Skip to main content
SpringerLink
Log in

Does Effective Management of Sleep Disorders Reduce Cancer-Related Fatigue?

  • Review Article
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Cancer and cancer therapy are often associated with symptoms such as fatigue and sleep disturbances, before, during and after therapy. These symptoms of fatigue and poor sleep often occur in parallel having a significant impact on the physical functioning of patients with cancer. A strong correlation between cancer-related fatigue (CRF) and sleep has been observed in several studies, suggesting that they may be reciprocally related. The co-clustering of these symptoms suggests that they may have similar underlying aetiology and that treatments targeting either symptom may positively affect the other. Studies examining these clusters have shown that these symptoms often co-vary together. The potential mechanisms that link the relationship between insomnia and CRF are intriguing but require further investigation. Despite the high prevalence of insomnia and the often bidirectional relationship between poor sleep and fatigue, there are limited data to support the use of sleep management interventions as a means to reduce fatigue in patients with cancer. Assessment of the available evidence across trials is complicated by different study designs, patient selection criteria, stage of cancer treatment and by the nature of the interventions studied. Improvements from baseline in both sleep parameters and CRF have been documented in a limited number of studies, including two randomized-controlled trials using cognitive behavioural therapy for insomnia (CBT-I). In contrast, the efficacy of pharmacological therapies in reducing both insomnia and CRF is largely lacking. Clearly, treating clinically significant insomnia is likely to have benefits for the patient with cancer and for those who are recovering from cancer. In particular, pharmacotherapies for insomnia, singly or in combination with CBT-I, should be evaluated in multicentre randomized clinical trials to examine their efficacy in improving sleep quality and reducing associated CRF.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Table II

Similar content being viewed by others

References

  1. Kuo HH, Chiu MJ, Liao WC, et al. Quality of sleep and related factors during chemotherapy in patients with stage I/II breast cancer. J Formos Med Assoc 2006; 105: 64–9

    Article  PubMed  Google Scholar 

  2. Kenefick AL. Patterns of symptom distress in older women after surgical treatment for breast cancer. Oncol Nurs Forum 2006; 33: 327–35

    Article  PubMed  Google Scholar 

  3. Ahlberg K, Ekman T, Gaston-Johansson F. The experience of fatigue, other symptoms and global quality of life during radiotherapy for uterine cancer. Int J Nurs Stud 2005; 42: 377–86

    Article  PubMed  Google Scholar 

  4. Curran SL, Beacham AO, Andrykowski MA. Ecological momentary assessment of fatigue following breast cancer treatment. J Behav Med 2004; 27: 425–44

    Article  PubMed  Google Scholar 

  5. 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

    Article  PubMed  Google Scholar 

  6. National Comprehensive Cancer Network. Cancer-related fatigue: NCCN clinical practice guidelines in oncology. 2008 (cited 17 December 2008). Available from: http://www.nccn.org/professionals/physician_gls/PDF/fatigue.pdf [Accessed 2009 Feb]

  7. Chow E, Fan G, Hadi S, et al. Symptom clusters in cancer patients with brain metastases. Clin Oncol 2008; 20: 76–82

    Article  CAS  Google Scholar 

  8. Kim SH, Son BH, Hwang SY, et al. Fatigue and depression in disease-free breast cancer survivors: prevalence, correlates, and association with quality of life. J Pain Symptom Manage 2008; 35: 644–55

    Article  PubMed  Google Scholar 

  9. Okuyama T, Akechi T, Kugaya A, 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

    Article  PubMed  CAS  Google Scholar 

  10. Liu L, Fiorentino L, Natarajan L, et al. Pre-treatment symptom cluster in breast cancer patients is associated with worse sleep, fatigue and depression during chemotherapy. Psychooncology 2009; 18: 187–94

    Article  PubMed  Google Scholar 

  11. Given B, Given C, Azzouz F, et al. Physical functioning of elderly cancer patients prior to diagnosis and following initial treatment. Nurs Res 2001; 50: 222–32

    Article  PubMed  CAS  Google Scholar 

  12. Redeker NS, Lev EL, Ruggiero J. Insomnia, fatigue, anxiety, depression, and quality of life of cancer patients undergoing chemotherapy. Sch Inq Nurs Pract 2000; 14: 275–90; discussion 91-8

    PubMed  CAS  Google Scholar 

  13. Dimsdale JE, Ancoli-Israel S, Ayalon L, et al. Taking fatigue seriously, II: variability in fatigue levels in cancer patients. Psychosomatics 2007; 48: 247–52

    Article  PubMed  Google Scholar 

  14. Davidson JR, MacLean AW, Brundage MD, et al. Sleep disturbance in cancer patients. Soc Sci Med 2002; 54: 1309–21

    Article  PubMed  Google Scholar 

  15. Bower JE, Ganz PA, Aziz N. Altered cortisol response to psychologic stress in breast cancer survivors with persistent fatigue. Psychosom Med 2005; 67: 277–80

    Article  PubMed  Google Scholar 

  16. Bower JE, Ganz PA, Aziz N, et al. Fatigue and proin-flammatory cytokine activity in breast cancer survivors. Psychosom Med 2002; 64: 604–11

    PubMed  Google Scholar 

  17. Bower JE, Ganz PA, Dickerson SS, et al. Diurnal cortisol rhythm and fatigue in breast cancer survivors. Psycho-neuroendocrinology 2005; 30: 92–100

    Article  CAS  Google Scholar 

  18. Jager A, Sleijfer 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

    Article  PubMed  CAS  Google Scholar 

  19. 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: 1757–64

    Article  PubMed  CAS  Google Scholar 

  20. Roscoe JA, Morrow GR, Hickok JT, et al. Temporal interrelationships among fatigue, circadian rhythm and depression in breast cancer patients undergoing chemotherapy treatment. Support Care Cancer 2002; 10: 329–36

    Article  PubMed  Google Scholar 

  21. Ryan JL, Carroll JK, Ryan EP, et al. Mechanisms of cancer-related fatigue. Oncologist 2007; 12 Suppl. 1: 22–34

    Article  Google Scholar 

  22. Ancoli-Israel S, Moore PJ, Jones V. The relationship between fatigue and sleep in cancer patients: a review. Eur J Cancer Care (Engl) 2001; 10: 245–55

    Article  CAS  Google Scholar 

  23. Sela RA, Watanabe S, Nekolaichuk CL. Sleep disturbances in palliative cancer patients attending a pain and symptom control clinic. Palliat Support Care 2005; 3: 23–31

    Article  PubMed  Google Scholar 

  24. Savard J, Simard S, Blanchet J, et al. Prevalence, clinical characteristics, and risk factors for insomnia in the context of breast cancer. Sleep 2001; 24: 583–90

    PubMed  CAS  Google Scholar 

  25. Roscoe JA, Kaufman ME, Matteson-Rusby SE, et al. Cancer-related fatigue and sleep disorders. Oncologist 2007; 12 Suppl. 1:35–42

    Article  PubMed  Google Scholar 

  26. Barsevick AM. The elusive concept of the symptom cluster. Oncol Nurs Forum 2007; 34: 971–80

    Article  PubMed  Google Scholar 

  27. Chen ML, Chang HK. Physical symptom profiles of depressed and nondepressed patients with cancer. Palliat Med 2004; 18:712–18

    Article  PubMed  Google Scholar 

  28. Sateia MJ, Lang BJ. Sleep and cancer: recent developments. Curr Oncol Rep 2008; 10: 309–18

    Article  PubMed  Google Scholar 

  29. Stone P, Richards M, A’Hern R, et al. Fatigue in patients with cancers of the breast or prostate undergoing radical radiotherapy. J Pain Symptom Manage 2001; 22: 1007–15

    Article  PubMed  CAS  Google Scholar 

  30. Theobald DE. Cancer pain, fatigue, distress, and insomnia in cancer patients. Clin Cornerstone 2004; 6 Suppl. 1D: S15–21

    Article  PubMed  Google Scholar 

  31. Weitzner MA, Moncello J, Jacobsen PB, et al. A pilot trial of paroxetine for the treatment of hot flashes and associated symptoms in women with breast cancer. J Pain Symptom Manage 2002; 23: 337–45

    Article  PubMed  CAS  Google Scholar 

  32. Yennurajalingam S, Palmer JL, Zhang T, et al. Association between fatigue and other cancer-related symptoms in patients with advanced cancer. Support Care Cancer 2008; 16: 1125–30

    Article  PubMed  Google Scholar 

  33. Carpenter JS, Storniolo AM, Johns S, et al. Randomized, double-blind, placebo-controlled crossover trials of venla-faxine for hot flashes after breast cancer. Oncologist 2007; 12: 124–35

    Article  PubMed  CAS  Google Scholar 

  34. Stearns V, Slack R, Greep N, et al. Paroxetine is an effective treatment for hot flashes: results from a prospective randomized clinical trial. J Clin Oncol 2005; 23: 6919–30

    Article  PubMed  CAS  Google Scholar 

  35. Stockler MR, O’Connell R, Nowak AK, 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

    Article  PubMed  CAS  Google Scholar 

  36. Kangas M, Bovbjerg DH, Montgomery GH. Cancer-related fatigue: a systematic and meta-analytic review of non-pharmacological therapies for cancer patients. Psychol Bull 2008; 134: 700–41

    Article  PubMed  Google Scholar 

  37. Fiorentino L, Ancoli-Israel S. Insomnia and its treatment in women with breast cancer. Sleep Med Rev 2006; 10: 419–29

    Article  PubMed  Google Scholar 

  38. Ancoli-Israel S. Sleep and fatigue in cancer patents. In: Kryger MH, Roth T, Dement WC, editors. Principles and practice of sleep medicine. 4th ed. Philadelphia: Saunders, 2005: 1218–24

    Chapter  Google Scholar 

  39. Minton O, Stone P, Richardson A, et al. Drug therapy for the management of cancer related fatigue. Cochrane Database Syst Rev 2008; (1): CD006704

  40. Minton O, Richardson A, Sharpe M, et al. A systematic review and meta-analysis of the pharmacological treatment of cancer-related fatigue. J Natl Cancer Inst 2008; 100: 1155–66

    Article  PubMed  CAS  Google Scholar 

  41. Berger AM, Parker KP, Young-McCaughan S, et al. Sleep wake disturbances in people with cancer and their care-givers: state of the science. Oncol Nurs Forum 2005; 32: E98–126

    Article  PubMed  Google Scholar 

  42. Hirst A, Sloan R. Benzodiazepines and related drugs for insomnia in palliative care. Cochrane Database Syst Rev 2002; (4): CD003346

  43. Paltiel O, Marzec-Boguslawska A, Soskolne V, et al. Use of tranquilizers and sleeping pills among cancer patients is associated with a poorer quality of life. Qual Life Res 2004; 13: 1699–706

    Article  PubMed  CAS  Google Scholar 

  44. Dirksen SR, Epstein DR. Efficacy of an insomnia intervention on fatigue, mood and quality of life in breast cancer survivors. J Adv Nurs 2008; 61: 664–75

    Article  PubMed  Google Scholar 

  45. Espie CA, Fleming L, Cassidy J, et al. Randomized controlled clinical effectiveness trial of cognitive behavior therapy compared with treatment as usual for persistent insomnia in patients with cancer. J Clin Oncol 2008; 26: 4651–8

    Article  PubMed  Google Scholar 

  46. Savard J, Simard S, Ivers H, et al. Randomized study on the efficacy of cognitive-behavioral therapy for insomnia secondary to breast cancer, part I: sleep and psychological effects. J Clin Oncol 2005; 23: 6083–96

    Article  PubMed  Google Scholar 

  47. Quesnel C, Savard J, Simard S, et al. Efficacy of cognitive-behavioral therapy for insomnia in women treated for nonmetastatic breast cancer. J Consult Clin Psychol 2003; 71: 189–200

    Article  PubMed  Google Scholar 

  48. Simeit R, Deck R, Conta-Marx B. Sleep management training for cancer patients with insomnia. Support Care Cancer 2004; 12: 176–83

    Article  PubMed  Google Scholar 

  49. Davidson JR, Waisberg JL, Brundage MD, et al. Non-pharmacologic group treatment of insomnia: a preliminary study with cancer survivors. Psychooncology 2001; 10: 389–97

    Article  PubMed  CAS  Google Scholar 

  50. Berger AM, Kuhn BR, Farr LA, et al. Behavioral therapy intervention trial to improve sleep quality and cancer-related fatigue. Psychooncology 2009; 18(6): 634–46

    Article  PubMed  Google Scholar 

  51. Carlson LE, Garland SN. Impact of mindfulness-based stress reduction (MBSR) on sleep, mood, stress and fatigue symptoms in cancer outpatients. Int J Behav Med 2005; 12: 278–85

    Article  PubMed  Google Scholar 

  52. Williams SA, Schreier AM. The effect of education in managing side effects in women receiving chemotherapy for treatment of breast cancer. Oncol Nurs Forum 2004; 31: E16–23

    Article  PubMed  Google Scholar 

  53. Payne JK, Held J, Thorpe J, et al. Effect of exercise on biomarkers, fatigue, sleep disturbances, and depressive symptoms in older women with breast cancer receiving hormonal therapy. Oncol Nurs Forum 2008; 35: 635–42

    Article  PubMed  Google Scholar 

  54. Fiorentino L, McQuaid JR, Liu L, et al. Individual cognitive behavioral therapy for insomnia in breast cancer survivors: A randomized controlled crossover pilot study. Journal of the Nature and Science of Sleep 2009; in press

  55. Smith MT, Perlis ML, Park A, et al. Comparative meta-analysis of pharmacotherapy and behavior therapy for persistent insomnia. Am J Psychiatry 2002; 159: 5–11

    Article  PubMed  Google Scholar 

  56. Grossman P, Niemann L, Schmidt S, et al. Mindfulness-based stress reduction and health benefits. A meta-analysis. J Psychosom Res 2004; 57: 35–43

    Article  Google Scholar 

  57. Ehsanullah RS, Galloway DB, Gusterson FR, et al. A double-blind crossover study of diazepam rectal suppositories, 5 mg and 10mg, for sedation in patients with advanced malignant disease. Pharmatherapeutica 1982; 3: 215–20

    PubMed  CAS  Google Scholar 

  58. Matsuo N, Morita T. Efficacy, safety, and cost effectiveness of intravenous midazolam and flunitrazepam for primary insomnia in terminally ill patients with cancer: a retrospective multicenter audit study. J Palliat Med 2007; 10: 1054–62

    Article  PubMed  Google Scholar 

  59. Kim SW, Shin IS, Kim JM, et al. Effectiveness of mirtazapine for nausea and insomnia in cancer patients with depression. Psychiatry Clin Neurosci 2008; 62: 75–83

    Article  PubMed  CAS  Google Scholar 

  60. Stearns V, Isaacs C, Rowland J, et al. A pilot trial assessing the efficacy of paroxetine hydrochloride (Paxil) in controlling hot flashes in breast cancer survivors. Ann Oncol 2000; 11: 17–22

    Article  PubMed  CAS  Google Scholar 

  61. Grassi L, Biancosino B, Marmai L, et al. Effect of reboxetine on major depressive disorder in breast cancer patients: an open-label study. J Clin Psychiatry 2004; 65: 515–20

    Article  PubMed  CAS  Google Scholar 

  62. Loprinzi CL, Pisansky TM, Fonseca R, et al. Pilot evaluation of venlafaxine hydrochloride for the therapy of hot flashes in cancer survivors. J Clin Oncol 1998; 16: 2377–81

    PubMed  CAS  Google Scholar 

  63. Morrow GR, Gillies LJ, Hickok JT, et al. The positive effect of the psychostimulant modafinil on fatigue from cancer that persists after treatment is completed [abstract no. 8012]. J Clin Oncol 2005; 23 (16 Suppl. Pt 1): 732S

    Google Scholar 

  64. Perez DG, Loprinzi CL, Barton DL, et al. Pilot evaluation of mirtazapine for the treatment of hot flashes. J Support Oncol 2004; 2: 50–6

    PubMed  CAS  Google Scholar 

  65. Carlson LE, Speca M, Patel KD, et al. Mindfulness-based stress reduction in relation to quality of life, mood, symptoms of stress and levels of cortisol, dehydroepiandrosterone sulfate (DHEAS) and melatonin in breast and prostate cancer outpatients. Psychoneuroendocrinology 2004; 29: 448–74

    Article  PubMed  CAS  Google Scholar 

  66. Miller AH, Ancoli-Israel S, Bower JE, et al. Neuroendocrine-immune mechanisms of behavioral comorbidities in patients with cancer. J Clin Oncol 2008; 26: 971–82

    Article  PubMed  CAS  Google Scholar 

  67. Mills PJ, Parker B, Dimsdale JE, et al. The relationship between fatigue and quality of life and inflammation during anthracycline-based chemotherapy in breast cancer. Biological Psychology 2005; 69: 85–96

    Article  PubMed  Google Scholar 

  68. Bruera E, Fainsinger RL, Schoeller T, et al. Rapid discontinuation of hypnotics in terminal cancer patients: a prospective study. Ann Oncol 1996; 7: 855–6

    Article  PubMed  CAS  Google Scholar 

  69. Teegarden BR, Al Shamma H, Xiong Y. 5-HT(2A) inverse-agonists for the treatment of insomnia. Curr Top Med Chem 2008; 8: 969–76

    Article  PubMed  CAS  Google Scholar 

  70. De Martino G, La Regina G, La Torre F, et al. Chiral resolution and binding study of 1,3,4,14b-tetrahydro-2,10-dimethyl-2H,10H-pyrazino[2,1-d]pyrrolo[1,2-b] [1,2,5]benzo-triazepine (10-methyl-10-azaaptazepine) and 2-methyl-1,3,4, 14b-tetrahydro-2H-pyrazino[2, 1-d]pyrrolo[1,2-b] [1,2,5]benzo-thiadiazepine 10,10-dioxide (tiaaptazepine). Farmaco 2005; 60: 931–7

    Article  PubMed  Google Scholar 

  71. Kast RE. Mirtazapine may be useful in treating nausea and insomnia of cancer chemotherapy. Support Care Cancer 2001; 9: 469-70

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The discussions that took place during a workshop at the 6th annual meeting of The International Sleep Disorders Forum: The Art of Good Sleep, held in 2008, contributed to the preparation of this article. The authors would like to thank the following individuals who attended the workshop and contributed to the discussions that have informed the content of this article: Shigeru Chiba (Japan), Colin Espie (UK), Christian Guilleminault (USA), Max Hirshkowitz (USA), James Krueger (USA), Jesus Paniagua (Spain), Alexandros Vgontzas (USA) and Michael Wiegand (Germany). The authors would like to thank Sohita Dhillon and Julian Martins from Wolters Kluwer Pharma Solutions for providing medical writing support in the preparation of this article. This assistance was supported by sanofi-aventis. The International Sleep Disorders Forum: The Art of Good Sleep 2008 was funded by sanofi-aventis.

Declaration of conflicts of interest: Phyllis C. Zee has served as a consultant and on the scientific advisory board for Boeringer-Ingelheim, Cephalon, Jazz, Merck, Phillips, sanofi-aventis, Takeda and Zeo. Northwestern University has received educational and research grants from Takeda North America. Phyllis C. Zee has also received royalties from Lippincott, Williams and Wilkins. Sonia Ancoli-Israel has served as a consultant and on the scientific advisory board for Ferring Pharmaceuticals Inc., GlaxoSmithKline, Orphagen Pharmaceuticals, Pfizer, Respironics, sanofi-aventis, Sepracor, Inc., Schering-Plough. Sonia Ancoli-Israel is supported in part by NCI CA112035.

Author information

Authors and Affiliations

  1. Northwestern University’s Feinberg School of Medicine, 710 N. Lake Shore Drive, Suite 521, Chicago, Illinois, 60611, USA

    Phyllis C. Zee MD, PhD

  2. University of California, San Diego, La Jolla, California, USA

    Sonia Ancoli-Israel

Authors
  1. Phyllis C. Zee MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sonia Ancoli-Israel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Phyllis C. Zee MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zee, P.C., Ancoli-Israel, S. Does Effective Management of Sleep Disorders Reduce Cancer-Related Fatigue?. Drugs 69 (Suppl 2), 29–41 (2009). https://doi.org/10.2165/11531140-000000000-00000

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/11531140-000000000-00000

Keywords

Search

Navigation