-acting benzodiazepine treatment may be indicated in patients with severe sleep disorders or those whose sleep problems are unresponsive to non-pharmacological intervention [24] . Sedating anti-histamines, antidepressants (e.g. amitriptyline [Actavis UK Ltd. Barnstaple, Devon, UK]) or antipsychotics may also be useful to this end. Melatonin (RAD Neurim Pharmaceuticals EEC Ltd., Reading, Berkshire, UK) or methylphenidate (Novartis Pharma, East Hanover, NJ, USA) can also be beneficial if there is a disturbed circadian rhythm [17], [24], and [53].

Other potentially useful pharmacological interventions include medications for any specific comorbidities that have been identified. This might include prescribing or adjusting treatments for hypothyroidism, adrenal insufficiency, diabetes mellitus, cardiovascular disease, COPD, etc. [9] and [24]. Depression and fatigue are also often associated in patients with cancer and so antidepressants, such as selective serotonin reuptake inhibitors, may be beneficial in some patients – although there is little evidence for a direct impact on fatigue levels [41] .

If fatigue persists after all the identified contributing factors amenable to pharmacological intervention have been addressed, further action could be indicated to manage symptoms. This could include prescription of non-steroidal anti-inflammatory drugs or opioids for patients experiencing pain, and morphine, corticosteroids, bronchodilators or sedatives/anxiolytics for those experiencing dyspnoea [24] . Psychostimulants (e.g. [dexa-]methylphenidate [Novartis Pharma, East Hanover, NJ, USA], dexamphetamine [Amedra Pharmaceuticals LLC, Horsham, PA, USA] or modafanil [Cephalon Inc., Frazer, PA, USA]) have also shown some efficacy in relieving fatigue in randomised and open-label trials [53], [54], and [55].

Options for non-pharmacological intervention

Several non-pharmacological approaches have been shown to be effective for relieving or managing fatigue in patients with cancer ( Table 2 ) and these can be used alongside the pharmacological interventions described above. Such approaches could also be useful in patients not benefitting from or amenable to pharmacological treatments, such as those with mild symptoms, and those where no treatable causative factors for CRF have been identified. Energy conservation can be a useful, common-sense, strategy for all cancer patients, helping them to prioritise, pace and delegate activities to prevent energy depletion. Daily self-monitoring of fatigue levels may also help patients to find a routine balancing activity and rest, which works best for them based on their pattern of fatigue [9] .

If a patient is experiencing difficulties with sleeping, various behavioural techniques can be recommended for improving sleep patterns. These include stimulus control (where patients are advised to go to bed when sleepy and have routine times for going to bed and rising in the morning), sleep restriction (avoidance of long daytime naps and limiting time in bed), and sleep hygiene (avoiding caffeine and exercise near bedtime and having comfortable sleep surroundings) [17] . Complementary therapies may also have a role for improving sleep disorders and other conditions. For example, relaxation techniques and massage may aid sleep and decrease distress/anxiety, while yoga, acupuncture and American ginseng have all shown some evidence of relieving CRF [9], [17], [56], and [57]. Some patients experiencing CRF may benefit from additional supportive care. Depending on their individual needs, this might include consulting with other more specialised healthcare professionals such as dieticians, physiotherapists, or occupational therapists [9] and [24]. It might also be beneficial to assist the patient in gaining additional help at home from caregivers, volunteers, or from the use of labour-saving devices.

It is important to offer psychosocial support to patients showing symptoms of psychological burden/distress [14], [58], and [59]. This could take many forms, for example, stress management techniques, use of support groups, counselling/psychotherapy on an individual basis, or spiritual care. The use of distraction (i.e. activities such as playing games, music, reading, and socialising, which are designed to distract the patient from their condition), may also be helpful [17] . Cognitive behavioural therapy (CBT) could also have a role to play, as it is not only effective in relieving fatigue in patients with cancer [60] and [61], but may also lead to a decline in perceived cognitive disability and a reduction in concentration problems [62] . In line with this, patients reporting concentration and memory problems before initiation of anticancer therapy seem to benefit most from CBT, with improvements lasting up to 7 months post intervention [63] . In the author’s opinion, patients should be offered CBT during or in the first 12 months after receiving their anticancer therapy.

The side effects of anti-cancer therapy can lead to a reduction in the patient’s physical activity and performance [9] . Conversely, several clinical studies and meta-analyses have shown the benefits of increased physical activity/exercise on CRF, physical/emotional functioning, insomnia and overall quality of life [43], [64], [65], and [66]. Benefits have even been observed in patients with advanced cancer [65] . Exercise may also enhance fitness and minimise the likelihood of the patient developing fatigue or of it worsening. Interestingly, it has been suggested that CBT offers no additional benefit over that seen with physical exercise alone [67] . However, results have been somewhat conflicting with a second randomised trial unexpectedly reporting that the benefits of CBT in patients with CRF were not mediated by increased physical activity [60] . At present we cannot draw firm conclusions regarding the separate and/or cumulative effects of CBT and physical exercise, but trials are ongoing in this area. For instance, the TIRED (Treatment of fatigue duRingpalliativE care of advanced or metastatic Disease) trial is assessing the benefits of exercise, CBT and usual care on fatigue in patients with advanced/metastatic breast or colon cancer [68] . Two additional randomised trials are assessing the impact of various forms of exercise in patients with non-metastatic colon or breast cancer receiving adjuvant chemotherapy. The Physical Activity during Cancer Treatment (PACT) trial is comparing fatigue levels between patients undergoing an 18-week, physiotherapist-supervised physical training/exercise programme and control patients not undertaking this programme [69] . Whereas, the Physical exercise during Adjuvant Chemotherapy Effectiveness Study (PACES) is evaluating the effectiveness of a low/moderate intensity, home-based, self-managed physical activity programme (Onco-Move) and a relatively high-intensity, structured, supervised outpatient exercise programme (OnTrack) [70] .

Although the results of such trials are awaited, it now seems reasonable to encourage cancer patients to engage in moderate physical activity during and after anti-cancer treatment [9] . The optimum amount or type of activity is yet to be determined but could include anything from a general avoidance of inactivity and an increase in activity level in the home, to supervised outpatient exercise/training programmes. The type and frequency of exercise can be customised to meet the requirements of each patient but exercise should be used with caution in those with bone metastases, thrombocytopaenia, anaemia or fever/active infection [9] . The American College of Sports Medicine has recently published exercise guidelines for cancer survivors with specific exercise programming adaptations based on disease and treatment-related adverse effects [43] .

We should also note that various patient- (and also caregiver-) related factors such as perceived self efficacy, mastery, optimism and learned resourcefulness have been reported to influence CRF levels [71], [72], [73], [74], [75], and [76]. It is, therefore, important for healthcare providers to recognise and encourage such traits to help patients more effectively manage their symptoms. Patient education can help improve self efficacy [77] and an ongoing trial (RESTORE) may help identify whether an online or leaflet-based approach is most effective [78] . The beneficial effects of exercise on CRF may in some part be mediated by self efficacy and mastery [79], [80], [81], and [82], and conversely, interventions that improve self efficacy have also been shown to improve physical activity, and thereby relieve fatigue [83] and [84].

Barriers to the effective management of CRF

Despite the existence of multiple treatment guidelines, these are often not followed and in daily clinical practice CRF is not optimally dealt with, often remaining unrecognised and untreated [9] and [85]. For example, in a recent study only about half of patients with severe cancer-related anaemia and fatigue received treatment with epoetin and/or blood transfusion in accordance with clinical practice guidelines [85] . Barriers to effective CRF management exist both on the side of the treating physician and their patients [86] . For example, there may be a lack of awareness by physicians or they may feel uncomfortable discussing CRF because they feel they have a lack of knowledge in this area or are concerned about the limited treatment options. Furthermore, physicians may underestimate the severity or frequency of a patient’s symptoms including fatigue [87] and may also fail to appreciate the impact of CRF on a patient’s quality of life [17] and [88], Differences can exist between the patient’s and their healthcare provider’s estimation of fatigue and overall quality of life [89] . Many patients regard fatigue as having a greater negative impact on their daily lives than many other cancer- or treatment-related complications [18] . In contrast, physicians often believe that pain adversely affects their cancer patients more than fatigue [90] . Furthermore, the patient’s family members/caregivers may overestimate the impact of patient symptoms [87] .

System barriers such as time constraints might also exist limiting the opportunity for discussion between physician and patient. For instance, guidance in The Netherlands suggests that physicians should ideally spend approximately 15 min with each patient at each standard follow-up visit after their initial consultation [91] . In addition, patients may consider CRF to be an unavoidable consequence of their disease or treatment and therefore may avoid mentioning it as a symptom because they do not want to be perceived as complaining. The fear that the presence of CRF could mean that the cancer has recurred or progressed or that it might lead to a less aggressive form of anti-cancer treatment may also prevent patients from raising this as a concern [1], [15], [17], and [88]. In our experience, patients may also try their best to perform well in front of their physician even though they are struggling with fatigue in their daily life, which can make it even more difficult for physicians to recognise the scale of the problem.

Summary and conclusions

CRF remains an under-recognised and under-discussed condition, despite its deleterious impact on patient quality of life [4], [5], [15], and [16]. If we are to improve management of this condition, it is important to raise awareness about CRF in both healthcare professionals and cancer patients. To achieve successful symptom control, there is also a need for close dialogue between the patient, their caregivers and the members of the treating multidisciplinary team [87] . There are many different programmes in The Netherlands and elsewhere focussing on various aspects of CRF management (e.g., psychological, social, religious, somatic/physical aspects of this condition, etc.), but none have been completely validated and their effectiveness remains to be proven. As many factors impact on the development of CRF, we believe a multicausal and multidisciplinary approach to fatigue management in cancer patients is preferable, where all aspects are assessed and treated together. With this in mind, it is hoped that the suggested algorithm ( Fig. 2 ) could provide a useful tool to healthcare professionals dealing with cancer patients in their daily practice, as it should guide them through the key stages involved in the screening, diagnosis and treatment of CRF, and thereby improve its management. Although fatigue is a serious and complex clinical problem, it is important to work through it in a structured and comprehensive way as effective management has the potential to much improve patient quality of life.

Conflicts of interest

R.H.T. Koornstra: membership of a focus group on fatigue management, founded by Amgen and a member of advisory boards for Amgen (but none on this subject). M.E.W.J. Peters: membership of a focus group on fatigue management, founded by Amgen. S.M. Donofrio: membership of a focus group on fatigue management, founded by Amgen. B. van den Borne: membership of a focus group on fatigue management, founded by Amgen. F.A. de Jong: during initiation of this manuscript FdJ was an employee of Amgen BV, Breda, The Netherlands; he also holds Amgen stock.


Dawn Batty PhD from BioscriptMedical Ltd. provided medical writing assistance (funded by Amgen BV).


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a Radboud University Medical Center, Nijmegen, The Netherlands

b University of Groningen, Groningen, The Netherlands

c Catharina Hospital, Eindhoven, The Netherlands

d Amgen BV, Breda, The Netherlands

lowast Corresponding author. Address: Radboud University Medical Center, Department of Medical Oncology, PO Box 9101 (intern nr 452), 6500 HB Nijmegen, The Netherlands. Tel.: +31 (0)24 3610 353; fax: +31 (0)24 3540 788.

1 Address: Radboud University Medical Center, Department of Medical Oncology, PO Box 9101 (intern nr 452), 6500 HB Nijmegen, The Netherlands. Tel.: +31 (0)24 3610 353; fax: +31 (0)24 3540 788.

2 Address: Department of Psychology, University of Groningen, Grote Kruisstraat 2/1, 9712 TS Groningen, The Netherlands. Tel.: +31 (0)50 3637 034; fax: +31 (0)50 3636 304.

3 Address: Catharina Hospital, Department of Pulmonology, Michelangelolaan 2, 5623 EJ Eindhoven, The Netherlands. Tel.: +31 (0)40 2397 280; fax: +31 (0)40 2399 111.

4 Address: Merck KGaA, Merck Serono Division, HQ Medical Affairs, Mail code F133/302, Frankfurter Strasse 250, 64293 Darmstadt, Germany. Tel.: +49 (0)6151 725 5191; fax: +49 (0)6151 726 1781.

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