Management of Fatigue in the Cancer Patient

March 1, 2002

The Lesage and Portenoy article fulfills several important purposes. First, the authors remind us of the critical need to become more systematic and diligent in assessing and monitoring fatigue, a potentially debilitating symptom that is now recognized as the most common adverse effect experienced by cancer patients undergoing active treatment.[1] In the assessment of fatigue, the authors acknowledge that "the gold standard of evaluation is the patient’s self-report."

The Lesage and Portenoy article fulfillsseveral important purposes. First, the authors remind us of the critical need tobecome more systematic and diligent in assessing and monitoring fatigue, apotentially debilitating symptom that is now recognized as the most commonadverse effect experienced by cancer patients undergoing active treatment.[1] Inthe assessment of fatigue, the authors acknowledge that "the gold standardof evaluation is the patient’s self-report."

Several valid and reliable single- and multiple-item intensityscales can be used to quickly screen patients for this important symptom.[2-5]Given that these scales—particularly the
0-10 verbal and numeric rating scales—are easy to complete and score, thereis no reason that fatigue should go unrecognized or unmonitored. Indeed, theassessment, monitoring, and treatment of fatigue are now expected aspects ofstandard oncologic care.[1]

As a result, each practice setting must immediately work towardincorporating an intensity scale for measuring fatigue and determining responseto treatment into its documentation and patient-completed history forms.Evidence-based fatigue practice guidelines also need to be incorporated intoclinical practice.

Fatigue Intensity and Screening

Two studies have documented marked declines in physicalfunctioning in cancer patients with a fatigue intensity score of 7 on a scale of0 to 10.[6,7] In addition, a recently completed international study validatedthe following intensity categories for fatigue in breast and prostate cancerpatients receiving active therapy using the multidimensional Piper Fatigue Scale’stotal fatigue score: none (0), mild (1-3), moderate (4-6), and severe (7-10).[B.F.Piper et al, unpublished data.] Since these intensity levels constitute the bestavailable data for evidence-based practice guidelines, they can serve as"triggers" to alert health-care professionals of the need(particularly in patients at moderate to severe levels) to conduct a morecomprehensive and multidimensional assessment followed by the initiation ofprimary and symptomatic treatments, either alone or in combination, asclinically indicated and suggested by Lesage and Portenoy.

In addition, it is important to recognize that all patients needto be screened for fatigue at baseline, as they undergo their initial diagnosticwork-up for cancer. Cancer patients may experience fatigue (as measured incomparisons with controls) even before treatment begins.[8] When fatigueprecedes the initial cancer diagnosis, treatment of fatigue may need to beinstituted earlier in the course of the illness (and its treatment) than mightnormally be expected. It has been posited that earlier therapy for fatigue maybe more likely to prevent the condition from becoming chronic, although thetiming and effectiveness of fatigue interventions in general need more study.

Screening should be performed repeatedly at all subsequenttreatment-related and follow-up visits. Patient self-report diaries can also beused for this purpose. Chronic fatigue, a possible late effect of cancer and/orits treatment, has been documented in several cancer survivor studies. Theincidence and prevalence rates for survivor fatigue range from 17%, when strictICD-10 diagnostic criteria (International Classification of Diseases-10threvision) are applied, to as high as 80% when less stringent criteria areapplied.[9] Other areas in which fatigue incidence/prevalence rates and responseto treatment have not been well-studied include patients receiving palliative orterminal care and those receiving preventive care because they are at high riskfor cancer or its recurrence.

Treatment Guide

The authors’ inclusion of the algorithm to evaluate and treatfatigue is valuable; other groups have proposed similar algorithms.[1] Althoughsuch evidence-based algorithms and diagnostic criteria[9] need further testingand refinement, they can be used in the clinical setting to guide currentpractice.

The authors briefly discuss the primary, symptomaticpharmacologic and nonpharmacologic therapies for fatigue. An important area oftreatment that needs to be emphasized further is that fatigue may be accompaniedby other symptoms such as pain and insomnia. Increased attention in practice andresearch is now being given to not only identifying the symptoms that mostfrequently cluster with fatigue and under what circumstances,[10] but also tothe hypothesis that effective treatment of these symptoms, may indirectly andeffectively treat fatigue as well.

In addition, two recently published studies suggest thateffective treatment of anemia in cancer patients with recombinant humanerythropoietin (Epogen, Procrit) may not only be linked to improvements infatigue and quality of life but also to improved survival rates in those whorespond to the drug.[11,12] For the most current on-line evidence-based practiceguidelines for anemia treatment in cancer patients, readers are referred toSabbatini, Cella, Chanan-Kahn, et al’s version 1.2002 guidelines availablefrom the National Comprehensive Cancer Network (NCCN).[13] There is also arecently published article that summarizes what is known about the use ofmethylphenidate in palliative care that may be helpful to readers.[14]

Article Limitations

On the whole, however, I found the article somewhatdisappointing in that it offered no new insights or in-depth discussions aboutthe posited relationship between selected variables (such as abnormalities inenergy metabolism, neuromuscular dysfunction, sleep disorders, and depression)and fatigue. Granted, only a limited number of descriptive studies andrandomized clinical trials conducted in cancer populations have treated fatiguesuccessfully and described the relationship between the variables that aregenerally assumed to be associated with fatigue. This dearth is wellacknowledged by the authors.

Despite the fact that the authors offer a decent overview offatigue in cancer and provide readers with an excellent algorithm for theevaluation and treatment of fatigue, the article could have been strengthened intwo major areas. The review of the literature and the articles cited could havebeen more in-depth and less reliant on textbook citations. In several areas, nocitations other than the authors’ opinions were presented. Similarly, a morein-depth discussion of the relationships that are posited to exist betweenspecific variables and cancer-related fatigue would have been more helpful.

For example, the cytokine discussion is particularly limiteddespite the fact that this is an area of intense interest and investigation.[15]Fatigue is well known to be associated with the exogenous administration of manybiological therapies,[16,17] but a discussion of how to tease out the in vivomeasurement of these cytokines and how to correlate these measurements withfatigue would have been helpful.

In addition, the article’s citations and discussion of thepositive effects of aerobic exercise on fatigue is particularly cursory andfails to note the growing body of evidence in support of aerobic exercise inearly-stage breast cancer and in cancer patients who have received bone/stemcell transplants for their malignancies.[1] It was also a surprise to see thatthe previously published evidence-based NCCN practice guidelines on both cancerfatigue and psychological distress were not mentioned in this article.[1,18]Revised guidelines on these and other subjects are available at the NCCN website(www.nccn.org).

Conclusions

In summary, the authors have provided us with a useful overviewof what is currently known about cancer-related fatigue and have presentedhealth-care professionals with a treatment-based algorithm for fatigue that canbe used in clinical practice. The article may be more helpful to clinicians andresearchers who are new to the subject of fatigue than to those with moreexperience in cancer-related fatigue. The article could have been strengthenedby a more thorough review of the literature and more in-depth discussion of howparticular variables are hypothesized to be related to fatigue.

References:

1. Mock V, Atkinson A, Barsevick A, et al: NCCN cancer-relatedfatigue guideline. The Complete Library of NCCN Oncology Practice Guidelines(CD-ROM), Rockledge, Pa, NCCN, 2001. To view the most recent version of theguideline on-line, go to http://www.nccn.org.

2. Meek PM, Nail LM, Barsevick A, et al: Psychometric testing offatigue instruments for use with cancer patients. Nurs Res 49(4):181-190, 2000.

3. Mendoza TR, Wang XS, Cleeland CS, et al: The rapid assessmentof fatigue severity in cancer patients: Use of the Brief Fatigue Inventory.Cancer 85(5):1186-1196, 1999.

4. Piper BF: Measuring fatigue, in Frank-Stromborg M, Olsen SJ (eds):Instruments for Clinical Health-Care Research, 2nd ed, pp 482-496. Boston, Jones& Bartlett, 1997.

5. Schwartz A: Additional construct validity of the Schwartzcancer fatigue scale. J Nurs Meas 7(1):35-45, 1999.

6. Cleeland CS, Wang XS: Measuring and understanding fatigue.Oncology 13(11A):91-97, 1999.

7. Piper BF, Dodd MJ, Ream E, et al: Improving the clinicalmeasurement of cancer treatment-related fatigue, in Better Health ThroughNursing Research: International State of the Science, p 99. Washington, DC,American Nursing Association, 1999.

8. Cimprich, B: Attention and symptom distress in women with andwithout breast cancer. Nurs Res 50(2):86-94, 2001.

9. Cella D, Davis K, Breitbart W, et al: Cancer-related fatigue:Prevalence of proposed diagnostic criteria in a United States sample of cancersurvivors. J Clin Oncol 19(14):3385-3391, 2001.

10. Dodd MJ, Miaskowski C, Paul SM: Symptom clusters and theireffect on the functional status of patients with cancer. Oncol Nurs Forum28(3):465-470, 2001.

11. Caro JJ, Salas M, Ward A, et al: Anemia as an independentprognostic factor for survival in patients with cancer. Cancer 91(12):2214-2221,2001.

12. Littlewood TJ, Bajetta E, Nortier JWR, et al: Effects ofepoetin alfa on hematologic parameters and quality of life in cancer patientsreceiving nonplatinum chemotherapy: Results of a randomized, double-blind,placebo-controlled trial. J Clin Oncol 19(110):2865-2874, 2001.

13. Sabbatini P, Cella D, Chanan-Kahn A, et al: NCCN cancer andtreatment-related anemia guideline. The Complete Library of NCCN OncologyPractice Guidelines (CD-ROM), Rockledge, Pa, NCCN, 2001. To view the most recentversion of the guideline on-line, go to http://www.nccn.org.

14. Rozans M, Dreisbach A, Lertora JJL, et al: Palliative usesof Methylphenidate in patients with cancer: A review. J Clin Oncol20(1):335-339, 2002.

15. Geinitz H, Zimmermann FB, Stoll P, et al: Fatigue, serumcytokine levels, and blood cell counts during radiotherapy of patients withbreast cancer. Int J Radiat Oncol Biol Phys 51(3):691-698, 2001.

16. Kurzrock R: The role of cytokines in cancer-related fatigue.Cancer 92(suppl 6): 1684-1688, 2001.

17. Malik UR, Makower DF, Wadler S: Interferon-mediated fatigue.Cancer 92(suppl 6):1664-1668, 2001.

18. Holland JC, Benedeth C, Breitbart WS, et al: NCCN distressmanagement guideline. The Complete Library of NCCN Oncology Practice Guidelines(CD-ROM), Rockledge, Pa, NCCN, 2001. To view the most recent version of theguideline on-line, go to http://www.nccn.org.