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Cited by 54Cancer survivorship and careCancer-related cognitive impairment studiesFrailty in Older Adults

A Practical Approach to Fatigue Management in Colorectal Cancer

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Aapro, Matti, Scotte, Florian, Bouillet, Thierry, Currow, David, Vigano, Antonio·2017·Clinical Colorectal Cancer
DOI 10.1016/j.clcc.2016.04.010
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Abstract

Cancer-related fatigue is serious and complex, as well as one of the most common symptoms experienced by patients with colorectal cancer, with the potential to compromise quality of life, activities of daily living, and ultimately survival. There is a lack of consensus about the definition of cancer-related fatigue; however, definitions have been put forward by the European Association for Palliative Care (EAPC) and the National Comprehensive Cancer Network (NCCN). Numerous cancer- and treatment-related factors can contribute to fatigue, including disease progression, comorbidities, medical complications such as anemia, side effects of other medications, and a number of physical and psychologic factors. This underlines the importance of tackling factors that may contribute to fatigue before reducing the dose of treatment. NCCN guidelines and the EAPC have proposed approaches to managing fatigue in cancer patients; however, relatively few therapeutic agents have been demonstrated to reduce fatigue in randomized controlled trials. It is recognized that physical activity produces many beneficial physiologic modifications to markers of physical performance that can help to counteract various causes of fatigue. In appropriately managed and monitored patients with colorectal cancer, emerging evidence indicates that exercise programs may have a favorable influence on cancer-related fatigue, quality of life, and clinical outcomes, and therefore may help patients tolerate chemotherapy. This review assesses fatigue in patients with colorectal cancer and proposes updates to a treatment algorithm that may help clinicians manage this common problem.

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  • Cancer-related fatigue prevalence ranges from 19% to 82% among patients post-treatment.

    “CRF prevalence ranges from 25% to more than 99% among patients who are undergoing cancer treatment (Schmidt et al. 2020), and 19% to 82% among patients post-treatment (Aapro et al. 2017), with a meta-analysis of 84 studies involving over 144,000 subjects estimating an overall pooled prevalence of 52% across the entire disease trajectory (Ma et al. 2020).”

    From Psychosocial and Integrative Oncology: Interventions Across the Disease Trajectory. (2023) · cites this paper as Aapro et al. 2017

    The Epidemiology of Fatigue section gives a different range: reported posttreatment fatigue rates vary from 17% to 53%, depending on assessment criteria. It does not report the attributed 19%–82% range. (LLM, conf=0.89)

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  1. Koornstra RH, Peters M, Donofrio S, et al. Management of fatigue in patients with cancer-a practical overview. Cancer Treat Rev 2014; 40:791-9.
  2. Pearson EJ, Morris ME, McKinstry CE. Cancer-related fatigue: a survey of health practitioner knowledge and practice. Support Care Cancer 2015; 12:3521-9.
  3. Radbruch L, Strasser F, Elsner F, et al. Fatigue in palliative care patients-an EAPC approach. Palliat Med 2008; 22:13-32.
  4. de Raaf PJ, de Klerk C, van der Rijt CC. Elucidating the behavior of physical fatigue and mental fatigue in cancer patients: a review of the literature. Psy- chooncology 2013; 22:1919-29.
  5. Prinsen H, van Dijk JP, Zwarts MJ, et al. The role of central and peripheral muscle fatigue in postcancer fatigue: a randomized controlled trial. J Pain Symptom Manage 2015; 49:173-82.
  6. Petrie KJ, Faasse K, Crichton F, et al. How common are symptoms? Evidence from a New Zealand national telephone survey. BMJ Open 2014; 4:e005374.
  7. Ranjith G. Epidemiology of chronic fatigue syndrome. Occup Med 2005; 55: 13-9.
  8. Wang XS, Zhao F, Fisch MJ, et al. Prevalence and characteristics of moderate to severe fatigue: a multicenter study in cancer patients and survivors. Cancer 2014; 120:425-32.
  9. Mota DD, Pimenta CA, Caponero R. Fatigue in colorectal cancer patients: prevalence and associated factors. Rev Lat Am Enfermagem 2012; 20:495-503.
  10. Sobrero A, Ackland S, Clarke S, et al. Phase IV study of bevacizumab in com- bination with infusional fluorouracil, leucovorin and irinotecan (FOLFIRI) in first-line metastatic colorectal cancer. Oncology 2009; 77:113-9.
  11. Cassidy J, Clarke S, Diaz-Rubio E, et al. Randomized phase III study of cape- citabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J Clin Oncol 2008; 26:2006-12.
  12. Rothenberg ML, Cox JV, Butts C, et al. Capecitabine plus oxaliplatin (XELOX) versus 5-fluorouracil/folinic acid plus oxaliplatin (FOLFOX-4) as second-line therapy in metastatic colorectal cancer: a randomized phase III noninferiority study. Ann Oncol 2008; 19:1720-6.
  13. Van Cutsem E, Tabernero J, Lakomy R, et al. Addition of aflibercept to fluo- rouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. J Clin Oncol 2012; 30:3499-506.
  14. Tveit KM, Guren T, Glimelius B, et al. Phase III trial of cetuximab with continuous or intermittent fluorouracil, leucovorin, and oxaliplatin (Nordic FLOX) versus FLOX alone in first-line treatment of metastatic colorectal cancer: the NORDIC-VII study. J Clin Oncol 2012; 30:1755-62.
  15. Peeters M, Price TJ, Cervantes A, et al. Randomized phase III study of pan- itumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colo- rectal cancer. J Clin Oncol 2010; 28:4706-13.
  16. Grothey A, Van Cutsem E, Sobrero A, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013; 381: 303-12.
  17. Li J, Qin S, Yau T, et al. O-0023 CONCUR: a randomized, double-blind, placebo-controlled phase 3 study of regorafenib monotherapy in Asian patients with previously treated metastatic colorectal cancer (MCRC). Ann Oncol 2014; 25:114-5.
  18. Zacharakis M, Xynos ID, Lazaris A, et al. Predictors of survival in stage IV metastatic colorectal cancer. Anticancer Res 2010; 30:653-60.
  19. Curt GA, Breitbart W, Cella D, et al. Impact of cancer-related fatigue on the lives of patients: new findings from the Fatigue Coalition. Oncologist 2000; 5:353-60.
  20. Kruse JL, Strouse TB. Sick and tired: mood, fatigue, and inflammation in cancer. Curr Psychiatry Rep 2015; 17:1-11.
  21. Berger AM, Mitchell SA, Jacobsen PB, et al. Screening, evaluation, and man- agement of cancer-related fatigue: ready for implementation to practice? CA Cancer J Clin 2015; 65:190-211.
  22. Kroenke K, Spitzer RL, Williams JB. The Patient Health Questionnaire-2: val- idity of a two-item depression screener. Med Care 2003; 41:1284-92.
  23. Schmidt ME, Chang-Claude J, Seibold P, et al. Determinants of long-term fa- tigue in breast cancer survivors: results of a prospective patient cohort study. Psychooncology 2015; 24:40-6.
  24. Wood LJ, Weymann K. Inflammation and neural signaling: etiologic mecha- nisms of the cancer treatment-related symptom cluster. Curr Opin Support Palliat Care 2013; 7:54-9.
  25. Österlund P, Orpana A, Elomaa I, et al. Raltitrexed treatment promotes systemic inflammatory reaction in patients with colorectal carcinoma. Br J Cancer 2002; 87:591-9.
  26. Klampfer L. Cytokines, inflammation and colon cancer. Curr Cancer Drug Targets 2011; 11:451-64.
  27. Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 1993; 259:87-91.
  28. Flower L, Gray R, Pinkney J, et al. Stimulation of interleukin-6 release by interleukin-1beta from isolated human adipocytes. Cytokine 2003; 21:32-7.
  29. Willemse PP, van der Meer RW, Burggraaf J, et al. Abdominal visceral and subcutaneous fat increase, insulin resistance and hyperlipidemia in testicular cancer patients treated with cisplatin-based chemotherapy. Acta Oncol 2014; 53: 351-60.
  30. Kantola T, Klintrup K, Vayrynen JP, et al. Stage-dependent alterations of the serum cytokine pattern in colorectal carcinoma. Br J Cancer 2012; 107:1729-36.
  31. Denicoff KD, Rubinow DR, Papa MZ, et al. The neuropsychiatric effects of treatment with interleukin-2 and lymphokine-activated killer cells. Ann Intern Med 1987; 107:293-300.
  32. Wang XS, Williams LA, Krishnan S, et al. Serum sTNF-R1, IL-6, and the development of fatigue in patients with gastrointestinal cancer undergoing che- moradiation therapy. Brain Behav Immun 2012; 26:699-705.
  33. Liu L, Mills PJ, Rissling M, et al. Fatigue and sleep quality are associated with changes in inflammatory markers in breast cancer patients undergoing chemo- therapy. Brain Behav Immun 2012; 26:706-13.
  34. De Sanctis V, Agolli L, Visco V, et al. Cytokines, fatigue, and cutaneous erythema in early stage breast cancer patients receiving adjuvant radiation therapy. Biomed Res Int 2014; 2014:523568.
  35. Wang XS, Shi Q, Shah ND, et al. Inflammatory markers and development of symptom burden in patients with multiple myeloma during autologous stem cell transplantation. Clin Cancer Res 2014; 20:1366-74.
  36. Meyers CA, Albitar M, Estey E. Cognitive impairment, fatigue, and cytokine levels in patients with acute myelogenous leukemia or myelodysplastic syndrome. Cancer 2005; 104:788-93.
  37. Clevenger L, Schrepf A, Christensen D, et al. Sleep disturbance, cytokines, and fatigue in women with ovarian cancer. Brain Behav Immun 2012; 26:1037-44.
  38. Low CA, Bovbjerg DH, Jenkins FJ, et al. Preoperative inflammatory biomarkers and neurovegetative symptoms in peritoneal carcinomatosis patients. Brain Behav Immun 2014; 42:65-8.
  39. Rich T, Innominato PF, Boerner J, et al. Elevated serum cytokines correlated with altered behavior, serum cortisol rhythm, and dampened 24-hour resteactivity patterns in patients with metastatic colorectal cancer. Clin Cancer Res 2005; 11:1757-64.
  40. Vardy J, Dhillon H, Pond G, et al. Cognitive function and fatigue after diagnosis of colorectal cancer. Ann Oncol 2014; 25:2404-12.
  41. Stone P, Hardy J, Broadley K, et al. Fatigue in advanced cancer: a prospective controlled cross-sectional study. Br J Cancer 1999; 79:1479-86.
  42. 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; 11:561-7.
  43. Kilgour RD, Vigano A, Trutschnigg B, et al. Cancer-related fatigue: the impact of skeletal muscle mass and strength in patients with advanced cancer. J Cachexia Sarcopenia Muscle 2010; 1:177-85.
  44. Miyamoto Y, Baba Y, Sakamoto Y, et al. Sarcopenia is a negative prognostic factor after curative resection of colorectal cancer. Ann Surg Oncol 2015; 22:2663-8.
  45. Lieffers J, Bathe O, Fassbender K, et al. Sarcopenia is associated with post- operative infection and delayed recovery from colorectal cancer resection surgery. Br J Cancer 2012; 107:931-6.
  46. Tan B, Brammer K, Randhawa N, et al. Sarcopenia is associated with toxicity in patients undergoing neo-adjuvant chemotherapy for oesophago-gastric cancer. Eur J Surg Oncol 2015; 41:333-8.
  47. Fuoco D, di Tomasso J, Boulos C, et al. Identifying nutritional, functional, and quality of life correlates with male hypogonadism in advanced cancer patients. Ecancermedicalscience 2015; 9:561.
  48. Campos MP, Hassan BJ, Riechelmann R, et al. Cancer-related fatigue: a review. Rev Assoc Med Bras 2011; 57:211-9.
  49. Sweeny C, Neenschwander H, Bruera E. Fatigue and asthenia. In: Doyle D, Hanks G, Cherny NI, Calman K, eds. Oxford Textbook of Palliative Medicine. 3rd ed. Oxford: Oxford University Press; 2005:560-8.
  50. Butt Z, Wagner LI, Beaumont JL, et al. Use of a single-item screening tool to detect clinically significant fatigue, pain, distress, and anorexia in ambulatory cancer practice. J Pain Symptom Manage 2008; 35:20-30.
  51. De Wit M, Boers-Doets CB, Saettini A, et al. Prevention and management of adverse events related to regorafenib. Support Care Cancer 2014; 22:837-46.
  52. Neefjes EC, van der Vorst MJ, Blauwhoff-Buskermolen S, et al. Aiming for a better understanding and management of cancer-related fatigue. Oncologist 2013; 18:1135-43.
  53. Yennurajalingam S, Bruera E. Review of clinical trials of pharmacologic in- terventions for cancer-related fatigue: focus on psychostimulants and steroids. Cancer J 2014; 20:319-24.
  54. Ruddy KJ, Barton D, Loprinzi CL. Laying to rest psychostimulants for cancer- related fatigue? J Clin Oncol 2014; 32:1865-7.
  55. Spathis A, Fife K, Blackhall F, et al. Modafinil for the treatment of fatigue in lung cancer: results of a placebo-controlled, double-blind, randomized trial. J Clin Oncol 2014; 32:1882-8.
  56. Jean-Pierre P, Morrow GR, Roscoe JA, et al. A phase 3 randomized, placebo- controlled, double-blind, clinical trial of the effect of modafinil on cancer-related fatigue among 631 patients receiving chemotherapy. Cancer 2010; 116:3513-20.
  57. 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.
  58. Del Fabbro E, Garcia JM, Dev R, et al. Testosterone replacement for fatigue in hypogonadal ambulatory males with advanced cancer: a preliminary double-blind placebo-controlled trial. Support Care Cancer 2013; 21:2599-607.
  59. Yennurajalingam S, Frisbee-Hume S, Palmer JL, et al. Reduction of cancer- related fatigue with dexamethasone: a double-blind, randomized, placebo- controlled trial in patients with advanced cancer. J Clin Oncol 2013; 31:3076-82.
  60. Lower EE, Fleishman S, Cooper A, et al. Efficacy of dexmethylphenidate for the treatment of fatigue after cancer chemotherapy: a randomized clinical trial. J Pain Symptom Manage 2009; 38:650-62.
  61. Bruera E, Yennurajalingam S, Palmer JL, et al. Methylphenidate and/or a nursing telephone intervention for fatigue in patients with advanced cancer: a random- ized, placebo-controlled, phase II trial. J Clin Oncol 2013; 31:2421-7.
  62. Moraska AR, Sood A, Dakhil SR, et al. Phase III, randomized, double-blind, placebo-controlled study of long-acting methylphenidate for cancer-related fa- tigue: North Central Cancer Treatment Group NCCTG-N05C7 trial. J Clin Oncol 2010; 28:3673-9.
  63. Monk JP, Phillips G, Waite R, et al. Assessment of tumor necrosis factor alpha blockade as an intervention to improve tolerability of dose-intensive chemo- therapy in cancer patients. J Clin Oncol 2006; 24:1852-9.
  64. Stockler MR, O'Connell R, Nowak AK, et al. Effect of sertraline on symp- toms and survival in patients with advanced cancer, but without major depression: a placebo-controlled double-blind randomised trial. Lancet Oncol 2007; 8:603-12.
  65. Cruciani RA, Zhang JJ, Manola J, et al. L-carnitine supplementation for the management of fatigue in patients with cancer: an eastern cooperative oncology group phase III, randomized, double-blind, placebo-controlled trial. J Clin Oncol 2012; 30:3864-9.
  66. Barton DL, Liu H, Dakhil SR, et al. Wisconsin ginseng (Panax quinquefolius) to improve cancer-related fatigue: a randomized, double-blind trial, N07C2. J Natl Cancer Inst 2013; 105:1230-8.
  67. Lesser GJ, Case D, Stark N, et al. A randomized double-blind, placebo-controlled study of oral coenzyme Q10 to relieve self-reported treatment related fatigue in newly diagnosed patients with breast cancer. J Support Oncol 2013; 11:31.
  68. Iwase S, Kawaguchi T, Yotsumoto D, et al. Efficacy and safety of an amino acid jelly containing coenzyme Q10 and l-carnitine in controlling fatigue in breast cancer patients receiving chemotherapy: a multi-institutional, randomized, exploratory trial (JORTC-CAM01). Support Care Cancer 2016; 24:637-46.
  69. de Oliveira Campos MP, Riechelmann R, Martins LC, et al. Guarana (Paullinia cupana) improves fatigue in breast cancer patients undergoing systemic chemo- therapy. J Altern Complement Med 2011; 17:505-12.
  70. Grothey A, George S, van Cutsem E, et al. Optimizing treatment outcomes with regorafenib: personalized dosing and other strategies to support patient care. Oncologist 2014; 19:669-80.
  71. Hayes SC, Spence RR, Galvao DA, et al. Australian Association for Exercise and Sport Science position stand: optimising cancer outcomes through exercise. J Sci Med Sport 2009; 12:428-34.
  72. Kent-Braun JA, Ng AV. Skeletal muscle oxidative capacity in young and older women and men. J Appl Physiol 2000; 89:1072-8.
  73. Rohde T, MacLean DA, Richter EA, et al. Prolonged submaximal eccentric exercise is associated with increased levels of plasma IL-6. Am J Physiol 1997; 273:E85-91.
  74. Rotter V, Nagaev I, Smith U. Interleukin-6 (IL-6) induces insulin resistance in 3T3-L1 adipocytes and is, like IL-8 and tumor necrosis factor-alpha, overex- pressed in human fat cells from insulin-resistant subjects. J Biol Chem 2003; 278: 45777-84.
  75. van Hall G, Steensberg A, Fischer C, et al. Interleukin-6 markedly decreases skeletal muscle protein turnover and increases nonmuscle amino acid utilization in healthy individuals. J Clin Endocrinol Metab 2008; 93:2851-8.
  76. Stouthard JM, Romijn JA, Van der Poll T, et al. Endocrinologic and metabolic effects of interleukin-6 in humans. Am J Physiol 1995; 268:E813-9.
  77. Schieffer B, Selle T, Hilfiker A, et al. Impact of interleukin-6 on plaque development and morphology in experimental atherosclerosis. Circulation 2004; 110:3493-500.
  78. Golbidi S, Laher I. Exercise induced adipokine changes and the metabolic syn- drome. J Diabetes Res 2014; 2014:726861.
  79. Des Guetz G, Uzzan B, Bouillet T, et al. Impact of physical activity on cancer- specific and overall survival of patients with colorectal cancer. Gastroenterol Res Pract 2013; 2013:340851.
  80. Courneya KS, Vardy J, Gill S, et al. Update on the colon health and life-long exercise change trial: a phase III study of the impact of an exercise program on disease-free survival in colon cancer survivors. Curr Colorectal Cancer Rep 2014; 10:321-8.
  81. Brown JC, Huedo-Medina TB, Pescatello LS, et al. Efficacy of exercise in- terventions in modulating cancer-related fatigue among adult cancer survivors: a meta-analysis. Cancer Epidemiol Biomarkers Prev 2011; 20:123-33.
  82. Meneses-Echávez JF, Ramírez-Vélez R, González-Jiménez E. Effects of supervised exercise on cancer-related fatigue in breast cancer survivors: a systematic review and meta-analysis. BMC Cancer 2015; 15:77.

Cited by

Sorted by citations

Authors
Aapro, M., Scotte, F., Bouillet, T., Currow, D., & Vigano, A.
Affiliations
  • Clinique de Genolier (CH)
  • Hôpital Avicenne (FR)
  • Flinders University (AU)
  • McGill University Health Centre (CA)
Corresponding author
Aapro, Matti
ORCID
Venue
Clinical Colorectal Cancer
Publisher
Elsevier BV
Published
2017-12
Volume
16
Issue
4
Pages
275-285
ISSN
1533-0028 (ISSN-L)
DOI
10.1016/j.clcc.2016.04.010
OpenAlex
W2346804067
Cited by
54
References
10
Citations by year
2026: 2 · 2025: 5 · 2024: 5 · 2023: 6 · 2022: 10 · 2021: 9 · 2020: 11 · 2019: 3 · 2018: 1 · 2016: 2
FWCI
0.20
Type
journal article
Language
en
Open access
Licence
Locations
  • Clinical Colorectal Cancer (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Flinders Academic Commons (Flinders University) (submittedVersion)
Topics
  • Health Sciences › Medicine › Oncology › Cancer survivorship and care
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
  • Health Sciences › Medicine › Geriatrics and Gerontology › Frailty in Older Adults
Keywords
cancer-related fatigue, colorectal cancer, fatigue management, exercise therapy, physical activity, quality of life, chemotherapy tolerance, anemia, comorbidities, treatment algorithm, NCCN guidelines, European Association for Palliative Care
MeSH terms
Activities of Daily Living, Antineoplastic Agents, Fatigue, Humans, Quality of Life, Colorectal Neoplasms, Exercise, Randomized Controlled Trials as Topic, Disease Progression

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