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Management of fatigue in cancer patients

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Abstract

Cancer-related fatigue (CRF) is either a symptom or a syndrome depending on criteria for diagnosis. CRF is present in 20% to 30% of long-term cancer survivors and 80% to 90% during treatment and at the end of life. Assessment requires determining the presence, severity, and interference with daily activities. Different descriptors for fatigue (eg, tiredness, lack of vigor) measure different patient experiences. Associated factors such as depression, pain, insomnia, dyspnea, anemia, and deconditioning worsen CRF and should be treated if present. Associated factors that contribute to the severity of fatigue differ depending on the stage of cancer. Pharmacologic interventions include recombinant erythropoietin, psychostimulants, corticosteroid, antiin flammatory drugs other than steroids, and L-carnitine. Advances in the management of CRF will require an understanding of the underlying mechanism before targetspeci fic therapies can be developed.

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References and Recommended Reading

  1. Mock V: Evidence-based treatment for cancer-related fatigue. J Natl Cancer Inst Monogr 2004, 32:112–118. All who even have a passing interest in CRF should read this review of the evidence base for treating fatigue. Victoria Mock has packed an enormous amount of information in six pages.

    Article  PubMed  Google Scholar 

  2. Meek PM, Nail LM, Baresevick A, et al.: Psychometric testing of fatigue instruments for use with cancer patients. Nurs Res 2000, 49:181–190.

    Article  PubMed  CAS  Google Scholar 

  3. Mock V, Atkinson A, Barsevick A, et al.: NCCN Practice Guidelines for Cancer-related fatigue. Oncology (Williston Park) 2000, 12:151–161. These guidelines are helpful when managing CRF.

    Google Scholar 

  4. Manzullo EF, Escalante CP: Research into fatigue. Hematol Oncol Clin North Am 2002, 16:619–628.

    Article  PubMed  Google Scholar 

  5. Schwartz AL, Nail LM, Chen S, et al.: Fatigue patterns observed in patients receiving chemotherapy and radiotherapy. Cancer Invest 2000, 18:11–19.

    PubMed  CAS  Google Scholar 

  6. al-Majid S, McCarthy DO: Cancer-induced fatigue and skeletal muscle wasting: the role of exercise. Biol Res Nurs 2001, 2:186–197.

    Article  PubMed  CAS  Google Scholar 

  7. Smets EM, Garssen B, Cull A, et al.: Application of the multidimensional fatigue inventory (MFI-20) in cancer patients receiving radiotherapy. Br J Caner 1996, 73:241–245.

    CAS  Google Scholar 

  8. Holley S: Cancer-related fatigue: suffering a different fatigue. Cancer Pract 2000, 8:87–95.

    Article  PubMed  CAS  Google Scholar 

  9. Davidson JR, MacLean AW, Brundage MD, et al.: Sleep disturbance in cancer patients. Soc Sci Med 2002, 54:1309–1321.

    Article  PubMed  Google Scholar 

  10. Ahlberg K, Ekman T, Gaston-Johansson F, Mock V: Assessment and management of cancer-related in fatigue in adults. Lancet 2003, 362:640–650. An excellent review that also includes an algorithm for managing CRF based on NCCN guidelines

    Article  PubMed  Google Scholar 

  11. Dimeo F, Stieglitz RD, Novelli-Fischer U: Correlation between physical performance and fatigue in cancer patients. Ann Oncol 1997, 8:1251.

    Article  PubMed  CAS  Google Scholar 

  12. Stone P, Richardson A, Ream E, et al.: Cancer-related fatigue: inevitable, unimportant, and untreatable? Results of a multicentre patient survey. Cancer Fatigue Forum. Ann Oncol 2000, 11:971–975. One of the largest cross-sectional studies on the prevalence and characteristics of CRF.

    Article  PubMed  CAS  Google Scholar 

  13. Servaes P, van der Werf S, Prins J, et al.: Fatigue in disease-free cancer patients compared with fatigue in patients with chronic fatigue syndrome. Support Care Cancer 2001, 9:11–17.

    Article  PubMed  CAS  Google Scholar 

  14. Servaes P, Verhagen S, Bleijenberg G: Detriments of chronic fatigue in disease-free breast cancer patients: a cross-sectional study. Ann Oncol 2002, 13:589–598.

    Article  PubMed  CAS  Google Scholar 

  15. Servaes P, Verhagen S, Schreuder HW, et al.: Fatigue after treatment for malignant and benign bone and soft tissue tumors. J Pain Symptom Manage 2003, 26:1113–1122.

    Article  PubMed  Google Scholar 

  16. Bruera E, Ernst S, Hagen N, et al.: Effectiveness of megestrol acetate in patients with advanced cancer: a randomized, double-blind, crossover study. Cancer Prev Control 1998, 2:74–78.

    PubMed  CAS  Google Scholar 

  17. Bower JE, Ganz PA, Desmond KA, et al.: Fatigue in long-term breast carcinoma survivors: a longitudinal investigation. Cancer 2006, 106:751–758.

    Article  PubMed  Google Scholar 

  18. Young KE, White CA: The prevalence and moderators of fatigue in people who have been successfully treated for cancer. J Psychosom Res 2006, 60:29–38.

    Article  PubMed  Google Scholar 

  19. Lawrence DP, Kupelnick B, Miller K, et al.: Evidence report on the occurrence, assessment, and treatment of fatigue in cancer patients. J Natl Cancer Inst Monogr 2004, 32:40–50. I particularly like this review. It is well written and provides an accurate assessment of the evidence for treatment.

    Article  PubMed  Google Scholar 

  20. de Jong N, Candel MJ, Schouten HC, et al.: Prevalence and course of fatigue in breast cancer patients receiving adjuvant chemotherapy. Ann Oncol 2004, 15:896–905.

    Article  PubMed  Google Scholar 

  21. Haghighat S, Akbari ME, Holakouei K, et al.: Factors predicting fatigue in breast cancer patients. Support Care Cancer 2003, 11:533–538.

    Article  PubMed  Google Scholar 

  22. Rich T, Innominato PF, Boerner J, et al.: Elevated serum cytokines correlated with altered behavior, serum cortisol rhythm, and dampened 24-hour rest-activity patterns in patients with metastatic colorectal cancer. Clin Cancer Res 2005, 11:1757–1764.

    Article  PubMed  CAS  Google Scholar 

  23. van Andel G, Kurth KH: The impact of androgen deprivation therapy on health-related quality of life in asymptomatic men with lymph node positive prostate cancer. Eur Urol 2003, 44:209–214.

    Article  PubMed  Google Scholar 

  24. Howell SJ, Radford JA, Smets EM, et al.: Fatigue, sexual function, and mood following treatment for hematological malignancy: the impact of mild Ledig cell dysfunction. Br J Cancer 2000, 82:789–793.

    Article  PubMed  CAS  Google Scholar 

  25. Holzner B, Kemmler G, Greil R, et al.: The impact of hemoglobin levels on fatigue and quality of life in cancer patients. Ann Oncol 2002, 13:965–973.

    Article  PubMed  CAS  Google Scholar 

  26. Elenkov IJ, Iezzoni DG, Daly A, et al.: Cytokine deregulation, inflammation, and well-being. Neuroimmunomodulation 2005, 12:255–269.

    Article  PubMed  CAS  Google Scholar 

  27. Hickok JT, Morrow GR, Roscoe JA, et al.: Occurrence, severity, and longitudinal course of twelve common symptoms in 1129 consecutive patients during radiotherapy for cancer. J Pain Symptom Manage 2005, 30:433–442.

    Article  PubMed  Google Scholar 

  28. Visser MR, Smets EM: Fatigue, depression, and quality of life in cancer patients: How are they related? Support Care Cancer 1998, 6:101–108.

    Article  PubMed  CAS  Google Scholar 

  29. Monga U, Jaweed M, Kerrigan AJ, et al.: Neuromuscular fatigue in prostate cancer patients undergoing radiation therapy. Arch Phys Med Rehab 1997, 78:961–966.

    Article  CAS  Google Scholar 

  30. Morrow GR, Andrews PL, Hickok JT, et al.: Fatigue associated with cancer and its treatment. Support Care Cancer 2002, 10:389–398. This article contains a unique discussion on the hypotheses regarding specific mechanisms that may cause CRF.

    Article  PubMed  Google Scholar 

  31. Given B, Given CW, McCorkle R, et al.: Pain and fatigue management: results of a nursing randomized clinical trial. Oncol Nurs Forum 2002, 29:949–956.

    PubMed  Google Scholar 

  32. Munch TN, Zhang T, Willey J, et al.: The association between anemia and fatigue in patients with advanced cancer receiving palliative care. J Palliat Med 2005, 8:1144–1149. These investigators demonstrate that fatigue in advanced cancer is not associated with anemia. We should re-think transfusions and erythropoietin for fatigue in the palliative population.

    Article  PubMed  Google Scholar 

  33. Stone P, Richards M, A’Hern R, et al.: A study to investigate the prevalence, severity, and correlates of fatigue among patients with cancer in comparison with a control group of volunteers without cancer. Ann Oncol 2000, 11:561–567.

    Article  PubMed  CAS  Google Scholar 

  34. Bruera E, Sala R, Rico MA, et al.: Effects of parenteral hydration in terminally ill cancer patients: a preliminary study. J Clin Oncol 2005, 23:2366–2371.

    Article  PubMed  Google Scholar 

  35. Brown DJ, McMillan DC, Milroy R: The correlation between fatigue, physical function, the systemic inflammatory response, and psychological distress in patients with advanced lung cancer. Cancer 2005, 103:377–382.

    Article  PubMed  Google Scholar 

  36. Stone P, Hardy J, Broadley K, et al.: Fatigue in advanced cancer: a prospective, controlled, cross-sectional study. Br J Cancer 1999, 79:1479–1486.

    Article  PubMed  CAS  Google Scholar 

  37. Sadler I, Jacobsen P, Booth-Jones M, et al.: Preliminary evaluation of a clinical syndrome approach to assessing cancer-related fatigue. J Pain Symptom Manage 2002, 23:406–416.

    Article  PubMed  Google Scholar 

  38. Bruera E, Brennies C, Michaud M, et al.: Muscle electrophysiology in patients with advanced breast cancer. J Natl Cancer Inst 1988, 80:282–285.

    Article  PubMed  CAS  Google Scholar 

  39. Moertel CG, Schutt AJ, Reitemeier RJ, et al.: Corticosteroid therapy of preterminal gastrointestinal cancer. Cancer 1974, 33:1607–1609.

    Article  PubMed  CAS  Google Scholar 

  40. Bruera E, Roca E, Cedaro L, et al.: Action of oral methylprednisolone in terminal cancer patients: a prospective, randomized, double-blind study. Cancer Treat Rep 1985, 69:751–754.

    PubMed  CAS  Google Scholar 

  41. Ferrario E, Ferrari L, Bidoli P, et al.: Treatment of cancerrelated anemia with epoetin alfa: a review. Cancer Treat Rev 2004, 30:563–575. This review contains an excellent guideline for the use of erythropoietin to treat anemia and fatigue during chemotherapy.

    Article  PubMed  CAS  Google Scholar 

  42. Krishnasamy M: Fatigue in advanced cancer: meaning before measurement? Int J Nurs Stud 2000, 37:401–414. The individual meaning of fatigue in cancer cannot be measured by unidimensional scales, quality-of-life instruments, or validated multiple question assessment tools deigned for fatigue.

    Article  PubMed  CAS  Google Scholar 

  43. Knobel H, Loge JH, Brenne E, et al.: The validity of EORTC QLQ-C30 fatigue scale in advanced cancer patients and cancer survivors. Palliat Med 2003, 17:664–672.

    PubMed  Google Scholar 

  44. Sprangers MA, Van Dam FS, Broersen J, et al.: Revealing response shift in longitudinal research of fatigue: the use of the Then test approach. Acta Oncol 1999, 38:709–718. Just when we thought that measuring fatigue longitudinally was relatively simple!

    Article  PubMed  CAS  Google Scholar 

  45. Schwartz AL, Meek PM, Nail LM, et al.: Measurement of fatigue determining minimally important clinical differences. J Clin Epidemiol 2002, 55:239–244. Statistical differences and clinically perceived differences in fatigue are not the same.

    Article  PubMed  Google Scholar 

  46. Forester B, Kornfeld DS, Fleiss JL, et al.: Group psychotherapy during radiotherapy: effects on emotional and physical distress. Am J Psychiatry 1993, 150:1700–1706.

    PubMed  CAS  Google Scholar 

  47. Morrow GR, Hickok JT, Roscoe JA, et al.: Differential effects of paroxetine on fatigue and depression: a randomized, double-blind trial from the University of Rochester Cancer Center Community Clinical Oncology Program. J Clin Oncol 2003, 21:4635–4641.

    Article  PubMed  CAS  Google Scholar 

  48. Roscoe JA, Morrow GR, Hickok JT, et al.: Effect of paroxetine hydrochloride (Paxil) on fatigue and depression in breast cancer patients receiving chemotherapy. Breast Cancer Res Treat 2005, 89:243–249. So we now know that fatigue is not simply a form frusta of depression.

    Article  PubMed  CAS  Google Scholar 

  49. Manzullo E, Liu W, Escalante C: Treatment for cancerrelated fatigue: an update. Expert Rev Anticancer Ther 2003, 3:99–106.

    Article  PubMed  Google Scholar 

  50. Capuron L, Gumnick JF, Musselman DL, et al.: Neurobehavioral effects of interferon-alpha in cancer patients: phenomenology and paroxetine responsiveness of symptom dimensions. Neuropsychopharmacology 2002, 26:643–652.

    Article  PubMed  CAS  Google Scholar 

  51. Bower JE: Prevalence and causes of fatigue after cancer treatment: the next generation of research. J Clin Oncol 2005, 23:8280–8282.

    Article  PubMed  Google Scholar 

  52. Littlewood TJ, Bajetta E, Nortier JW, et al.: Effects of epoetin alfa on hematological parameters and quality of life in cancer patients receiving nonplatinum chemotherapy: results of a randomized, double-blind, placebo-controlled trial. J Clin Oncol 2001, 19:2865–2874.

    PubMed  CAS  Google Scholar 

  53. Cella D, Kallich J, McDermott A, et al.: The longitudinal relationship of hemoglobin, fatigue, and quality of life in anemic cancer patients: results from five randomized clinical trials. Ann Oncol 2004, 15:979–986. David Cella is a master at symptom instrument development. This is an excellent review for oncologists.

    Article  PubMed  CAS  Google Scholar 

  54. Vansteenkiste J, Pirker R, Massuti B, et al.: Double-blind, placebo-controlled, randomized, phase-III trial of darbepoetin alfa in lung cancer patients receiving chemotherapy. J Natl Cancer Inst 2002, 94:1211–1220.

    PubMed  CAS  Google Scholar 

  55. Cella D: The effects of anemia and anemia treatment on the quality of life of people with cancer. Oncology (Williston Park) 2002, 16(suppl 10):125–132.

    Google Scholar 

  56. Stricker CT, Drake D, Hoyer KA, et al.: Evidence-based practice for fatigue management in adults with cancer: exercise as an intervention. Oncol Nurs Forum 2004, 31:963–976.

    PubMed  Google Scholar 

  57. Dimeo FC: Effects of exercise on cancer-related fatigue. Cancer 2001, 92(suppl):1689–1693.

    Article  PubMed  CAS  Google Scholar 

  58. Schwartz AL, Mori M, Gao R, et al.: Exercise reduces daily fatigue in women with breast cancer receiving chemotherapy. Med Sci Sports Exerc 2001, 33:718–723.

    Article  PubMed  CAS  Google Scholar 

  59. Mock V, Frangakis C, Davidson NE, et al.: Exercise manages fatigue during breast cancer treatment: a randomized, controlled trial. Psychooncology 2005, 14:464–477.

    Article  PubMed  Google Scholar 

  60. Porock D, Kristjanson LJ, Tinnelly K, et al.: An exercise intervention for advanced cancer patients experiencing fatigue: a pilot study. J Palliat Care 2000, 16:30–36.

    PubMed  CAS  Google Scholar 

  61. Dimeo FC, Thomas F, Raabe-Menssen C, et al.: Effect of aerobic exercise and relaxation training on fatigue and physical performance of cancer patients after surgery: a randomized, controlled trial. Support Care Cancer 2004, 12:774–779.

    Article  PubMed  Google Scholar 

  62. Scott HR, McMillan DC, Forrest LM, et al.: The systemic inflammatory response, weight loss, performance status, and survival in patients with inoperable non-small cell lung cancer. Br J Cancer 2002, 87:264–267.

    Article  PubMed  CAS  Google Scholar 

  63. McMillan DC, Watson WS, O’Gorman P, et al.: Albumin concentrations are primarily determined by the body cell mass and the systemic inflammatory response in cancer patients with weight loss. Nutr Cancer 2001, 39:210–213.

    Article  PubMed  CAS  Google Scholar 

  64. Campbell AJ: Thyroid disorders in the elderly: difficulties in diagnosis and treatment. Drugs 1986, 31:455–461.

    PubMed  CAS  Google Scholar 

  65. Felicetta JV: Thyroid changes with aging: significance and management. Geriatrics 1987, 42:86–88, 91–92.

    PubMed  CAS  Google Scholar 

  66. Sarhill N, Walsh D, Nelson KA, et al.: Methylphenidate for fatigue in advanced cancer: a prospective, open-label pilot study. Am J Hosp Palliat Care 2001, 18:187–192.

    Article  PubMed  CAS  Google Scholar 

  67. Homsi J, Walsh D, Nelson KA: Psychostimulants in supportive care. Support Care Cancer 2000, 8:385–397.

    Article  PubMed  CAS  Google Scholar 

  68. Sugawara Y, Akechi T, Shima Y, et al.: Efficacy of methylphenidate for fatigue in advanced cancer patients: a preliminary study. Palliat Med 2002, 16:261–263.

    Article  PubMed  Google Scholar 

  69. Bruera E, Driver L, Valero V, et al.: Patient controlled methylphenidate (PCM for cancer-related fatigue (CRF): a randomized, controlled trial [Abstract]. J Clin Oncol 2005, 23(suppl):740s.

    Google Scholar 

  70. Morrow GR, Gillies LJ, Hickok JT, et al.: The positive effect of the psychostimulants modafinil on fatigue from cancer that persists after treatment is completed [Abstract]. J Clin Oncol 2005, 23(suppl):732s.

    Article  Google Scholar 

  71. Lower E, Fleishman S, Cooper A, et al.: A phase-III, randomized, placebo-controlled trial of the safety and efficacy of I-MPH as new treatment of fatigue and "Chemo brain" in adult cancer patients [Abstract]. J Clin Oncol 2005, 23(suppl):729s.

    Google Scholar 

  72. Williams JA, Shacter E. Regulation of macrophage cytokine production by prostaglandin E2: distinct roles of cyclooxygenase-1 and-2. J Biol Chem 1997, 272:25693–25699.

    Article  PubMed  CAS  Google Scholar 

  73. Mets T, Bautmans I, Njemini R, et al.: The influence of celecoxib on muscle fatigue resistance and mobility in elderly patients with inflammation. Am J Geriatr Pharmacother 2004, 2:230–238.

    Article  PubMed  CAS  Google Scholar 

  74. Bruera E, Moyano JR, Sala R, et al.: Dexamethasone in addition to metoclopramide for chronic nausea in patients with advanced cancer: a randomized, controlled trial. J Pain Symptom Manage 2004, 28:381–388.

    Article  PubMed  CAS  Google Scholar 

  75. Lee BN, Dantzer R, Langley KE, et al.: A cytokine-based neuroimmunologic mechanism of cancer-related symptoms. Neuroimmunomodulation 2004, 11:279–292.

    Article  PubMed  CAS  Google Scholar 

  76. Cerchietti LC, Navigante AH, Peluffo GD, et al.: Effects of celecoxib, medroxyprogesterone, and dietary intervention on systemic syndromes in patients with advanced lung Aden carcinoma: a pilot study. J Pain Symptom Manage 2004, 27:85–95.

    Article  PubMed  CAS  Google Scholar 

  77. Richelson E: Interactions of antidepressants with neurotransmitter transporters and receptors and their clinical relevance. J Clin Psychiatry 2003, 64(suppl 13):5–12.

    PubMed  CAS  Google Scholar 

  78. Cruciani RA, Dvorkin E, Homel P, et al.: L-carnitine supplementation for the treatment of fatigue and depressed mood in cancer patients with carnitine deficiency: a preliminary analysis. Ann N Y Acad Sci 2004, 1033:168–176.

    Article  PubMed  CAS  Google Scholar 

  79. Dodson WL, Sachan DS, Krauss S, et al.: Alterations of serum and urinary carnitine profiles in cancer patients: hypothesis of possible significance. J Am Coll Nutr 1989, 8:133–142.

    PubMed  CAS  Google Scholar 

  80. Anonymous: Monograph. L-carnitine. Altern Med Rev 2005, 10:42–50.

    Google Scholar 

  81. Kuratsune H, Yamaguti K, Lindh G, et al.: Brain regions involved in fatigue sensation: reduced acetylcarnitine uptake into the brain. Neuroimage 2002, 17:1256–1265.

    Article  PubMed  Google Scholar 

  82. Graziano F, Bisonni R, Catalano V, et al.: Potential role of levocarnitine supplementation for the treatment of chemotherapy-induced fatigue in non-anaemic cancer patients. Br J Cancer 2002, 86:1854–1857.

    Article  PubMed  CAS  Google Scholar 

  83. Sachan DS, Dodson WL: The serum carnitine status of cancer patients. J Am Coll Nutr 1987, 6:145–150.

    PubMed  CAS  Google Scholar 

  84. Mundy EA, DuHamel KN, Montgomery GH: The efficacy of behavioral interventions for cancer treatment-related side effects. Semin Clin Neuropsychiatry 2003, 8:253–275. An excellent synopsis of the value of nonpharmacologic approaches to symptom management during chemotherapy.

    PubMed  Google Scholar 

  85. Burish TG, Jenkins RA: Effectiveness of biofeedback and relaxation training in reducing the side effects of cancer chemotherapy. Health Psychol 1992, 11:17–23.

    Article  PubMed  CAS  Google Scholar 

  86. Doorenbos A, Given B, Given C: Reducing symptom limitations: a cognitive behavioral intervention randomized trial. Psychooncology 2005, 14:574–584.

    Article  PubMed  Google Scholar 

  87. Stegelis HE, Hagedoon M, Sanderman R, et al.: The impact of an informational self-management intervention on the association between control and illness uncertainty before and psychological distress after radiotherapy. Psychooncology 2004, 13:248–259.

    Article  Google Scholar 

  88. Rummans TA, Clark MM, Sloan JA, et al.: Impacting quality of life for patients with advanced cancer with a structured multidisciplinary intervention: a randomized, controlled trial. J Clin Oncol 2006, 24:635–642.

    Article  PubMed  Google Scholar 

  89. Gutstein HB: The biologic basis of fatigue. Cancer 2001, 92(suppl):1678–1683. Howard Gutstein hits at the heart of the matter when he says "Coincidence versus causation will be an issue until mechanisms of fatigue are better defined" (pg. 1681). What we need to understand is the pathophysiology to CRF(s). Another study on associated factors to CRF will not advance the science or treatment of such a distressful symptom.

    Article  PubMed  CAS  Google Scholar 

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Davis, M.P., Khoshknabi, D. & Yue, G.H. Management of fatigue in cancer patients. Current Science Inc 10, 260–269 (2006). https://doi.org/10.1007/s11916-006-0030-2

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