CANCER , 2003 / Volume 98 / Number 9 pp 1786 - 801

Cancer-Related Fatigue - Evolving Concepts in Evaluation and Treatment

Stasi R,  Abriani L, Beccaglia P, et al.

BACKGROUND. Although fatigue is one of the most common complaints of patients with cancer, it went unrecognized or overlooked for many years, until clinicians achieved better control over the more acute symptoms of nausea, emesis, and pain. A number of treatment-related and disease-related factors may contribute to the development of fatigue, but its physiologic basis remains poorly understood, and many proposed interventions have not been studied systematically. The lack of a standard of care for the assessment or treatment of fatigue in patients with cancer has limited research in this field. A critical appraisal of these issues is presented in this review.

Autoimmun Rev. 2009 Feb;8(4):287-91. Epub 2008 Sep 16.

Immunological aspects of chronic fatigue syndrome.

Lorusso L, Mikhaylova SV, Capelli E, Ferrari D, Ngonga GK, Ricevuti G.

Department of Neurology, Mellino Mellini Hospital, Chiari, Brescia, Italy.

Chronic fatigue syndrome (CFS) is a specific clinical condition that characterises unexplained disabling fatigue and a combination of non-specific accompanying symptoms for at least 6 months, in the absence of a medical diagnosis that would otherwise explain the clinical presentation. Other common symptoms include headaches, myalgia, arthralgia, and post-exertional malaise; cognitive difficulties, with impaired memory and concentration; unrefreshing sleep; and mood changes. Similar disorders have been described for at least two centuries and have been differently named neurasthenia, post-viral fatigue, myalgic encephalomyelitis and chronic mononucleosis.

Scand J Immunol. 1994 Dec;40(6):601-8

Immunological abnormalities in patients with chronic fatigue syndrome.

Tirelli U, Marotta G, Improta S, Pinto A.

CFS Unit, Division of Medical Oncology and AIDS, Centro di Riferimento Oncologico (CRO), Aviano, Italy.

Between January 1991 and January 1993, 265 patients who fulfilled the CDC criteria of the working case definition of Chronic Fatigue Syndrome (CFS) have been observed at our Institution and submitted for clinical and laboratory evaluation. One hundred and sixty-three patients were females and 102 males, the median age was 35 years (range 4-55 years); all patients reported profound and prolonged fatigue, lasting for a median of 3 years (range 6 months-10 years), preceded or accompanied at appearance by fever in 185 cases, and neuropsychologic problems including inability to concentrate, difficulty in thinking, confusion, irritability, forgetfulness, and depression.

Ciba Found Symp. 1993;173:176-87; discussion 187-92

Immunity and the pathophysiology of chronic fatigue syndrome.

Lloyd AR, Wakefield D, Hickie I.

Laboratory of Molecular Immunoregulation, National Cancer Institute, Frederick, MD 21702-1201.

The pathophysiology of chronic fatigue syndrome (CFS) remains unknown. The syndrome often follows a recognized or presumed infection and the disorder may therefore result from a disordered immune response to a precipitating infection or antigenic challenge. Abnormalities of both humoral and cellular immunity have been demonstrated in a substantial proportion of patients with CFS. The most consistent findings are of impaired lymphocyte responses to mitogen and reduced natural killer cell cytotoxicity.

Med Hypotheses. 1999 Oct;53(4):347-9.

Competition for glutathione precursors between the immune system and the skeletal muscle: pathogenesis of chronic fatigue syndrome.

Bounous G, Molson J.

Department of Surgery, McGill University, and Medical Research Council of Canada.

The chronic fatigue syndrome (CFS) is typically associated or follows a recognized or presumed infection. Abnormalities of both humoral and cellular immunity have been demonstrated in a substantial proportion of patients with CFS. The most consistent findings are of impaired lymphocyte responses to mitogen. As an antioxidant, glutathione (GSH) is essential for allowing the lymphocyte to express its full potential without being hampered by oxiradical accumulation. Hence, protracted challenge of the immunocytes may lead to cellular GSH depletion.

Autoimmun Rev. 2009 Feb;8(4):287-91.

Immunological aspects of chronic fatigue syndrome.

Lorusso L, Mikhaylova SV, Capelli E, Ferrari D, Ngonga GK, Ricevuti G.

Department of Neurology, Mellino Mellini Hospital, Chiari, Brescia, Italy.

Chronic fatigue syndrome (CFS) is a specific clinical condition that characterises unexplained disabling fatigue and a combination of non-specific accompanying symptoms for at least 6 months, in the absence of a medical diagnosis that would otherwise explain the clinical presentation. Other common symptoms include headaches, myalgia, arthralgia, and post-exertional malaise; cognitive difficulties, with impaired memory and concentration; unrefreshing sleep; and mood changes. Similar disorders have been described for at least two centuries and have been differently named neurasthenia, post-viral fatigue, myalgic encephalomyelitis and chronic mononucleosis.

Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 22, No 14S (July 15 Supplement), 2004: 8115
© 2004 American Society of Clinical Oncology

Clinical predictors of severe fatigue in solid tumor patients seeking acute care

R. Valdres, E. Manzullo and C. P. Escalante

U Texas M. D. Anderson Cancer Center, Houston, TX

Background: Fatigue is the most common symptom of cancer patients and has been described in various populations. Our objectives are to describe solid tumor patients (STP) and clinical factors associated with severe fatigue (defined as worst fatigue in past 24 hours 7/10) in an acute care setting and to determine whether certain clinical factors available during the emergency center (EC) visit identify patients with severe fatigue.

The positive effect of the psychostimulant modafinil on fatigue from cancer that persists after treatment is completed

G. R. Morrow, L. J. Gillies, J. T. Hickok, J. A. Roscoe, D. Padmanaban and J. J. Griggs

Univ of Rochester Cancer Ctenter, Rochester, NY

Background: Fatigue is the most common adverse effect reported by patients undergoing cancer treatment. Several large studies have shown up to 90% may experience fatigue sometime during treatment. Approximately a quarter report that their fatigue persists for months or even years beyond cancer treatment. Control of this debilitating side effect remains inadequate.

A randomized control study on the effects of prescriptive exercise on lean mass and fatigue in breast cancer patients undergoing treatment

C. Battaglini and C. A. Dennehy

The University of North Carolina, Chapel Hill, NC; Navitas Cancer Rehabilitation Centers, Westminster, CO

Background: Loss of lean mass during cancer treatment has been correlated with increases in fatigue (F) levels. Exercise is related to decreases treatment related fatigue and has been shown to thwart muscle loss.

A randomized trial of home-based exercise for patients receiving aggressive treatment and epoetin alfa for multiple myeloma: Hemoglobin (Hb), transfusion, fatigue and performance as outcomes

E. A. Coleman, E. Anaissie, S. K. Coon, C. B. Stewart, J. Shaw and B. Barlogie

University of Arkansas for Medical Sciences, Little Rock, AR

Background: Over 60% of patients with multiple myeloma (MM) are anemic (Hb < 12 g/dL) at diagnosis. Nearly all become anemic during aggressive treatment for MM and many require red blood cell (RBC) transfusions. Anemia can contribute to fatigue, the most common and often the most distressing symptom for patients with cancer.

A prospective study evaluating the relationship between fatigue and patient satisfaction in advanced cancer

R. D. Levin, M. Daehler, C. G. Lis, D. Gupta, T. Wodek, J. F. Grutsch, J. Granick, S. Williams, D. L. Citrin and R. Neelam

Cancer Treatment Centers of America, Zion, IL

Background: Fatigue is the most common and disabling symptoms experienced by cancer patients. No study has prospectively quantified the relationship between fatigue and patient satisfaction (PS) in advanced cancer. We therefore assessed this relationship before the start of chemotherapy and at 3 and 6 months after treatment at our integrative cancer treatment center.

Donepezil for cancer-related fatigue: A double-blind, randomized, placebo-controlled study

E. Bruera, B. El Osta, V. Valero, L. Driver, J. Palmer, B. Pei, L. Shen and V. Poulter

M. D. Anderson Cancer Center, Houston, TX

Background: Fatigue is the most frequent symptom in advanced cancer. No standard treatment is available. We previously found that open-label donepezil significantly improved fatigue by day 3 and 7 in patients (pts) on opioids for cancer pain (Fisch et al, ASCO 2003). The purpose of this study was to compare donepezil (D) with placebo (P) for fatigue in pts with advanced cancer.

Assessing simple measures of patient-reported (PR) fatigue for oncology clinical trials: A pooled analysis of 3,915 patients

H. Liu, J. A. Sloan, D. J. Sargent, D. V. Satele, P. L. Schaefer, M. Y. Halyard, A. Grothey, Y. I. Garces, P. D. Brown and J. C. Buckner

Mayo Clinic, Rochester, Rochester, MN; Toledo Clinic, Toledo, OH; Mayo Clinic, Scottsdale, AZ

Background: Fatigue is a prevalent and debilitating symptom reported by cancer patients (pts) which compromises a pt's quality of life (QOL). This study examined the relationship between PR fatigue and QOL as well as cancer-related symptoms (CRS) in 43 North Central Cancer Treatment Group and Mayo Clinic Cancer Center clinical trials.

Effect of complementary alternative medical (CAM) therapy on pain and fatigue in pancreatic cancer patients

T. C. Birdsall, R. D. Levin, L. Alschuler, M. Daehler, S. M. Birdsall, J. Martin, L. Dounaevskaia, C. G. Lis and D. P. Braun

Cancer Treatment Centers of America, Zion, IL

Background: Pain and fatigue are frequent, difficult to manage, and negatively impact quality of life (QOL) in pancreatic adenocarcinoma patients (PCpts) causing some to seek CAM therapy in place of or in conjunction with conventional analgesics. But the efficacy of CAM on pain and fatigue has not been adequately tested in controlled trials. We employed an alternative strategy by abstracting pain and fatigue scores from the EORTC-QLQ-C30 questionnaire administered to PCpts treated at Midwestern Regional Medical Center, an integrative oncology center offering conventional and CAM treatment.

Perception of cancer-related fatigue: Results of a patient survey

N. Díaz, S. Menjón, C. Rolfo, P. García-Alfonso, J. Carulla, A. Magro, J. Miramón, C. A. Rodríguez, E. Baró and J. A. Gasquet

H. San Juan de Alicante, Alicante, Spain

Background: Fatigue is one of the cancer-related symptoms that has the greatest impact on patients’ lives. This survey was designed to better understand the functional and psychological impact of fatigue and to determine, according to the patient’s perception, the load of fatigue relative to other symptoms.