Exercise and cancer-related fatigue: A review of current literature
Fatigue is one of if not the most common complaints of patients with cancer. It is reported to commonly increase with time of adjuvant therapy treatment. A usual response to this fatigue is decreased activity. Cancer-related fatigue is defined as a chronic form of tiredness, which is perceived by the patient as being unusual and persistent and inversely proportionate to the amount of exercise accomplished, and which is not reduced by rest. The etiology of cancer-related fatigue is unknown, but is theorized to be caused from inflammatory cytokines or tumor necrosis factor resulting in muscle wasting. In this report exercise as an intervention for cancer-related fatigue is reviewed, and recommendations for further research are made.
Treatment-related fatigue is one of the most prevalent and stressful symptom of cancer therapy.1-3 Until recently, physician advice for patients undergoing cancer treatment was to seek rest and avoid activities that were physically challenging. Over the past several decades there has been immense amount of scientific research regarding the use of exercise in the treatment of the undesirable side-effects of many chronic conditions, including chronic obstructive pulmonary disease, kidney failure, and cardiovascular disease. More recently, the use of exercise as an adjunct therapy for cancer treatment related symptoms has gained favor in oncologic rehabilitation as a promising intervention.4
The purpose of this update was to examine the current evidence that provides support for exorcise as an intervention for cancer-related fatigue (CRF) for physical therapists involved in oncologic rehabilitation. This paper focuses on evidence since 1990.
This review involves inductive analysis and organization of the literature addressing exercise and fatigue in patients with cancer. The vast majority of articles reviewed involved patients with breast cancer, and physical therapists reading this work should take note of this point when making clinical judgments based on the reported findings. All of the articles reviewed are first divided into theoretical articles, experimental studies, and research reviews. The experimental group is further divided into controlled studies with original data and descriptive studies. The sources of data included all those found from a MEDLINE and CINAHL literature search for the selected time period, using the keywords exercise, fatigue, and cancer. Due to the copious amount of recent literature on this topic, separation of the articles into the chosen categories was for the purpose of organizing the literature in a useful and manageable manner for the oncologic practitioner. It is anticipated this effort will allow the clinician to compare studies of similar design, preventing comparison of randomized clinical trials with theoretical articles.
The followingsection reviews nonexperimental articles. These articles are typically expert opinion, expressed in editorials, reviews, seminars, and adaptations from presentations which attempt to address definitions and mechanisms of cancer-related fatigue.
Nail and Winningham5 compare and contrast fatigue and weakness to establish distinction between the 2 symptoms experienced by patients with cancer. The influence of CRF on patients can have a significant impact on their quality of life by reduction of functional ability. Intervention guidelines for oncologic rehabilitation practitioners are made, with emphasis placed on early assessment of risk factors. Dalakas et al6 discuss fatigue associated with interferon-alpha therapy in patients with cancer, suggesting neuromuscular fatigue secondary to inflammatory cytokines as a potential cause. Similarly, St. Pierre et al7 propose the mediating effect of tumor necrosis factor as a potential mechanism by which muscle wasting occurs in patients with cancer, resulting in CRF. Nail, Winningham, Dalakas, and St Pierre all stress an understanding of the etiology of the condition in establishing effective intervention, and all point to exercise as a promising intervention.
Portenoy and Itri8 reviewed the possible etiologies, epidemiology, and management of CRF in developing guidelines for practitioners. The routine use of the following 3 questions is recommended in the clinic to facilitate quick CRF assessment. Are you experiencing any fatigue? How severe has it been in the last week, 0-10? How is the CRF interfering with your function? Further assessment of CRF is recommended using the multidimensional Piper Fatigue Self-Report Scale. Recommendations are made regarding pharmacotherapy modifications, and interventions for anemia, depression, and insomnia, and are presented in easy to follow algorithm. The benefits of exercise as a nonpharmacological intervention are stressed.
In a continuing education seminar for nurses, a review of self-care strategies, fatigue theories’ guiding current intervention and experimental studies evaluating interventions for CRF is given by Ream and Richardson.9 Self-care strategies are reported to be generally ineffective and based primarily on a rest and reduction of activity (passive) approach. Emphasis is placed on providing patient guidance concerning effective interventions, specifically exercise. Five theories are discussed which have historically been used to explain CRF. While they vary in sophistication, all recognize fatigue as an energy deficit to be corrected by physical and emotional symptom management, and activity enhancement balanced with rest. Four approaches from their review are identified that were shown to effectively manage CRF: exercise, attention-restoring activities, education, and psychological techniques. No methods are given for how the studies were evaluated.
Regarding the complexity of the energy deficit of CRF, Dimeo10 reports on the pathophysiology involved in the muscular energetic systems secondary to cancer and its treatment. In particular, Dimeo underscores the recent evidence that exercise reduces, and may even prevent CRF. As a matter of self-care activity regulation, Winningham11 advocates cancer patient use of a walking diary. Because the optimal exercise mode has yet to be determined, recording of frequency, duration, intensity, and monitoring of pulse rate are used to safely regulate exercise levels.
Lee12 specifically addresses the role of physical therapists in patients with breast cancer. Her intent was to provide a detailed history of interventions aimed at lymphedema resulting from mastectomy. In addition, aerobic exercise for reducing CRF is reviewed and recommended as an intervention for physical therapists to use for their oncology patients. This work is important in that it is the first such article we found to recommend exercise as an intervention for CRF with physical therapists as the target audience. Pinto and Maruyama13 discuss psychological distress, CRF, and other symptoms of breast cancer survivors, and recommend aerobic exercise to oncologic clinicians as an effective intervention. Data from the exercise literature is reviewed. Their critique of research efforts regard subjects (primarily patients with breast cancer and selection bias), study design (limited number of studies with control group, nonrandomized groups, and small sample size), and considerable variation in outcome measures, as well as considerable variation in the duration, type, frequency, and intensity of the exercise intervention given to the experimental group. Both Lee and Pinto and Maruyama point to moderate intensity exercise, aerobic in nature as means for reducing CRF.
As a result of the Oncology Nursing Society State-of-the-Knowledge Conference on Fatigue, Winningham et al14 report on the current understanding of CRF in 1992. Citing previous research, exercise is advocated as an intervention having a positive effect on CRF. Patients with a specific neuroimiscular impairment are recommended to receive referral to physical therapy. Winningham15 stressed the importance of structured, individualized exercise programs based on the patient’s current status, exercise type, frequency, duration, and intensity. She advocates aerobic interval training, alternating workloads between high and low sessions, as the most efficacious methods to improve physical performance in patients with cancer.
Mock et al16 present the National Comprehensive Cancer Network – Fatigue Practice Guidelines, and give an algorithm for evaluation and treatment of patients with CRF. Patient examination includes 5 factors associated with CRF: pain, emotional distress, sleep disturbance, anemia, and hypothyroidism. Effective symptom management is directed at identifying the etiology of the condition. The authors recommend the use of a moderate intensity exercise program for the improvement of functional capacity and activity tolerance. Batty and Thune17 discuss the reduction of CRF by exercise, as well as boosting immune function and potentially reducing recurrence. Additionally they recognize the optimal mode, intensity, duration, and frequency of physical activity for maximizing its therapeutic effect have yet to be determined. Dimeo4 makes similar observations regarding the effect of exercise on CRF, psychological distress symptoms, and enhancement of immune function. While Batty and Thune point out that the optimal parameters of exercise have yet to be determined, Durstine et al18 recommend that the patient with breast cancer or other chronic disease should receive a tailored exercise program based on their individual needs and clinical status. Similarly, Watson19 recommended exercise programs be low to moderate intensity, progressive, aerobic in nature and based on the individual’s level of cardiovascular conditioning.
Portenoy20 briefly discusses the scope of CRF as a complex symptom, noting that it is unusual for physicians and patients with cancer to discuss the problem, let alone specific solutions. To offer hope for patients with CRF, he draws a comparison to the history of cancer related pain and its emergence as an accepted symptom. Mock21 reviews the National Comprehensive Cancer Network Fatigue Practice Guidelines. The guidelines are presented in an easy to follow algorithm, from patient screening to primary evaluation to interventions. Primary evaluation identification of the cause of moderate to severe fatigue emphasis is placed on the 5 primary factors as reported by Mock et al16 (pain, emotional distress, sleep disturbance, anemia, and hypothyroidism). If no cause is identified a more comprehensive assessment is performed. An individualized exercise program is stressed as the nonpharmacological intervention with the strongest supporting evidence for efficacy. Additionally, education and counseling are recommended. The complexity of CRF, and gaps in the knowledge of CRF etiology are given as reason for stimulating further research in this area. Identification and correction of known causes of fatigue as the first step in management also is advocated by Curt.22
According to Mock,23 occupational difficulties experienced by patients with breast cancer returning to work with CRF is a concern that has received little recognition. Given the prevalence and impact of CRF, the Family Medical Leave Act which provides time off from work, is recommended for patients to receive intervention for breast cancer. Recommendations are made for occupational rehabilitation practitioners to help manage CRF through energy conservation and restoration activities.
Interestingly, it wasn’t until very recently that the National Cancer Institutes’ (NCI) self-care booklet24 for patients undergoing chemotherapy were advised to apply light exercise to manage CRF. Earlier versions25 of the same booklet make no mention of the use of exercise as an adjunct therapy for CRF, however mild exercise was recommended for dealing with constipation. This signals a significant acceptance by oncologic professionals for the use of exercise to ameliorate fatigue.
Of the 22 articles reviewed, 21 express a positive opinion regarding the benefits of exercise on ameliorating CRF, with the exception being the earlier versions25 of the NCI self-care booklet. Lack of consensus regarding the optimal or standardized mode of exercise is a common criticism.
The following section reviews experimental articles that were designed to describe the characteristics of CRF, typically in patients with breast cancer. Also contained are pre- or quasi-experimental reports where subjects were not randomly assigned or where control groups were not used.
Richardson and Ream26 surveyed patient’s perceptions concerning the nature, pattern, and causes of CRF in relation to their chemotherapy treatment using a symptom diary and interviews. They found that CRF was present in nearly 90% of cases. The subjects regarded fatigue to be not the same as tiredness, believed their CRF to be due to a mix of factors, most commonly their chemotherapy and sleep disturbances. Holley27 sampled 17 patients with cancer to understand the differences between cancer-related fatigue and typical fatigue and to describe its impact on their lives. She found CRF has a more rapid onset than typical fatigue, and is not the same as tiredness, having both physical and mental sensations, including an impact on patient’s perceived control over their own lives. Similar findings on the uniqueness of CRF as being different than typical fatigue are reported by Ream and Richardson,28 where they describe both the physical and mental sensations in patients with cancer and chronic obstructive airway disease. Again using a daily diary with visual analog scales, Richardson et al29 examined the onset, duration, intensity, and distress of fatigue patients receiving chemotherapy. Fatigue was measured on 4 dimensions-its extent, distress caused by it, and the disruption of social activities and work activities. Eighty-nine percent of patients reported CRF at some point during chemotherapy. They were able to establish that while CRF varies throughout the day, it is most frequently reported in the afternoon and early evening. These findings were supported by Miaskoski and Lee,30 who examined pain, sleep disturbances, and CRF over a 48-hour period in patients with cancer receiving radiation therapy. They found that patients’ pain didn’t vary significantly during the test period. However patients experienced significant sleep disturbances, and reported CRF significantly less in the morning compared to the evening.
Curt et al31 conducted telephone interviews on a sample of 379 patients with cancer who previously had received chemotherapy treatment to determine the prevalence and duration of CRF. Results indicated 76% of subjects had CRF regularly, and 30% reported having fatigue symptoms daily. Subjects were questioned about the impact CRF had on their lives. Of those having fatigue, 91% reported the symptoms prevented a normal life, and 88% reported a change in daily routine due to CRF. While 60% of subjects reported receiving physician recommendations for treating CRF, the most frequent recommendation was bed rest/relaxation. Comparable findings were reported by Stone et al32 who examined patients with cancer perception of causes, management, and impact of CRF. Fifty-eight percent of patients indicated CRF affected their lives considerably, compared to just 22% for pain and 18% for nausea/vomiting. It is noteworthy that while half of patients with CRF did not report it to their physician, only 14% with fatigue received treatment or advice from their physician. Additionally, Vogelzang et al33 separately surveyed a random sample of patients with cancer and oncologists. Fatigue was reported as affecting patients’ lives more than pain (61% compared to 19%), however oncologists treated pain more than fatigue (94% compared to 5%). Dow et al34 surveyed patients on their physical, psychological, social, and spiritual well-being to describe the long-term changes in quality of life for breast cancer survivors. Fatigue, discomfort, and difficulty sleeping were reported to be persistent after completion of their cancer treatment. The findings from these studies clearly recognize fatigue as a problem, clinically under-reported and under identified, affecting patients with cancer more of the time than any other treatment related symptom.
Greenberg et al35 examined the effect of radiation treatment on patients with breast cancer and found the fatigue response to conform to the individual’s adaptation to the physiologic stress. Fatigue increased the first week of radiation treatment, dropped the second week, and rose again the third week, reaching a plateau during the fourth week. This diminishes the view that fatigue increases linearly with cumulative radiation dose over time. Graydon et al36 interviewed patients with cancer at either the start or mid-cycle of chemotherapy treatment (n=45), or at the beginning and end of radiation therapy (n=54) to determine the most effective strategy for reducing CRF. Cancer-related fatigue was found to be greatest at mid-point in the cycle of chemotherapy, and for radiation therapy subjects it was greatest at the end of the second course of radiation therapy. The CRF relieving strategies were most effective at times of greatest fatigue. During low intensity CRF, symptom amelioration was noted to be limited. Sleep and exercise were found to be the most effective strategies used by subjects to relieve fatigue symptoms, with sleep being the most frequently employed effective strategy. However, they found overall the most frequent strategies used by subjects in attempting to ameliorate CRF was resting or reducing their level of physical activity. While the ‘common sense’ strategy of becoming sedentary was popular, patients had less energy for activity. Similar to Graydon’s finding regarding a range of effectiveness of exercise on CRF intensity (more effective no higher intensity symptoms), Porock et al,37 in a pilot study testing the effects of a 4 week exercise program on CRF in patients with advanced cancer, also found exercise effective in decreasing CRF, especially those subjects whose initial CRF levels were highest. Richardson and Ream38 studied strategies used by patients to reduce CRF by collecting data taken from structured diaries completed during chemotherapy. They found that the often-employed ‘common sense’ strategies of rest and activity modification were ineffective interventions for CRF and can in fact have paradoxical results.
Using wrist actigraphs (physical activity monitor) on patients with breast cancer receiving chemotherapy, the inverse relationship between physical activity and fatigue was demonstrated by Berger,39 Berger and Farr,40 and Berger and Higginbotham.41 Berger studied women (n=72), who were receiving chemotherapy after surgery for stage I or II breast cancer. Wrist actigraphs were used to measure activity and rest cycles for 96 hours at each treatment and for 72 hours at each cycle midpoint. A ‘roller coaster’ pattern of fatigue, inversely related to activity level is described. Also using wrist actigraphs were used to measure activity and rest cycles for 96 hours at each treatment and for 72 hours at each cycle midpoint on 72 women who were receiving chemotherapy after surgery for stage I or II breast cancer, Berger and Farr reported subjects who were less active and had increased night awakenings and subsequently higher CRF levels. Later, Berger and Higginbotham studied women (n=14) with stage I or II breast cancer receiving 4 cycles of chemotherapy using wrist actigraphs and sleep diaries. Variables representing disturbed sleep were associations with CRF. Similarly Sarna and Conde42 also found that as physical activity increased, CRF decreased using wrist actigraphs on patients with breast cancer (n=7) undergoing radiation therapy. Wrist actigraphs measured physical activity for 72 hours during the second and fifth weeks of therapy.
Self-care patterns appear different for patients who identify themselves as athletic. Schwartz43 surveyed cancer survivors responding from sports magazines regarding their physical activity patterns, and the effect of CRF on their exercise activity and ability. Survey questions focused on the amount of exercise during and after cancer treatment, symptoms experienced during training, CRF patterns, and intensity, and self-care interventions used. Sixty-nine percent of respondents reported CRF during cancer treatment. Cancer-related fatigue was least noted in the morning hours. The majority of subjects with CRF decreased their usual exercise intensity or duration levels, however exercise was the most common self-care intervention for CRF.
Dimeo, Rumberger, and Keul44 also examined cancer survivors’ (n=5) response to a 6-week aerobic exercise program and found patients experienced a clear reduction of fatigue and could carry out normal daily activities again which had been limited prior to entry into the program. The training program consisted of walking daily on a treadmill with an intensity corresponding to a lactate concentration of 3 + or – 0.5 mmol/L. By monitoring this metabolic variable, in addition to heart rate, they conclude that an aerobic exercise program of precisely defined intensity, duration, and frequency can be prescribed as therapy for primary fatigue in patients with cancer.
Of the 19 articles reviewed, all express a positive opinion regarding the benefits of exercise on ameliorating CRF. Dimeo, Rumberger, and Keul’s44 work is promising in regards to identification of optimal exercise parameters for the individual. Sleep was noted by Graydon et al36 as being reported more frequently than exercise as an effective intervention for CRF. However, several studies reviewed alert the practitioner that patients with CRF have disturbed sleep. More frequent sleep disturbances were associated with low activity levels and with increased CRF. Physical therapists should consider that exercise might also be a means to improving their patient’s sleep patterns, which would in turn reinforce the direct benefit of the increased activity reducing CRF. Use of a sleep diary is recommended for patients, to allow the physical therapist to monitor the interaction between sleep, activity, and CRF.
The following section reviews experimental studies that were designed to test the independent variables and randomly assign the subjects to groups, as well as employing a control group in the investigation.
The effects of exercise on fatigue in patients with cancer, both in treatment and survivors, are summarized in Table 1. Using a randomized clinical trial model, Mock et al45 examined the effects of a comprehensive program on the biopsychosocial adaptation of patients with breast cancer receiving adjuvant chemotherapy. The control group received standard care (which did not include a structure exercise program or support group), while the experimental group (n=9) received a rehabilitation program consisting of a walking exercise program and a support group directed by an oncology clinical nurse specialist. The rehabilitation program initiated when subjects started their chemotherapy and lasted throughout the treatment protocol (4 to 6 months). The walking program is described as a progressive, 4 to 5 times per week brisk walk of up to 45 minutes with a 5-minute cool-down. The experimental group improved in walking ability measures, had decreased psychological distress, and less fatigue in comparison to the controls. Limitations of this study were small sample size and inclusion of exercise and support group interventions to the experimental group, leaving it unclear as to which intervention was responsible for the outcomes.
Mock et al46 compared patients with breast cancer taking part in a 6-week walking exercise program with a group of patients with breast cancer receiving usual care to determine the effect of exercise on physical functioning and symptom intensity. Usual care subjects received health care in an outpatient department and were encouraged to remain active during treatment. Subjects were all Stage I or II breast cancer, were sampled at the beginning of a 6-week radiation therapy program and were randomly placed into either the control (usual care) group or the experimental (exercise) group. The exercise group was given an exercise prescription of low to moderate intensity exercise (60 to 80% of maximum heart rate) and used the Borg Scale for perceived exertion (11-13 target rating). Subjects from both groups were tested with the 12-minute Walking Test. Fatigue was the most prevalent and distressing symptom reported. The exercise group performed significantly better than the usual care group on physical functioning, fatigue, anxiety, and difficulty sleeping. They recommended exercise be prescribed and monitored for patients with breast cancer undergoing radiation therapy as a low-cost self-care activity in order to reduce fatigue and improve physical functioning.
Mock et al47,48 used a similar study method in a pilot study (50 subjects) to test the feasibility of exercise as intervention for CRF in a multi-institutional setting. Patients with breast cancer taking part in a walking exercise program were compared with a group of patients with breast cancer receiving usual care to determine the effect of exercise on fatigue, physical functioning, emotional distress, and quality of life. Subjects were receiving either chemotherapy or radiation therapy and were randomly assigned to either the control (usual care) group or the experimental (exercise) group. Subjects from both groups were tested with the 12-minute Walking Test, Profile of Mood States (POMS), the Piper Fatigue Scale (PFS), the Symptoms Distress Scale (SDS), and the Medical Outcome Study quality of life measure (SF-36). Because 50% of the control group was actively exercising independently during the study period and 30% of the experimental group was unable to maintain a regular exercise regimen, analysis was modified from intention-to-treat to an explanatory compliance cohort model. Comparisons were then made between low-exercise and high-exercise groups. Study findings indicate a home-based walking exercise program can decrease CRF and emotional distress, at the same time as improving physical functioning and quality of life.
Dimeo et al49 studied patients with breast cancer receiving chemotherapy and autologous peripheral blood stem cell transplantation to examine the effect of physical activity on fatigue in this group of patients. Patients participated in the 6-week exercise program after having recently completed their cancer treatments. The experimental group walked on a treadmill while the control group did not exercise. Similarly, Dimeo et al50 examined the effect of exercise on fatigue in patients with breast cancer after receiving chemotherapy and autologous peripheral stem cell transplantation during their hospital stay. The experimental group used a bed ergometer daily for 30 minutes until hospital discharge, while the control group did not exercise. Both studies found exercise to reduce CRF and improve physical performance in patients following high dose chemotherapy.
Schwartz et al51 examined the inverse relationship between exercise duration and subsequent reduction of CRF on patients with breast cancer receiving chemotherapy using an accelerometer (physical activity monitor) during an 8-week exercise program. Subjects exercised between 15 and 30 minutes, 3 to 4 days/week and kept fatigue diaries. They found CRF to be consistently reduced on the same day as exercise, with approximately a one-day carry over effect. The daily fatigue pattern and the effect of an 8-week program of exercise on CRF was studied by Schwartz52 on women receiving the first 3 cycles of chemotherapy. Women who adopted the exercise program generally had less CRF, while women who did not adopt the exercise program had more days of high fatigue and less days of low fatigue. This supported the earlier findings36,37 that exercise has its greatest effect on medium to high fatigue levels. Schwartz53 examined the relationship of exercise to fatigue and quality of life in patients with breast cancer receiving chemotherapy. Subjects were instructed in a home-based, 8-week low-to-moderate intensity exercise program to participate in during chemotherapy treatment. Results indicated those who exercised experienced an improvement in quality of life measures, surmised as mediated by the effect of exercise reducing CRF. Courneya et al54 evaluated exercise adherence in breast cancer survivors in a 12-week training program. Subjects trained twice a week with attendance monitored by the instructor. Overall adherence (subject attendance) was 66%. They report the keys to participation were physician and family encouragement. High fatigue level, no one to exercise with, and other health problems were cause for less participation in the program.
In the 10 experimental studies reviewed, across all training regimens whether inpatient or outpatient (supervised or community based), exercise was found as having a positive effect on CRF. Findings from these studies lead to the following recommendations for physical therapists:
(1) The exercise program begins when patients start their adjuvant therapy and lasts throughout the treatment.
(2) The exercise programs are low to moderate intensity (50-70% of maximum heart rate, or 11-13 Borg Scale rating for perceived exertion).
(3) The exercise programs are progressive, based on cardiovascular conditioning, building from 15 to 30 minutes, 3 to 5 days per week.
(4) The exercise programs are predominantly aerobic in nature, although interval training has been tested and found to be effective.
(5) Overall, the exercise programs should stress the importance of an exercise diary, documenting the session mode, intensity, duration, target heart rate, symptoms experienced, etc.
Research limitations were typically that subjects in the control groups lead active lifestyles and high symptom intensity prohibited exercise in the experimental groups. Additional study limitations are related to self-administered intervention and self-report of activity and outcomes.
RESEARCH REVIEW OF LITERATURE
The following section examines scientific reviews of literature. These articles typically involve systematic, comprehensive, and critical reviews of literature identified through databases via key terms.
Friendenreich and Courneya55 reviewed the literature on the association of exercise and oncologic rehabilitation and reported specifically regarding patients with breast cancer. Their qualitative review on 9 studies, while not comprehensive, discussed various methodological limitations observed. They concluded exercise resulted in a positive effect on the physiologic factors observed, specifically reduced fatigue, nausea, body composition, and enhanced functional capacity. Courneya and Friendenreich56 reviewed the literature on exercise and its effect on quality of life in patients with cancer. Using databases CancerLit, CINAHL, Heracles, Medline, PsychINFO, and SPORT Discus, they examined 24 studies between 1980 and 1997 that met their inclusion criteria (key words: cancer, rehabilitation, and physical exercise). Findings supported exercise as resulting in improvement of quality of life, again specifically reduced fatigue, nausea, and body composition.
Using Medline/Pub MED, Thune and Smeland57 reviewed 38 studies focusing on the effect of physical activity in oncologic rehabilitation. They found physical activity and exercise to improve quality of life and reduce fatigue. They note that exercise is not currently part of typical oncologic rehabilitation, however, the studies reviewed indicate it to be a capable intervention. Winningham58 similarly reviewed literature of CRF from a rehabilitation perspective. She found that CRF was pervasive into all aspects of quality of life regardless of stage of disease, age, or treatment regimen. Use of exercise as an effective intervention is discussed, in addition to sleep, diet, and cognitive and pharmacological therapies. Using Medline/Pub MED, Scalzitti and Sternisha59 reviewed 4 of 8 references identified with key words exercise AND (stem cell transplantation OR bone marrow transplantation) human. Their review was neither comprehensive nor critical, but was used to make clinical case decisions based on current evidence in the literature. Majid and McCarthy60 reviewed studies concentrating on the association of exercise to CRF and muscle wasting. Cancer-induced skeletal muscle wasting is identified as one of the means by which CRF arises. However, a link between amelioration of CRF and inhibition of skeletal muscle wasting using exercise has been established. Reduction of CRF by exercise is discussed.
SUMMARY AND RECOMMENDATIONS FOR FUTURE RESEARCH
Much progress has occurred in the science of cancer-related fatigue since 1990. Most of this work has been theoretical or descriptive but a growing body of reports has focused on testing interventions. Behavioral interventions to manage the symptom have predominated, with exercise as the most widely tested intervention.
The populations studied have been primarily patients with breast cancer and samples have been limited in regard to ethnicity, socioeconomic status, age, and gender. Little research has focused on exercise for fatigue management in palliative care. Research designs have been limited by small sample sizes and lack of control groups as well as other forms of methodologie rigor. There is a need to report and control variations in type and intensity of chemotherapy or other cancer treatments that are concurrent with exercise interventions.
Based on these and other identified gaps in current knowledge of exercise interventions for CRF, the following recommendations are suggested for future research in the field:
(1) Additional investigations of exercise are needed at all levels but especially at the intervention-testing level.
(2) Use of more rigorous research designs with larger sample sizes, control groups including healthy controls and attentional controls as appropriate, greater standardization of interventions to facilitate replication and increase internal validity.
(3) Use of more objective instruments and outcomes to increase validity and reliability, eg, use of instruments such as accelerometers and actigraphy to measure dose of exercise in home-based programs.
(4) Targeting of more diverse populations of patients with cancer and selection of diverse samples, especially in regard to ethnicity, socioeconomic status, age, and type of cancer diagnosis.
(5) Exploration of exercise modifications in recurrent disease and palliative care.
(6) Testing of exercise interventions across types of cancer treatments, including chemotherapy, radiation therapy, biotherapy, hormonal therapy, and surgery.
(7) More comprehensive reporting of study results in regard to refusals, withdrawals, adherence rates, and adverse events.
(8) Comparison of outcomes for supervised laboratory interventions and home-based exercise programs.
(9) Investigation of secondary outcomes of exercise interventions such as quality of life, immune function, and survival.
The recent body of literature regarding the use of exercise as an adjunct therapy for CRF has established a strong foundation for the oncologic rehabilitation team. Specifically, in all studies tested, across all training regimens, exercise was found as demonstrating effectiveness in reducing CRF.
Identified as remarkably underutilized, exercise is one of the few interventions suggested to diminish CRF and other psychosocial symptoms. From this review of literature it is evident that exercise is the treatment of choice for amelioration of CRF. This should underscore the need for physical therapists’ involvement in the oncologic patient’s rehabilitation.
Since the majority of studies described here involved patients with breast cancer, excepting Dimeo’s work with hematologic oncology patients, it is unknown how exercise would affect patients with other forms of neoplasms, such as brain tumors, lymphomas, and sarcomas. Clinicians should therefore use caution when recommending community based exercise programs for these conditions. We recommend any exercise to be done by those with advanced or recurrent disease to be done under the direct supervision of the physical therapist.
1. Dean GE, Spears L, Ferrell BR, et al. Fatigue in patients with cancer receiving interferon alpha. Cancer Pract. 1995; 3:164-172.
2. Irvine D, Vincent L, Graydon JE, et al. The prevalence and correlates of fatigue in patients receiving treatment with chemotherapy and radiotherapy. A comparison with the fatigue experienced by healthy individuals. Cancer Nurs. 1994;17:367-378.
3. 1Longman AJ Braden CJ, Mishel MH. Side effects burden in women with breast cancer. Cancer Pract. 1996;4:274-280.
4. Dimeo F. Exercise for cancer patients: A new challenge in sports medicine. Br J Sports Med. 2000;34:160-161.
5. Nail LM, Winningham ML. Fatigue and weakness in cancer patients: The symptoms experience. Semin Oncol Nurs. 1995;11:272-278.
6. Dalakas MC, Mock V, Hawkins MJ. Fatigue: Definitions, mechanisms, and paradigms for study. Semin Oncol. 1998;25:48-53.
7. St Pierre BA, Kasper CE, Lindsey AM. Fatigue mechanisms in patients with cancer: Effects of tumor necrosis factor and exercise on skeletal muscle. Oncol Nurs Forum. 1992;19:419-425.
8. Portenoy RK, Itri LM. Cancer-related fatigue: Guidelines for evaluation and management. Oncologist. 1999;4:1-10.
9. Ream E, Richardson A. From theory to practice: Designing interventions to reduce fatigue in patients with cancer. Oncol Nurs Forum. 1999;26:1295-1303; quiz 1304-1305.
10. Dimeo FC. Effects of exercise on cancer-related fatigue. Cancer. 2001;92:1689-1693.
11. Winningham ML. Walking program for people with cancer. Getting started. Cancer Nurs. 1991;14:270-276.
12. Lee M. Oncologic rehabilitation – the role of physiotherapy. Physiotherapy Singapore. 1999;2:110-112.
13. Pinto BM, Maruyama NC. Exercise in the rehabilitation of breast cancer survivors. Psychooncology. 1999;8:191-206.
14. Winningham ML, Nail LM, Burke MB, et al. Fatigue and the cancer experience: The state of the knowledge. Oncol Nurs Forum. 1991;21:23-36.
15. Winningham ML. Reader clarifies concepts of structured exercise programs in managing fatigue. Oncol Nurs Forum. 2000;27:425-426.
16. Mock V, Atkinson A, Barsevick A, et al. NCCN practice guidelines for cancer-related fatigue. Oncology. 2000;14: 151-161.
17. Batty D, Thune I. Does physical activity prevent cancer? Evidence suggests protection against colon cancer and probably breast cancer. BMJ (Clinical Research Ed.). 2000;321:1424-1425.
18. Durstine JL, Painter P, Franklin BA, et al. Physical activity for the chronically ill and disabled. Sports Med. 2000; 30:207-219.
19. Watson T. Cancer-related fatigue and the need for regular exercise. Rehabil Oncol. 2002;20:15-17.
20. Portenoy RK. Cancer-related fatigue: An immense problem. Oncologist. 2000;5:350-352.
21. Mock V. Fatigue management. Cancer. 2001;92:1699-1707.
22. Curl GA, Breitbart W, Cella D, et al. Fatigue in cancer. BMJ. 2001;322:1560.
23. Mock V. Breast cancer and fatigue: Issues for the workplace. AAOHN J. 1998;46:425-431; quiz 432-423.
24. National Cancer Institute (U.S.). Chemotherapy and You: A Guide to Self-help During Cancer Treatment. Rev. June 1999. Bethesda, Md.: National Cancer Institute; 1999.
25. National Cancer Institute (U.S.). Chemotherapy and You : A Guide to Self-help During Treatment. Rev July 1993, ed. NIH Publication No. 97-1136. Bethesda, Md (31 Center Dr., Bethesda 20892-2580): National Institutes of Health National Cancer Institute; 1997.
26. Richardson A, Ream E. The experience of fatigue and other symptoms in patients receiving chemotherapy. Eur J Cancer Care. 1996;5:24-30.
27. Holley S. Cancer-related fatigue. Suffering a different fatigue. Cancer Pract. 2000;8:87-95.
28. Ream E, Richardson A. Fatigue in patients with cancer and chronic obstructive airways disease: A phenomenological enquiry. Int J Nurs Studies. 1997;34:44-53.
29. Richardson A, Ream E, Wilson-Barnett J. Fatigue in patients receiving chemotherapy: Patterns of change. Cancer Nurs. 1998;21:17-30.
30. Miaskowski C, Lee KA. Pain, fatigue, and sleep disturbances in oncology outpatients receiving radiation therapy for bone metastasis: A pilot study. J. Pain Symptom Manage. 1999;17:320-332.
3. 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;5:353-360.
32. Stone P, Richardson A, Ream E, et al. Cancer-related fatigue: Inevitable, unimportant and unbeatable? Results of a multi-centre patient survey. Cancer fatigue forum. Ann Oncol. 2000;11:971-975.
33. Vogelzang NJ, Breitbart W, Cella D, et al. Patient, caregiver, and oncologist perceptions of cancer-related fatigue: Results of a tripart assessment survey. The Fatigue Coalition. Semin Hematol. 1997;34:4-12.
34. Dow KH, Ferrell BR, Leigh S, et al. An evaluation of the quality of life among long-term survivors of breast cancer. Breast Cancer Res Treatment. 1996;39:261 -273.
35. Greenberg DB, Sawicka J, Eisenthal S, Ross D. Fatigue syndrome due to localized radiation. J Pain Symptom Manage. 1992;7:38-45.
36. Graydon JE, Bubela N, Irvine D, Vincent L. Fatigue-reducing strategies used by patients receiving treatment for cancer. Cancer Nurs. 1995;18:23-28.
37. Porock D, Kristjanson LJ, Tinnelly K, et al. An exercise intervention for advanced cancer patients experiencing fatigue: A pilot study. J Palliative Care. 2000;16:30-36.
38. Richardson A, Ream EK. Self-care behaviours initiated by chemotherapy patients in response to fatigue. Int J Nurs Studies. 1997;34:35-43.
39. Berger AM. Patterns of fatigue and activity and rest during adjuvant breast cancer chemotherapy. Oncol Nurs Forum. 1998;25:51-62.
40. Berger AM, Farr L. The influence of daytime inactivity and nighttime restlessness on cancer-related fatigue. Oncol Nurs Forum. 1999;26:1663-1671.
41. Berger AM, Higginbotham P. Correlates of fatigue during and following adjuvant breast cancer chemotherapy: A pilot study. Oncol Nurs Forum. 2000;27:1443-1448.
42. Sarna L, Conde F. Physical activity and fatigue during radiation therapy: A pilot study using actigraph monitors. Oncol Nurs Forum. 2001;28:1043-1046.
43. Schwartz AL. Patterns of exercise and fatigue in physically active cancer survivors. Oncol Nurs Forum. 1998;25:485-491.
44. Dimeo F, Rumberger BG, Keul J. Aerobic exercise as therapy for cancer fatigue. Med Sci Sports Exerc. 1998;30:475-478.
45. Mock V, Burke MB, Sheehan P, et al. A nursing rehabilitation program for women with breast cancer receiving adjuvant chemotherapy. Oncol Nurs Forum. 1994;21:899-907; discussion 908.
46. Mock V, Dow KH, Meares CJ, et al. Effects of exercise on fatigue, physical functioning, and emotional distress during radiation therapy for breast cancer. Oncol Nurs Forum. 1997;24:991-1000.
47. Mock V, Pickett M, Ropka ME, et al. Fatigue and quality of life outcomes of exercise during cancer treatment. Cancer Pract. 2001;9:119-127.
48. Mock V, Ropka ME, Rhodes VA, et al. Establishing mechanisms to conduct multi-institutional research-fatigue in patients with cancer: An exercise intervention. Oncol Nurs Forum. 1998;25:1391-1397.
49. Dimeo FC, Tilmann MH, Bertz H, et al. Aerobic exercise in the rehabilitation of cancer patients after high dose chemotherapy and autologous peripheral stem cell transplantation. Cancer. 1997;79:1717-1722.
50. Dimeo FC, Stieglitz RD, Novelli-Fischer U, et al. Effects of physical activity on the fatigue and psychologic status of cancer patients during chemotherapy. Cancer. 1999;85: 2273-2277.
51. 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.
52. Schwartz AL. Daily fatigue patterns and effect of exercise in women with breast cancer. Cancer Pract. 2000;8:16-24.
53. Schwartz AL. Fatigue mediates the effects of exercise on quality of life. Quality Life Res. 1999;8:529-538.
54. Courneya KS, Blanchard CM, Laing DM. Exercise adherence in breast cancer survivors training for a dragon boat race competition: A preliminary investigation. Psychooncology. 2001;10:444-452.
55. Friendenreich CM, Courneya KS. Exercise as rehabilitation for cancer patients. Clin J Sports Med. 1996;6:237-244.
56. Courneya KS, Friedenreich CM. Physical exercise and quality of life following cancer diagnosis: A literature review. Ann Behav Med. 1999;21:171-179.
57. Thune I, Smeland S. [is physical activity important in treatment and rehabilitation of cancer patients?]. Tidssk Nor Laegeforen. 2000; 120:3302-3304.
58. Winningham ML. Strategies for managing cancer-related fatigue syndrome: A rehabilitation approach. Cancer. 2001;92:988-997.
59. Scalzitti DA, Sternisha C. Clinical question: Does exercise during hospitalization after stem cell transplantation decrease reports of fatigue and reduce the duration of the hospital stay? Phys Ther. 2002;82:716-721.
60. al Majid S, McCarthy DO. Cancer-induced fatigue and skeletal muscle wasting: The role of exercise. Biol Res Nurs. 2001;2:186-197.
Todd Watson, PT, DPT, OCS, FAAOMPT
Assistant Professor, Department of Physical Therapy Western Carolina University
Post-doctoral Research Fellow, Johns Hopkins University School of Nursing Victoria Mock, DNSc
Associate Professor, Johns Hopkins University School of Nursing
Director of Oncology Nursing Research, Johns Hopkins Cancer Center
Copyright Rehabilitation in Oncology 2003
Provided by ProQuest Information and Learning Company. All rights Reserved