Indian Journal of Palliative Care
Open access journal 
  Print this page Email this page   Small font sizeDefault font sizeIncrease font size Users online: 6  
     Home | About | Feedback | Login 
  Current Issue Back Issues Editorial Board Authors and Reviewers How to Subscribe Advertise with us Contact Us Analgesic Prescription  
  Navigate Here 
 Search
 
  
 Resource Links
  »  Similar in PUBMED
 »  Search Pubmed for
 »  Search in Google Scholar for
 »Related articles
  »  Article in PDF (483 KB)
  »  Citation Manager
  »  Access Statistics
  »  Reader Comments
  »  Email Alert *
  »  Add to My List *
* Registration required (free)  

 
  In this Article
 »  Abstract
 » Introduction
 » Epidemiology
 »  Fatigue Assessme...
 »  Anticipation and...
 » Conclusion
 »  References
 »  Article Tables

 Article Access Statistics
    Viewed2137    
    Printed172    
    Emailed0    
    PDF Downloaded198    
    Comments [Add]    

Recommend this journal

 


 
Table of Contents 
REVIEW ARTICLE
Year : 2011  |  Volume : 17  |  Issue : 2  |  Page : 92-97

Evaluation and management of fatigue in oncology: A multidimensional approach


Department of Medical Oncology, National Institute of Oncology, Rabat, Morocco

Date of Web Publication5-Sep-2011

Correspondence Address:
El Mehdi Tazi
Department of Medical Oncology, National Institute of Oncology, Rabat
Morocco
Login to access the Email id


DOI: 10.4103/0973-1075.84528

PMID: 21976847

Get Permissions

 » Abstract 

Fatigue, one of the most common symptoms experienced by cancer patients, is multidimensional and is associated with significant impairment in functioning and overall quality of life. Although the precise pathophysiology of cancer-related fatigue (CRF) is not well understood, a number of metabolic, cytokine, neurophysiologic, and endocrine changes have been described in these patients. A better understanding of these abnormalities is likely to lead to novel therapeutic interventions. Clinically, all patients presenting with significant fatigue should be evaluated for treatable conditions that might contribute to this symptom. Exercise and treatment of anemia are the two most established interventions for CRF. Psychostimulants seem promising based on early studies. Several complementary medicine treatments that showed efficacy in preliminary studies merit further testing.


Keywords: Fatigue, Multidimensional approach, Oncology


How to cite this article:
Tazi E, Errihani H. Evaluation and management of fatigue in oncology: A multidimensional approach. Indian J Palliat Care 2011;17:92-7

How to cite this URL:
Tazi E, Errihani H. Evaluation and management of fatigue in oncology: A multidimensional approach. Indian J Palliat Care [serial online] 2011 [cited 2014 Aug 28];17:92-7. Available from: http://www.jpalliativecare.com/text.asp?2011/17/2/92/84528



 » Introduction Top


The National Comprehensive Cancer Network (NCCN) defines cancer-related fatigue (CRF) as "a persistent, subjective sense of tiredness related to cancer or cancer treatment that interferes with usual functioning." [1] These symptoms are persistent, disproportionate to the level of exertion, and typically not relieved by rest. The criteria of NCCN for the diagnosis of CRF have been accepted by the International Classification of Diseases (ICD, 10 th revision, clinical modification). [2] CRF is underrecognized and undertreated, partly because of limited understanding of its pathophysiology and lack of effective treatments. With better treatments available for cancer-related pain, nausea, and vomiting, increasing attention is being paid to CRF. In this review, we present the current understanding of the clinical significance, pathophysiology, and management of CRF.


 » Epidemiology Top


Prevalence

Fatigue is one of the most common symptoms experienced by cancer patients. The prevalence of self-reported fatigue in these patients ranges from 17% to 95% in different studies. [3],[4],[5] This wide range partly reflects heterogeneity in different studies in terms of the definition of fatigue, stage of tumor, and use of adjuvant therapy. The prevalence of fatigue was only 17% when the most stringent diagnostic criteria were used. [5] Most patients with advanced-stage tumor have significant fatigue. A higher proportion of patients receiving chemotherapy, radiotherapy, biologic response modifiers, or autologous transplantation develop fatigue compared with patients who do not receive these treatments. [6],[7],[8]

Impact on quality of life

Fatigue has a significant impact on the overall quality of life. In the Fatigue-1 study, of the 419 patients with cancer who participated in a telephone interview, 78% experienced fatigue during the course of their treatment. [9] Fatigue adversely affected patients in their daily lives more than did pain (61% vs. 19%). Specific treatment for fatigue was recommended by oncologists for only 23% of the patients. The Fatigue-2 study involved a telephone survey of 379 patients with cancer who had previously received chemotherapy. [7] Seventy-six percent of the patients reported experiencing significant fatigue at least a few days each month during their most recent chemotherapy cycle, with 30% experiencing daily fatigue. Most patients noted that when they experienced fatigue, they were unable to lead a "normal" life (91%) or had alteration in their daily routine (88%) because of fatigue. The treatment that patients said was most often recommended to them by their physicians was bed rest/relaxation (37%). However, data collected in both these studies were retrospective and, thus, increased the possibility of recall bias. Presence of ongoing fatigue is associated with greater symptom distress and worse performance status and is a prognostic factor associated with overall survival in univariate but not multivariate models. [10],[11]

Fatigue trajectory

Fatigue symptoms fluctuate over the course of the cancer. In patients receiving chemotherapy, fatigue is generally worst 4-5 days after receiving chemotherapy or at the nadir of cell counts in patients who develop significant myelosuppression. [6],[12] With radiotherapy, the severity of fatigue usually peaks at the end of treatment and improves over the next 3-6 months. [13],[14] However, fatigue may persist for years after completing treatment, even while patients are in complete remission. [15]

Pathophysiology

The precise pathophysiology of CRF is not well understood. Subjectivity in fatigue assessment, the multidimensional component of fatigue, and the lack of an animal model contribute to this limitation. Several metabolic, cytokine, neurophysiologic, and endocrine changes associated with fatigue have been described.

Medical conditions contributing to fatigue

A number of treatable conditions that are common in cancer patients can contribute to fatigue [Table 1]. [1] Psychosocial conditions that predispose to fatigue include the presence of anxiety and depression, inadequate coping skills, and a lack of social support. Other associations of significant fatigue include female gender, higher cancer stage, smaller size of household, higher education level, and full-time employment status. [16]
Table 1: Medical and psychosocial conditions associated with cancer-related fatigue

Click here to view


Cytokine changes

Cancer is associated with the release of several cytokines. These include interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α.[17] Injection of these cytokines in laboratory animals has been shown to induce anorexia, weight loss, and social withdrawal. [18] In an observational study of 40 patients with breast cancer, including 20 who reported fatigue and 20 without fatigue, significantly higher levels of proinflammatory cytokines were demonstrated in patients who reported fatigue. [17] The elevated cytokines included IL-1 receptor antagonist, soluble TNF receptor type II, and neopterin.

Neuromuscular abnormalities

Fatigue is associated with several abnormalities in skeletal muscle structure and function. In patients with advanced gastric cancer, an increase in skeletal muscle protein breakdown was shown without a significant change in total body protein turnover. [19] Some of the other reported abnormalities include increased resting energy consumption, impaired muscle protein synthesis, abnormalities in adenosine triphosphate (ATP) generation, and intracellular calcium flux. Neurologic changes described with CRF include an overall diminished activation from the central nervous system and reduced neuromuscular efficiency. [20]

Some chemotherapeutic agents, such as vincristine, cisplatin, and paclitaxel, are also directly neurotoxic and thus might cause fatigue through this mechanism.

Neuroendocrine changes

Several endocrine changes are described in patients with CRF. The search for a central endocrine abnormality leading to CRF is enticing because a representative model might lead to a direct and simple therapeutic intervention. However, the present models lack specificity and, although the abnormalities related to fatigue are reasonably well described, it is not clear whether the changes observed are causative for CRF or mere associations. Dysfunctions of the hypothalamic-pituitary-adrenal axis (HPA) are described in patients with CRF and in chronic fatigue syndrome. These include decreased steroid output, lower levels of gonadotropins and androgens, and reduced HPA function on neuroendocrine challenge tests. [21] An elevation in proinflammatory cytokines (in turn stimulated by interferon-α and IL-2) affects the HPA function, leading to a reduction in cortisol output. Another intriguing model relates to the importance of disruption of the circadian rhythms in CRF.[21] Most biologic functions of humans have a circadian rhythm. These include endogenous steroid production, melatonin secretion, sleep-wake cycle, and temperature regulation, among others. A disruption of circadian rhythms is reported to cause sleep disturbance, depression, anorexia, and, possibly, fatigue. However, the current evidence behind the circadian rhythms being the central abnormality leading to fatigue is not conclusive. In attempts to find a common underlying mechanism for the development of CRF, several disease models have been developed. [21],[22] Four such hypotheses are described in a recent review: the anemia hypothesis, the ATP hypothesis, the vagal afferent hypothesis, and the HPA-pituitary axis, cytokine, and 5HT (serotonin dysregulation) hypothesis. [22] However, none of these models fully describes all the dimensions of fatigue. Thus, much work remains to be done in this field.


 » Fatigue Assessment in Patients with Cancer Top


Because patients may not self-report fatigue, they should be actively screened for symptoms consistent with CRF. Most patients with CRF should be appropriately evaluated. This evaluation should include assessment of fatigue symptoms (severity, duration, time course, and exacerbating and relieving factors), evaluation of potentially reversible conditions [Table 1], assessment of the effect of fatigue on quality of life and performance status, and evaluation of symptoms commonly associated with fatigue. A number of validated scales have been developed to measure fatigue severity. [23] The Brief Fatigue Inventory (BFI) is one of the most simple instruments that can be used in clinical and research settings. [24] Fatigue severity is scored from 0 to 10, with mild fatigue being 1 to 3, moderate 4 to 6, and severe 7 to 10.

Management

The NCCN and the Fatigue Coalition have developed guidelines and algorithms for the management of patients with CRF. [1],[2] The focus is to identify and treat underlying reversible conditions with a broad array of pharmacologic and non-pharmacologic treatments, recognizing the multidimensional aspects of fatigue. In general, patients with mild fatigue (BFI 1-3) should continue to be closely observed with an effort at anticipating and preventing the development of more severe fatigue. For patients with moderate or severe fatigue, further evaluation and management is recommended.

Treatment of fatigue

Few interventions have demonstrated a benefit for the treatment of fatigue in the absence of a reversible condition. Individual interventions and the levels of evidence behind their use are discussed in the following paragraphs.

Treatment of anemia

Anemia is a common reversible cause of fatigue in patients with cancer. Several causes of anemia are recognized in these patients, including hemorrhage, hemolysis, nutritional deficiencies, bone marrow infiltration, cytokine-mediated problems, anemia related to chemotherapy or radiotherapy, and anemia of chronic disease. Once specific deficiencies and other reversible causes are excluded, treatment of anemia with erythropoietin-α or darbepoetin-α was shown to improve fatigue in four well-designed randomized double-blind clinical trials. [25],[26],[27],[28] In general, maximal benefit is observed at a target hemoglobin range of 11-13 g/dL.

Exercise

Most exercise programs have been shown to improve fatigue and other symptoms, including functional capacity and overall quality of life. Forms of exercise that have been tested and found efficacious in randomized controlled trials include cycle ergometers, [29],[30] walking, [31],[32],[33],[34],[35],[36] resistance training, [37] and exercise of choice. [38],[39],[40] Exercise is also reported to have a beneficial effect on functional capacity following anticancer therapy. [33] Exercise should ideally be prescribed to prevent the development of fatigue because patients with moderate to severe fatigue are likely to find it difficult to start an exercise program. Most studies testing exercise were designed as preventive trials. [30],[31],[32],[33],[34],[36],[39] Furthermore, the evidence for the efficacy of exercise in patients with advanced disease is limited. [41]

Psychosocial interventions

Several types of psychosocial intervention have been found to be beneficial in CRF. A 6-week program of structured psychiatric intervention (health education, enhancement of problem-solving skills, stress management, and psychological support) improved depression, fatigue, confusion, and total mood disturbance at 6 months in patients with malignant melanoma. [41],[42] Similar improvement was seen in a follow-up study that was designed as a randomized trial. [43] In another randomized trial, in patients about to start chemotherapy, self-administered stress management training was reported to be superior to professional training or no intervention. [44] Group support was reported to improve mood states and coping response in a randomized trial in patients with metastatic breast cancer. [45] A comprehensive coping strategy program comprised of preparatory information, cognitive restructuring, and relaxation with guided imagery improved nausea and fatigue in a randomized trial in women with breast cancer undergoing autologous stem cell transplantation. [46] Other interventions reported to be efficacious for improving fatigue symptom severity include psychotherapy and tailored behavioral intervention. [41]

Drugs

Pharmacologic agents tested for CRF include psychostimulants, progestational agents, and corticosteroids [Table 2]. Two open-label clinical trials reported on the effect of methylphenidate for CRF. In the larger study involving 31 patients, methylphenidate use was reported to be efficacious in improving fatigue in patients with advanced cancer. [47] Patients' fatigue improved significantly from a Functional Assessment for Chronic Illness Therapy-Fatigue (FACIT-F) score of 7.2 ± 1.6 to 3.0 ± 1.9 after 7 days of treatment. In the other open-label study, which involved 11 patients with advanced cancer, methylphenidate intake was associated with improved fatigue from moderate to severe, to mild in nine patients within 3 days. [48] Methylphenidate also improved fatigue measured by the Edmonton Symptom Assessment System (ESAS) in a more rigorously designed randomized trial in patients with human immunodeficiency virus infection. [49] Results of a more definitive study of methylphenidate for CRF in a double-blind randomized controlled trial are awaited. Two additional psychostimulants have been tested for the treatment of fatigue in chronically ill patients. Modafinil was considered to be efficacious in improving fatigue in a single-arm study in patients with multiple sclerosis. [49],[50] Many other pharmacologic treatments have been examined for CRF. Corticosteroids were shown to cause decreased depression and analgesic consumption and increased appetite and daily activity in a small, randomized placebo-controlled trial of a 14-day course of oral methylprednisolone in terminally ill cancer patients. However, no larger trials involving longer courses of corticosteroids in other populations have been carried out. Trials have also failed to show any benefit of dextroamphetamine, [51] multivitamins, [52] or antidepressants. [53] In a meta-analysis, neither progestational steroids nor paroxetine were found to be better than placebo in the treatment of CRF. [54] Finally, in a Cochrane systematic review published in 2008 and updated in 2010, no clinically meaningful benefit was found for agents other than psychostimulants in the pharmacologic treatment of CRF. [55]
Table 2: Drugs commonly used for the treatment of cancer-related fatigue

Click here to view


Complementary and alternative medicine

A reductionistic approach to treatment of CRF may not work for most patients. Fatigue has an effect on the physical, social, psychological, and spiritual aspects of patients' lives, and therapeutic models encompassing all these realms are more likely to address this symptom effectively. Several alternative treatment programs, particularly the mind-body interventions, are built on such a biopsycho-socio-spiritual model. Cancer patients commonly use complementary and alternative (CAM) interventions, often without the knowledge of their treating physicians. Several CAM interventions have been tested for CRF. CAM interventions with preliminary evidence of efficacy include acupuncture, [56] energy conservation and activity management, [57] healing touch, [58] hypnosis, [59] lectin-standardized mistletoe extract, [60] levo-carnitine, [61] massage, [62] sleep promotion, [63] support groups, [41] and Tibetan yoga. [64] However, the results from these studies are not conclusive because of small sample size, methodologic limitations, and use of fatigue as a secondary endpoint.


 » Anticipation and Prevention Top


Because the treatment of established fatigue is difficult, anticipation and prevention of the development of significant fatigue is a prudent approach. Patient education is the single most important component at this stage of management. It is important to help patients understand that the development of fatigue does not necessarily imply a spread of their cancer. [1] Furthermore, it is hoped that maintenance of an optimal level of physical activity, anticipation and treatment of psychiatric disorders, and optimal management of pain and anemia will minimize the development of significant fatigue.


 » Conclusion Top


Fatigue is the most common symptom experienced by patients with cancer and is associated with worsening of functioning and overall quality of life. Fatigue is significantly underreported by patients and undertreated by physicians. The precise pathophysiology of CRF is not well understood, but it is likely to involve several related medical, neuroendocrine, cytokine, and muscular changes. All patients with significant fatigue should be evaluated for reversible medical conditions and educated about the prevalence, prevention, and management of CRF. Exercise and treatment of anemia are the two most effective interventions for CRF. Several psychosocial interventions may also be beneficial. Psychostimulants seem promising in preliminary clinical studies, but more definitive studies are needed. A number of CAM interventions have shown promise in preliminary studies and merit further testing. Clearly, more research is needed using well-designed, prospective clinical trials for better management of patients with CRF.



 
 » References Top

1.Mock V, Atkinson A, Barsevick A, Cella D, Cimprich B, Cleeland C, et al. NCCN practice guidelines for cancer-related fatigue. Oncology (Huntingt) 2000;14:151-61.  Back to cited text no. 1
    
2.Portenoy RK, Itri LM. Cancer-related fatigue: Guidelines for evaluation and management. Oncologist 1999;4:1-10.  Back to cited text no. 2
    
3.Curt GA. The impact of fatigue on patients with cancer: overview of FATIGUE 1 and 2. Oncologist 2000;2:9-12.  Back to cited text no. 3
    
4.Okuyama T, Akechi T, Kugaya A, Okamura H, Imoto S, Nakano T, et al. Factors correlated with fatigue in disease-free breast cancer patients: Application of the cancer fatigue scale. Support Care Cancer 2000;8:215-22.  Back to cited text no. 4
    
5.Cella D, Davis K, Breitbart W, Curt G. Cancer-related fatigue: Prevalence of proposed diagnostic criteria in a United States sample of cancer survivors. J Clin Oncol 2001;19:3385-91.  Back to cited text no. 5
    
6.de Jong N, Candel MJ, Schouten HC, Abu-Saad HH, Courtens AM. Prevalence and course of fatigue in breast cancer patients receiving adjuvant chemotherapy. Ann Oncol 2004;15:896-905.  Back to cited text no. 6
    
7.Curt GA, Breitbart W, Cella D, Groopman JE, Horning SJ, Itri LM, et al. Impact of cancer-related fatigue on the lives of patients: New findings from the Fatigue Coalition. Oncologist 2000l5:353-60.  Back to cited text no. 7
    
8.Jacobsen PB, Stein K. Is fatigue a long-term side effect of breast cancer treatment? Cancer Control 1999;6:256-63.  Back to cited text no. 8
    
9.Vogelzang NJ, Breitbart W, Cella D, Curt GA, Groopman JE, Horning SJ, et al. Patient, caregiver, and oncologist perceptions of cancer-related fatigue: Results of a tripart assessment survey. The Fatigue Coalition. Semin Hematol 1997;34:4-12.  Back to cited text no. 9
    
10.Chow E, Fung K, Panzarella T, Bezjak A, Danjoux C, Tannock I. A predictive model for survival in metastatic cancer patients attending an outpatient palliative radiotherapy clinic. Int J Radiat Oncol Biol Phys 2002;53:1291-302.  Back to cited text no. 10
    
11.Luoma ML, Hakamies-Blomqvist L, Sjöström J, Pluzanska A, Ottoson S, Mouridsen H, et al. Prognostic value of quality of life scores for time to progression (TTP) and overall survival time (OS) in advanced breast cancer. Eur J Cancer 2003;39:1370-6.  Back to cited text no. 11
    
12.Berger AM. Patterns of fatigue and activity and rest during adjuvant breast cancer chemotherapy. Oncol Nurs Forum 1998;25:51-62.  Back to cited text no. 12
    
13.Magnan MA, Mood DW. The effects of health state, hemoglobin, global symptom distress, mood disturbance, and treatment site on fatigue onset, duration, and distress in patients receiving radiation therapy. Oncol Nurs Forum 2003;30:E33-9.  Back to cited text no. 13
    
14.Irvine DM, Vincent L, Graydon JE, Bubela N. Fatigue in women with breast cancer receiving radiation therapy. Cancer Nurs 1998;21:127-35.  Back to cited text no. 14
    
15.Broeckel JA, Jacobsen PB, Horton J, Balducci L, Lyman GH. Characteristics and correlates of fatigue after adjuvant chemotherapy for breast cancer. J Clin Oncol 1998;16:1689-96.  Back to cited text no. 15
    
16.Akechi T, Kugaya A, Okamura H, Yamawaki S, Uchitomi Y. Fatigue and its associated factors in ambulatory cancer patients: A preliminary study. J Pain Symptom Manage 1999;17:42-8.  Back to cited text no. 16
    
17.Bower JE, Ganz PA, Aziz N, Fahey JL. Fatigue and proinflammatory cytokine activity in breast cancer survivors. Psychosom Med 2002;64:604-11.  Back to cited text no. 17
    
18.Dantzer R, Bluthé RM, Gheusi G, Cremona S, Layé S, Parnet P, et al. Molecular basis of sickness behavior. Ann N Y Acad Sci 1998;856:132-8.  Back to cited text no. 18
    
19.Dworzak F, Ferrari P, Gavazzi C, Maiorana C, Bozzetti F. Effects of cachexia due to cancer on whole body and skeletal muscle protein turnover. Cancer 1998;82:42-8.  Back to cited text no. 19
    
20.Monga U, Jaweed M, Kerrigan AJ, Lawhon L, Johnson J, Vallbona C, et al. Neuromuscular fatigue in prostate cancer patients undergoing radiation therapy. Arch Phys Med Rehabil 1997;78:961-6.  Back to cited text no. 20
    
21.Payne JK. A neuroendocrine-based regulatory fatigue model. Biol Res Nurs 2004;6:141-50.  Back to cited text no. 21
    
22.Morrow GR, Andrews PL, Hickok JT, Roscoe JA, Matteson S. Fatigue associated with cancer and its treatment. Support Care Cancer 2002;10:389-8.  Back to cited text no. 22
    
23.Ahlberg K, Ekman T, Gaston-Johansson F, Mock V. Assessment and management of cancer-related fatigue in adults. Lancet 2003;362:640-50.  Back to cited text no. 23
    
24.Mendoza TR, Wang XS, Cleeland CS, Morrissey M, Johnson BA, Wendt JK, et al. The rapid assessment of fatigue severity in cancer patients: use of the Brief Fatigue Inventory. Cancer 1999;85:1186-96.  Back to cited text no. 24
    
25.Littlewood TJ, Bajetta E, Nortier JW, Vercammen E, Rapoport B. Epoetin alfa study group. Effects of epoetin alfa on hematologic parameters and quality of life in cancer patients receiving nonplatinum chemotherapy: Results of a randomized, double-blind, placebo-controlled trial. J Clin Oncol 2001;19:2865-74.  Back to cited text no. 25
    
26.Osterborg A, Brandberg Y, Molostova V, Iosava G, Abdulkadyrov K, Hedenus M, et al. Randomized, double-blind, placebo-controlled trial of recombinant human erythropoietin, epoetin Beta, in hematologic malignancies. J Clin Oncol 2002;20:2486-94.  Back to cited text no. 26
    
27.Glaspy JA, Jadeja JS, Justice G, Kessler J, Richards D, Schwartzberg L, et al. Darbepoetin alfa given every 1 or 2 weeks alleviates anaemia associated with cancer chemotherapy. Br J Cancer 2002;87:268-76.  Back to cited text no. 27
    
28.Vansteenkiste J, Pirker R, Massuti B, Barata F, Font A, Fiegl M, et al. Double-blind, placebocontrolled, randomized phase III trial of darbepoetin alfa in lung cancer patients receiving chemotherapy. J Natl Cancer Inst 2002;94:121-20.  Back to cited text no. 28
    
29.Hilarius DL, Kloeg PH, van der Wall E, Komen M, Gundy CM, Aaronson NK. Cancer-related fatigue: Clinical practice versus practice guidelines. Support Care Cancer 2011;19:531-8.  Back to cited text no. 29
    
30.VelthuisMJ, Agasi-Idenburg SC, Aufdemkampe G, Wittink HM. The effect of physical exercise on cancer-related fatigue during cancer treatment: A meta-analysis of randomised controlled trials. Clin Oncol (R Coll Radiol) 2010;22:208-21.  Back to cited text no. 30
    
31.Thorsen L, Skovlund E, Strømme SB, Hornslien K, Dahl AA, Fossa SD. Effectiveness of physical activity on cardiorespiratory fitness and health-related quality of life in young and middleaged cancer patients shortly after chemotherapy. J Clin Oncol 2005;23:2378-88.  Back to cited text no. 31
    
32.Windsor PM, Nicol KF, Potter J. A randomized, controlled trial of aerobic exercise for treatment-related fatigue in men receiving radical external beam radiotherapy for localized prostate carcinoma. Cancer 2004;101:550-7.  Back to cited text no. 32
    
33.Griffith K, Wenzel J, Shang J, Thompson C, Stewart K, Mock V. Impact of a walking intervention on cardiorespiratory fitness, self-reported physical function, and pain in patients undergoing treatment for solid tumors. Cancer 2009;115;4874-84.  Back to cited text no. 33
    
34.Courneya KS, Sellar CM, Stevinson C, McNeely ML, Peddle CJ, Friedenreich CM, et al. Randomized controlled trial of the effects of aerobic exercise on physical functioning and quality of life in lymphoma patients. J Clin Oncol 2009;27:4605-12.  Back to cited text no. 34
    
35.Dimeo F, Schwartz S, Fietz T, Wanjura T, Böning D, Thiel E. Effects of endurance training on the physical performance of patients with haematological malignancies during chemotherapy. Support Care Cancer 2003;11:623-8.  Back to cited text no. 35
    
36.Segal RJ, Reid RD, Courneya KS, Sigal RJ, Kenny GP, Prud'Homme DG, et al. Randomized controlled trial of resistance or aerobic exercise in men receiving radiation therapy for prostate cancer. J Clin Oncol 2009;27:344-51.  Back to cited text no. 36
    
37.Segal RJ, Reid RD, Courneya KS, Malone SC, Parliament MB, Scott CG, et al. Resistance exercise in men receiving androgen deprivation therapy for prostate cancer. J Clin Oncol 2003;21:1653-9.  Back to cited text no. 37
    
38.Milne HM, Wallman KE, Gordon S, Courneya KS. Effects of a combined aerobic and resistance exercise program in breast cancer survivors: A randomized controlled trial. Breast Cancer Res Treat 2008;108:279-88.  Back to cited text no. 38
    
39.Schwartz AL, Mori M, Gao R, Nail LM, King ME. Exercise reduces daily fatigue in women with breast cancer receiving chemotherapy. Med Sci Sports Exerc 2001;33:718-23.  Back to cited text no. 39
    
40.Vallance JK, Courneya KS, Plotnikoff RC, Yasui Y, Mackey JR. Randomized controlled trial of the effects of print materials and step pedometers on physical activity and quality of life in breast cancer survivors. J Clin Oncol 2007;25:2352-9.  Back to cited text no. 40
    
41.Given C, Given B, Rahbar M, Jeon S, McCorkle R, Cimprich B, et al. Effect of a cognitive behavioral intervention on reducing symptom severity during chemotherapy. J Clin Oncol 2004;22:507-16.  Back to cited text no. 41
    
42.Goedendorp MM, Gielissen MF, Verhagen CA, Bleijenberg G. Psychosocial interventions for reducing fatigue during cancer treatment in adults. Cochrane Database Syst Rev 2009;21: CD006953.  Back to cited text no. 42
    
43.Boesen EH, Ross L, Frederiksen K, Thomsen BL, Dahlstrøm K, Schmidt G, et al. Psychoeducational intervention for patients with cutaneous malignant melanoma: A replication study. J Clin Oncol 2005;23:1270-7.  Back to cited text no. 43
    
44.Jacobsen PB, Meade CD, Stein KD, Chirikos TN, Small BJ, Ruckdeschel JC. Efficacy and costs of two forms of stress management training for cancer patients undergoing chemotherapy. J Clin Oncol 2002;20:2851-62.  Back to cited text no. 44
    
45.Gielissen MF, Verhagen S, Witjes F, Bleijenberg G. Effects of cognitive behaviour therapy in severely fatigued disease-free cancer patients compared with patients waiting for cognitive behavior therapy: a randomized controlled trial. J Clin Oncol 2006;24:4882-7.  Back to cited text no. 45
    
46.Gaston-Johansson F, Fall-Dickson JM, Nanda J, Ohly KV, Stillman S, Krumm S, et al. The effectiveness of the comprehensive coping strategy program on clinical outcomes in breast cancer autologous bone marrow transplantation. Cancer Nurs 2000;23:277-85.  Back to cited text no. 46
    
47.Bruera E, Valero V, Driver L, Shen L, Willey J, Zhang T, et al. Patient-controlled methylphenidate for cancer fatigue: A double-blind, randomized, placebo-controlled trial. J Clin Oncol 2006;24:2073-8.  Back to cited text no. 47
    
48.Sarhill N, Walsh D, Nelson KA, Homsi J, LeGrand S, Davis MP. Methylphenidate for fatigue in advanced cancer: A prospective open-label pilot study. Am J Hosp Palliat Care 2001;18:187-92.  Back to cited text no. 48
    
49.Blackhall L, Petroni G, Shu J, Baum L, Farace E. A pilot study evaluating the safety and efficacy of modafinal for cancer-related fatigue. J Palliat Med 2009;12:433-9.  Back to cited text no. 49
    
50.Jean-Pierre P, Morrow GR, Roscoe JA, Heckler C, Mohile S, Janelsins M, et al. A phase 3 randomized, placebocontrolled, double-blind, clinical trial of the effect of modafinil on cancer-related fatigue among 631 patients receiving chemotherapy: A University of Rochester Cancer Center Community Clinical Oncology Program Research base study. Cancer 2010;116:3513-20.  Back to cited text no. 50
    
51.Auret KA, Schug SA, Bremner AP, Bulsara M. A randomized, double-blind, placebo-controlled trial assessing the impact of dexamphetamine on fatigue in patients with advanced cancer. J Pain Symptom Manage 2009;37:613-21.  Back to cited text no. 51
    
52.de Souza Fêde AB, Bensi CG, Trufelli DC, de Oliveira Campos MP, Pecoroni PG, Ranzatti RP, et al. Multivitamins do not improve radiation therapy-related fatigue: Results of a double-blind randomized crossover trial. Am J Clin Oncol 2007;30:432-6.  Back to cited text no. 52
    
53.Stockler MR, O'Connell R, Nowak AK, Goldstein D, Turner J, Wilcken NR, et al. Effect of sertraline on symptoms and survival in patients with advanced cancer, but without major depression: A placebo-controlled double-blind randomised trial. Lancet Oncol 2007;8:603-12.  Back to cited text no. 53
    
54.Minton O, Richardson A, Sharpe M, Hotopf M, Stone P. A systematic review and metaanalysis of the pharmacological treatment of cancer-related fatigue. J Natl Cancer Inst 2008;100:1155-66.  Back to cited text no. 54
    
55.Minton O, Richardson A, Sharpe M, Hotopf M, Stone P. Drug therapy for the management of cancer-related fatigue. Cochrane Database Syst Rev 2010;7:CD006704.  Back to cited text no. 55
    
56.Vickers AJ, Straus DJ, Fearon B, Cassileth BR. Acupuncture for postchemotherapy fatigue: A phase II study. J Clin Oncol 2004;22:1731-5.  Back to cited text no. 56
    
57.Barsevick AM, Dudley W, Beck S, Sweeney C, Whitmer K, Nail L. A randomized clinical trial of energy conservation for patients with cancer-related fatigue. Cancer 2004;100:1302-10.  Back to cited text no. 57
    
58.Post-White J, Kinney ME, Savik K, Gau JB, Wilcox C, Lerner I. Therapeutic massage and healing touch improve symptoms in cancer. Integr Cancer Ther 2003;2:332-44.  Back to cited text no. 58
    
59.Bakke AC, Purtzer MZ, Newton P. The effect of hypnoticguided imagery on psychological well-being and immune function in patients with prior breast cancer. J Psychosom Res 2002;53:1131-7.  Back to cited text no. 59
    
60.Schumacher K, Schneider B, Reich G, Stiefel T, Stoll G, Bock PR, et al. Influence of postoperative complementary treatment with lectin-standardized mistletoe extract on breast cancer patients: A controlled epidemiological multicentric retrolective cohort study. Anticancer Res 2003;23:5081-7.  Back to cited text no. 60
    
61.Graziano F, Bisonni R, Catalano V, Silva R, Rovidati S, Mencarini E, et al. Potential role of levocarnitine supplementation for the treatment of chemotherapy- induced fatigue in non-anaemic cancer patients. Br J Cancer 2002;86:1854-7.  Back to cited text no. 61
    
62.Ahles TA, Tope DM, Pinkson B, Walch S, Hann D, Whedon M, et al. Massage therapy for patients undergoing autologous bone marrow transplantation. J Pain Symptom Manage 1999;18:157-63.  Back to cited text no. 62
    
63.Berger A. Treating fatigue in cancer patients. Oncologist 2003;8:10-4.  Back to cited text no. 63
    
64.Cohen L, Warneke C, Fouladi RT, Rodriguez MA, Chaoul-Reich A. Psychological adjustment and sleep quality in a randomized trial of the effects of a Tibetan yoga intervention in patients with lymphoma. Cancer 2004;100:2253-60.  Back to cited text no. 64
    



 
 
    Tables

  [Table 1], [Table 2]



 

Top
Print this article  Email this article
Online since 1st October '05
Published by Medknow