Exercise Therapy and Fatigue Management

  • Jack B. Fu
  • Arash Asher


Cancer-related fatigue is a common and troubling symptom for cancer patients. Its physiologic mechanisms are complex and interplay with other symptoms, hormonal changes, deconditioning, and a pro-inflammatory state. While further studies are needed, current evidence suggests exercise results in reduced cancer-related fatigue compared to other existing treatments. A combination of resistive and aerobic exercises reduces fatigue. Unfortunately, the wide variation in exercise programs studied means that the most effective types of exercise and optimal doses of exercise are unclear. Despite a growing amount of evidence to support the beneficial effects of exercise on fatigue and other cancer symptoms; it is under-addressed by cancer healthcare professionals.


Exercise Fatigue Cancer Inflammation Physiatry Rehabilitation 



Cancer-related fatigue


Energy conservation and activity management


Functional Assessment of Cancer Therapy: Fatigue


  1. 1.
    Servaes P, Verhagen C, Bleijenberg G. Fatigue in cancer patients during and after treatment: prevalence, correlates and interventions. Eur J Cancer. 2002;38:27–43.PubMedCrossRefGoogle Scholar
  2. 2.
    Butt Z, Rosenbloom SK, Abernethy AP, Beaumont JL, Paul D, Hampton D, Jacobsen PB, Syrjala KL, Von Roenn JH, Cella D. Fatigue is the most important symptom for advanced cancer patients who have had chemotherapy. J Natl Compr Cancer Netw. 2008;6(5):448–55.CrossRefGoogle Scholar
  3. 3.
    Chanudrhuri A, Behan PO. Fatigue and basal ganglia. J Neurol Sci. 2000;179:34–42.CrossRefGoogle Scholar
  4. 4.
    Cancer-related fatigue (version 1.2010). National Comprehensive Cancer Network; 2010. Accessed 2 Jan 2010.
  5. 5.
    Cella D, Lai JS, Chang CH, Peterman A, Slavin M. Fatigue in cancer patients compared with fatigue in the general Untied States population. Cancer. 2002;94:528–38.PubMedCrossRefGoogle Scholar
  6. 6.
    Chaudhuri A, Behan PO. Fatigue in neurological disorders. Lancet. 2004;363:978–88.PubMedCrossRefGoogle Scholar
  7. 7.
    Mitchell SA. Cancer-related fatigue: state of the science. PM R. 2010;2(5):364–83.PubMedCrossRefGoogle Scholar
  8. 8.
    Curt GA. The impact of fatigue on patients with cancer. Overview of fatigue 1 and 2. Oncologist. 2000;5:9–12.PubMedCrossRefGoogle Scholar
  9. 9.
    Vogelzang NJ, Breitbart W, Cella D, Curt GA, Groopman JE, Horning SJ, Itri LM, Johnson DH, Scherr SL, Portenoy RK. Patient, caregiver, and oncologist perceptions of cancer-related fatigue: results of a tripart assessment survey. The fatigue coalition. Semin Hematol. 1997;34(3 Suppl 2):4–12.PubMedGoogle Scholar
  10. 10.
    Knowles G, Borthwick D, McNamara S, Miller M, Leggot L. Survey of nurses’ assessment of cancer-related fatigue. Eur J Cancer Care (Engl). 2000;9(2):105–13.CrossRefGoogle Scholar
  11. 11.
    Shun SC, Lai YH, Hsiao FH. Patient-related barriers to fatigue communication in cancer patients receiving active treatment. Oncologist. 2009;14(9):936–43.PubMedCrossRefGoogle Scholar
  12. 12.
    Collins S, de Vogel-Voogt E, Visser A, van der Heide A. Presence, communication and treatment of fatigue and pain complaints in incurable cancer patients. Patient Educ Couns. 2008;72(1):102–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Mendoza TR, Wang XS, Cleeland CS, et al. The rapid assessment of fatigue severity in cancer patients: use of the brief fatigue inventory. Cancer. 1999;85:1186–96.PubMedCrossRefGoogle Scholar
  14. 14.
    Yellen SB, Cella DF, Webster K, Blendowski C, Kaplan E. Measuring fatigue and other anemia-related symptoms with the Functional Assessment of Cancer therapy (FACT) measurement system. J Pain Symptom Manag. 1997;13(2):63–74.CrossRefGoogle Scholar
  15. 15.
    Piper BF, Dibble SL, Dodd MJ, Weiss MC, Slaughter RE, Paul SM. The revised Piper fatigue scale: psychometric evaluation in women with breast cancer. Oncol Nurs Forum. 1998;25:677–84.PubMedGoogle Scholar
  16. 16.
    Smets EM, Garssen B, Bonke B, De Haes JC. The Multidimensional Fatigue Inventory (MFI) psychometric qualitifes of an instrument to assess fatigue. J Psychosom Res. 1995;39:315–25.PubMedCrossRefGoogle Scholar
  17. 17.
    Paddison JS, Temel JS, Fricchione GL, Pirl WF. Using the differential from complete blood counts as a biomarker of fatigue in advanced non-small cell lung cancer: an exploratory analysis. Palliat Support Care. 2009;7:213–7.PubMedCrossRefGoogle Scholar
  18. 18.
    Capuano G, Gentile PC, Bianciardi F, Tosti M, Palladino A, Di Palma M. Prevalence and influence of malnutrition on quality of life and performance status in patients with locally advanced head and neck cancer before treatment. Support Care Cancer. 2009;18:433–7.PubMedCrossRefGoogle Scholar
  19. 19.
    Ray M, Rogers LQ, Trammell RA, Toth LA. Fatigue and sleep during cancer and chemotherapy: translation rodent models. Comp Med. 2008;58:234–45.PubMedPubMedCentralGoogle Scholar
  20. 20.
    Sateia MJ, Lang BJ. Sleep and cancer: recent developments. Curr Oncol Rep. 2008;10:309–18. Francoeur RB. The relationship of cancer symptom clusters to depressive affect in the initial phase of palliative radiation. J Pain Symptom Manag. 2005;29:130–55.Google Scholar
  21. 21.
    Ancoli-Israel S, Liu L, Marler MR, et al. Fatigue, sleep, and circadian rhythms prior to chemotherapy for breast cancer. Support Care Cancer. 2006;14:201–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Strasser F, Palmer JL, Schover LR, et al. The impact of hypogonadism and autonomic dysfunction on fatigue, emotional functional and sexual desire in male patients with advanced cancer: a pilot study. Cancer. 2006;107:2949–57.PubMedCrossRefGoogle Scholar
  23. 23.
    Bower JE, Ganz PA, Dickerson SS, Peterson L, Aziz N, Fahey JL. Diurnal cortisol rhythm and fatigue in breast cancer survivors. Psychoneuroendocrinology. 2005;30:92–100.PubMedCrossRefGoogle Scholar
  24. 24.
    al-Majid S, McCarthy DO. Cancer-related fatigue and skeletal muscle wasting: the role of exercise. Biol Res Nurs. 2001;2:186–97.PubMedCrossRefGoogle Scholar
  25. 25.
    Yavuzsen T, Davis MP, Ranganathan VK, et al. Cancer-related fatigue: central or peripheral? J Pain Symptom Manag. 2009;38:587–96.CrossRefGoogle Scholar
  26. 26.
    Bower JE. Cancer-related fatigue: links with inflammation in cancer patients and survivors. Brain Behav Immun. 2007;21:863–71.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Collado-Hidalgo A, Bower JE, Ganz PA, Cole SW, Irwin MR. Inflammatory biomarkers for persistent fatigue in breast cancer survivors. Clin Cancer Res. 2006;12:2759–66.PubMedCrossRefGoogle Scholar
  28. 28.
    Schubert C, Hong S, Natarajan L, Mills PJ, Dimsdale JE. The association between fatigue and inflammatory marker levels in cancer patients: a quantitative review. Brain Behav Immun. 2007;21:413–27.PubMedCrossRefGoogle Scholar
  29. 29.
    Wood LJ, Nail LM, Gilster A, Winters KA, Elsea CR. Cancer chemotherapy-related symptoms: evidence to suggest a role for proinflammatory cytokines. Oncol Nurs Forum. 2006;33:535–42.PubMedCrossRefGoogle Scholar
  30. 30.
    Jager A, Sleifer S, van der Rijt CC. The pathogenesis of cancer related fatigue: could increased activity of pro-inflammatory cytokines be the common denominator? Eur J Cancer. 2008;44:175–81.PubMedCrossRefGoogle Scholar
  31. 31.
    Seruga B, Zhang H, Bernstein LJ, Tannock IF. Cytokines and their relationship to the symptoms and outcome of cancer. Nat Rev Cancer. 2008;8(11):887–99.PubMedCrossRefGoogle Scholar
  32. 32.
    Strong V, Waters R, Hibberd C, et al. Management of depression for people with cancer (SMaRT oncology 1): a randomized trial. Lancet. 2008;372:40–8.PubMedCrossRefGoogle Scholar
  33. 33.
    Savard J, Simard S, Giguere I, et al. Randomized clinical trial on cognitive therapy for depression in women with metastatic breast cancer: psychological and immunological effects. Palliat Support Care. 2006;4:219–37.PubMedCrossRefGoogle Scholar
  34. 34.
    Levesque M, Savard J, Simard S, Guathier JG, Ivers H. Efficacy of cognitive therapy for depression among women with metastatic cancer: a single-case experimental study. J Behav Ther Exp Psychiatry. 2004;35:287–305.PubMedCrossRefGoogle Scholar
  35. 35.
    Hrushesky WJ, Grutsch JF, Wood P, et al. Circadian clock manipulation for cancer prevention and control and the relief of cancer symptoms. Integr Cancer Ther. 2009;8:387–97.PubMedCrossRefGoogle Scholar
  36. 36.
    Minton O, Richardson A, Sharpe M, Hotopf M, Stone PC. Psychostimulants for the management of cancer-related fatigue: a systematic review and meta-analysis. J Pain Symptom Manag. 2011;41(4):761–7.CrossRefGoogle Scholar
  37. 37.
    Mantovani G, Macciò A, Madeddu C, Serpe R, Antoni G, Massa E, Dessì M, Panzone F. Phase II nonrandomized study of the efficacy and safety of COX-2 inhibitor celecoxib on patients with cancer cachexia. J Mol Med (Berl). 2010;88(1):85–92.CrossRefGoogle Scholar
  38. 38.
    Monk JP, Phillips G, Waite R, Kuhn J, Schaaf LJ, Otterson GA, Guttridge D, Rhoades C, Shah M, Criswell T, Caligiuri MA, Villalona-Calero MA. Assessment of tumor necrosis factor alpha blockade as an intervention to improve tolerability of dose-intensive chemotherapy in cancer patients. J Clin Oncol. 2006;24(12):1852–9.PubMedCrossRefGoogle Scholar
  39. 39.
    Minton O, Richardson A, Sharpe M, Hotopf M, Stone P. A systematic review and meta-analysis of the pharmacological treatment of cancer-related fatigue. J Natl Cancer Inst. 2008;100(16):1155–66.PubMedCrossRefGoogle Scholar
  40. 40.
    Jones M, Schenkel B, Just J, Fallowfield L. Epoetin alfa improves quality of life in patients with cancer: results of meta-analysis. Cancer. 2004;101:1720–32.PubMedCrossRefGoogle Scholar
  41. 41.
    Cella D, Dobrez D, Glaspy J. Control of cancer-related anemia with erythropoietic agents: a review of evidence for improved quality of life and clinical outcomes. Ann Oncol. 2003;14:511–9.PubMedCrossRefGoogle Scholar
  42. 42.
    Littlewood TJ, Cella D, Nortier JW. Erythropoietin improves quality of life. Lancet Oncol. 2002;3:459–60.PubMedCrossRefGoogle Scholar
  43. 43.
    Schmitz KH, Courneya KS, Matthews C, Demark-Wahnefried W, Galvão DA, Pinto BM, Irwin ML, Wolin KY, Segal RJ, Lucia A, Schneider CM, von Gruenigen VE, Schwartz AL, American College of Sports Medicine. American College of Sports Medicine roundtable on exercise guidelines for cancer survivors. Med Sci Sports Exerc. 2010;42(7):1409–26.PubMedCrossRefGoogle Scholar
  44. 44.
    Speed-Andrews AE, Courneya KS. Effects of exercise on quality of life and prognosis in cancer survivors. Curr Sports Med Rep. 2009;8:176–81.PubMedCrossRefGoogle Scholar
  45. 45.
    van Weert E, Hoekstra-Weebers J, Otter R, Postema K, Sanderman R, van der Schans C. Cancer-related fatigue: predictors and effects of rehabilitation. Oncologist. 2006;11:184–96.PubMedCrossRefGoogle Scholar
  46. 46.
    Segal R, Evans W, Johnson D, et al. Structured exercise improves physical functioning in women with stages I and II breast cancer: results of a randomized controlled trial. J Clin Oncol. 2001;19(3):657–65.PubMedCrossRefGoogle Scholar
  47. 47.
    Milne HM, Wallman KE, Gordon S, et al. Effects of a combined aerobic and resistance exercise program in breast cancer survivors: a randomized controlled trial. Breast Cancer Res Treat. 2008;108(2):279–88.PubMedCrossRefGoogle Scholar
  48. 48.
    Courneya KS, Friedenreich CM, Sela RA, et al. The group psychotherapy and home-based physical exercise (group-hope) trial in cancer survivors: physical fitness and quality of life outcomes. Psychooncology. 2003;12(4):357–74.PubMedCrossRefGoogle Scholar
  49. 49.
    Klika RJ, Callahan KE, Drum SN. Individualized 12-week exercise training programs enhance aerobic capacity of cancer survivors. Phys Sportsmed. 2009;39:68–77.CrossRefGoogle Scholar
  50. 50.
    McAuley E, White SM, Rogers LQ, Motl RW, Courneya KS. Physical activity and fatigue in breast cancer and multiple sclerosis: psychosocial mechanisms. Psychosom Med. 2010;72:88–96.PubMedCrossRefGoogle Scholar
  51. 51.
    Basen-Engquist K, Scruggs S, Jhingran A, et al. Physical activity and obesity in endometrial cancer survivors: associations with pain, fatigue, and physical functioning. Am J Obstet Gynecol. 2009;200:288 e281–8.CrossRefGoogle Scholar
  52. 52.
    Item F, Konrad D. Visceral fat and metabolic inflammation: the portal theory revisited. Obes Rev. 2012;13 Suppl 2:30–9.PubMedCrossRefGoogle Scholar
  53. 53.
    Bruunsgaard H. Physical activity and modulation of systemic low-level inflammation. J Leukoc Biol. 2005;78:819–35.PubMedCrossRefGoogle Scholar
  54. 54.
    Ross R, Després JP. Abdominal obesity, insulin resistance, and the metabolic syndrome: contribution of physical activity/exercise. Obesity (Silver Spring). 2009;17(Suppl 3):S1–2.CrossRefGoogle Scholar
  55. 55.
    Pedersen BK, Fischer CP. Beneficial health effects of exercise—the role of IL-6 as a myokine. Trends Pharmacol Sci. 2007;28(4):152–6.PubMedCrossRefGoogle Scholar
  56. 56.
    Fischer CP. Interleukin-6 in acute exercise and training: what is the biological relevance? Exerc Immunol Rev. 2006;12:6–33.PubMedGoogle Scholar
  57. 57.
    Hill EE, Zack E, Battaglini C, Viru M, Viru A, Hackney AC. Exercise and circulating cortisol levels: the intensity threshold effect. J Endocrinol Investig. 2008;31(7):587–91.CrossRefGoogle Scholar
  58. 58.
    Warren JB, Dalton N, Turner C, Clark TJ, Toseland PA. Adrenaline secretion during exercise. Clin Sci (Lond). 1984;66(1):87–90.CrossRefGoogle Scholar
  59. 59.
    Petersen AM, Pedersen BK. The anti-inflammatory effect of exercise. J Appl Physiol (1985). 2005;98(4):1154–62.CrossRefGoogle Scholar
  60. 60.
    Surmi BK, Hasty AH. Macrophage infiltration into adipose tissue: initiation, propagation and remodeling. Future Lipidol. 2008;3(5):545–56.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Gleeson M, McFarlin B, Flynn M. Exercise and toll-like receptors. Exerc Immunol Rev. 2006;12:34–53.PubMedGoogle Scholar
  62. 62.
    Kruijsen-Jaarsma M, Révész D, Bierings MB, Buffart LM, Takken T. Effects of exercise on immune function in patients with cancer: a systematic review. Exerc Immunol Rev. 2013;19:120–43.PubMedGoogle Scholar
  63. 63.
    Jones SB, Thomas GA, Hesselsweet SD, Alvarez-Reeves M, Yu H, Irwin ML. Effect of exercise on markers of inflammation in breast cancer survivors: the Yale exercise and survivorship study. Cancer Prev Res (Phila). 2013;6(2):109–18.CrossRefGoogle Scholar
  64. 64.
    Fu JB, Raj VS, Guo Y. A Guide to Inpatient Cancer Rehabilitation: Focusing on Patient Selection and Evidence-Based Outcomes. PM R. 2017;9(9S2):S324–S334.CrossRefGoogle Scholar
  65. 65.
    Sabatino SA, Coates RJ, Uhler RJ, Pollack LA, Alley LG, Zauderer LJ. Provider counseling about health behaviors among cancer survivors in the United States. J Clin Oncol. 2007;25(15):2100–6.PubMedCrossRefGoogle Scholar
  66. 66.
    Brown P, Clark MM, Atherton P, et al. Will improvements in quality of life (QOL) impact fatigue in patients receiving radiation therapy for advanced cancer? Am J Clin Oncol. 2006;29:52–8.PubMedCrossRefGoogle Scholar
  67. 67.
    Nieman DC. Exercise, infection, and immunity. Int J Sports Med. 1994;15(Suppl 3):S131–41.PubMedCrossRefGoogle Scholar
  68. 68.
    Courneya KS, Segal RJ, Mackey JR, et al. Effects of aerobic and resistance exercise in breast cancer patients receiving adjuvant chemotherapy: a multicenter randomized controlled trial. J Clin Oncol. 2007;25:4396–404.PubMedCrossRefGoogle Scholar
  69. 69.
    Cristian A, Tran A, Patel K. Patient safety in cancer rehabilitation. Phys Med Rehabil Clin N Am. 2012;23(2):441–56. Epub 2012 Apr 10.PubMedCrossRefGoogle Scholar
  70. 70.
    van Weert E, Hoekstra-Weebers JE, May AM, Korstjens I, Ros WJ, van der Schans CP. The development of an evidence-based physical self-management rehabilitation programme for cancer survivors. Patient Educ Couns. 2008;71:169–90.PubMedCrossRefGoogle Scholar
  71. 71.
    Jacobsen PB, Donovan KA, Vandaparmpil ST, Small BJ. Systematic review and meta-analysis of psychological and activity-based interventions for cancer-related fatigue. Health Psychol. 2007;26(6):660–7.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Barsevick AM, Whitmer K, Sweeney C, Nail LM. A pilot study examining energy conservation for cancer treatment-related fatigue. Cancer Nurs. 2002;25:333–41.PubMedCrossRefGoogle Scholar
  73. 73.
    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.PubMedCrossRefGoogle Scholar
  74. 74.
    Danhauer SC, Tooze JA, Farmer DF, et al. Restorative yoga for women with ovarian or breast cancer: findings from a pilot study. J Soc Integr Oncol. 2008;6:47–58.PubMedGoogle Scholar
  75. 75.
    Bower JE, Greendale G, Crosswell AD, Garet D, Sternlieb B, Ganz PA, Irwin MR, Olmstead R, Arevalo J, Cole SW. Yoga reduces inflammatory signaling in fatigued breast cancer survivors: a randomized controlled trial. Psychoneuroendocrinology. 2014;43:20–9.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Zeng Y, Luo T, Finnegan-John J, Cheng AS. Meta-analysis of randomized controlled trials of acupuncture for cancer-related fatigue. Integr Cancer Ther. 2013;13:193–200.PubMedCrossRefGoogle Scholar
  77. 77.
    Cohen M, Fried G. Comparing relaxation training and cognitive-behavioral group therapy for women with breast cancer. Res Soc Work Pract. 2007;17:313–23.CrossRefGoogle Scholar
  78. 78.
    Danhauer SC, Tooze JA, Holder P, Miller C, Jesse MT. Healing touch as a supportive intervention for adult acute leukemia patients: a pilot investigation of effects on distress and symptoms. J Soc Integr Oncol. 2008;6:89–97.PubMedPubMedCentralGoogle Scholar
  79. 79.
    Dietz JH. Rehabilitation of the cancer patient: its role in the scheme of comprehensive care. Clin Bull. 1974;4(3):104–7.PubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Palliative, Rehabilitation and Integrative MedicineUniversity of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical CenterLos AngelesUSA

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