Exercise Regimen Reduces Fatigue

Fatigue is one of the most common, distressing, and frustrating side effects of cancer and its treatment.[1] While red blood cell growth factors (erythropoietin) have greatly reduced the fatigue associated with anemia, patients continue to be confronted with fatigue that interferes with normal physical and emotional function both during and following treatment.

Cancer treatment-related fatigue is associated with reduced physical strength, aerobic function, cognitive dysfunction, and depressed mood.[2] Fatigue is generally reported to be worse among younger patients.[3] While some chemotherapy regimens may cause more fatigue than others, there are no identified risk factors for disabling levels of fatigue.

Patient Overview

MK is a 58-year-old woman with stage III breast cancer. She received neoadjuvant chemotherapy consisting of doxorubicin (A), cyclophosphamide (C), and paclitaxel (T), or ACT. After 6 weeks of treatment she had achieved a good tumor response (shrinking approximately 3 cm) and was a candidate for breast conservation surgery. One month following the completion of surgery she returned to continue chemotherapy and completed the dose dense ACT regimen. In order to prevent neutropenia she received granulocyte colony-stimulating factor (G-CSF, filgrastim [Neupogen]). When her hemoglobin fell below 11 g/dL she was started on an erythropoietic agent to correct her anemia.

Although from a medical perspective MK tolerated treatment well, she continued to experience worsening fatigue, complained of feeing irritable and moody, and reported problems with her memory. These side effects were sufficiently troubling that she didn't feel comfortable doing her usual activities and felt safest at home. She stopped going to the grocery store, asking her husband to help with this and other chores.

MK was assessed for depression and started on Wellbutrin XL 300 mg daily. Within 2 weeks of starting Wellbutrin XL her symptoms of depression improved. However, her fatigue persisted; during the second half of chemotherapy she became increasingly sedentary, only leaving the house for medical appointments. She would walk from her house, to the car, and then to the infusion room and be exhausted and out of breath. The more she protected herself and tried to rest the worse she felt, not only physically but emotionally. Fatigue was taking its toll on her as she became more and more debilitated from trying to reduce her fatigue by resting and doing nothing.

As MK neared the completion of chemotherapy she vocalized great concern about her ability to continue with treatment and begin radiation therapy; she was just too weak. At this point, MK was referred to the cancer rehabilitation program.

The cancer rehabilitation program required MK to commit to exercising with a therapist 3 days a week. A systematic, step-by-step approach was taken to increase her aerobic capacity and muscle strength. Each exercise session started off with a slow warmup on a recumbent bicycle and then increased in intensity to approximately 60% to 75% of her predicted maximum heart rate. She pedaled at this intensity for varying periods of timeless time when she initially stated the program, with gradual increases in duration at this constant intensity.

MK's aerobic exercise program was paced so that she had 2 weeks of pushing herself and then a week of recovery. During recovery weeks, MK's duration and intensity of aerobic exercise was reduced by approximately 25% so her body could adapt to the stresses of exercise.

Following each aerobic exercise session, MK would complete at least two different upper body exercises and two lower body resistance exercises. These exercises were usually completed on a weight machine, but she was also taught how to do these exercises with Thera-Bands, which are rubber bands of varying thickness and resistance. Initially, MK completed 1 set of 8 repetitions and worked up to doing 2 sets of 10 repetitions before moving up to a heavier weight or Thera-Bands with greater resistance.

MK began radiation during the third week of the exercise program. She continued to complain of fatigue but was able to walk into the clinic without becoming exhausted and was starting to be able to do more of her usual activities. She reported that although she was still overwhelmed at times by her fatigue, overall her mood and general outlook on life was better. She was starting to "feel like a survivor" and as though she could make it through the full course of radiation therapy.

MK continued to attend the complete 8-week cancer rehabilitation program and then entered phase 2 of the program: transition to home-based exercise. During the transition period, the therapist spent time teaching MK how to execute the strength-training exercises at home with the Thera-Bands. The aerobic exercise program was also reviewed. She continued to exercise with her therapist 1 day a week for 4 weeks, and then was on her own with weekly or biweekly telephone calls to help her stay with the program.[4]

After 6 weeks of exercise at home, MK started to slide and was not completing the target exercise prescription. She returned to the supervised setting and realized that having someone to exercise with and report to was what she needed to follow the program. Through the cancer rehabilitation program, MK was introduced to another survivor who lived in her area and the two began exercising together on a regular basis.

Outcome

Over the course of 16 weeks, MK increased her aerobic capacity by 32% and her muscle strength by 19%. She resumed all of her normal activities and reported feeling better than she felt before breast cancer. Her new-found strength and fitness had resolved the fatigue problems associated with disuse and debilitation. The
prompt use of G-CSF prevented neutropenia and associated complications, and the erythropoietic agent corrected her anemia. The use of Wellbutrin XL alleviated the mood disturbance experienced during treatment.

Discussion

The etiology of cancer-related fatigue is unknown; however, a neurophysiologic model suggests that chemotherapy and biotherapy may impair the central and peripheral nervous systems—those medications that act on the central nervous system may compound fatigue.[5] Other significant etiologies of fatigue should be considered: pain, infection, depression, sleep deprivation, anemia, nutritional status, heart failure from anthracycline therapy, hypothyroidism, cardiopulmonary insufficiency, medications, and activity level.

Fatigue assessment should ideally begin before treatment is initiated. Measuring fatigue on a 0 to 10 scale (no fatigue to the worst imaginable fatigue) is clinically feasible and relevant, and can determine clinically important differences in fatigue that might indicate when intervention is necessary.[6] Interventions that have demonstrated efficacy in reducing fatigue, when other causes have been ruled out or addressed (eg, anemia, neutropenia), include education, physical activity, energy conservation, and medications.[7-10] Ideally, a comprehensive multidisciplinary treatment approach would be used to determine the best intervention for a patient. Treatment decisions should be based on physical examination, laboratory tests, and psychosocial assessment of the individual.

In this case study, MK's fatigue persisted despite correction of anemia and initiation of an antidepressant. While her health was improved by these interventions, the cause of her ongoing fatigue appeared to be related to declines in functional ability associated with inactivity.[11,12] The progressive, individualized exercise program improved MK's functiobnal ability and muscle strength, while the medications corrected her anemia and depression.

Cancer-related fatigue is a complex and all too common side effect of treatment that needs to be assessed early. Approaches to intervention need to consider a wide variety of causes; multiple different treatment approaches may be required to maintain optimal health during treatment.

References:

1. 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 5:353-360, 2000.

2. Mock V: Fatigue management: Evidence and guidelines for practice. Cancer 92(6 suppl):1699-1707, 2001.

3. Bower JE, Ganz PA, Desmond KA, et al: Fatigue in breast cancer survivors: Occurrence, correlates, and impact on quality of life. J Clin Oncol 18:743-753, 2000.

4. Schwartz AL, Winters K: Promoting physical activity in cancer survivors, in McTiernan A (ed): Physical Activity, Energy Balance, and Cancer: Etiology and Prognosis. New York, Marcel Dekker, 2006.

5. National Comprehensive Cancer Network (Jenkinton PA): Practice guidelines for cancer-related fatigue. NCCN, 2003.

6. Schwartz AL, Meek PM, Nail LM, et al: Measurement of fatigue: Determining minimally important clinical differences. J Clin Epidemiol 55:239-245, 2002.

7. Schwartz AL, Thompson JA, Masood N: Interferon-induced fatigue in patients with melanoma: A pilot study of exercise and methylphenidate. Oncol Nurs Forum 29:E85-E90, 2002.

8. Mock V: Clinical excellence through evidence-based practice: Fatigue management as a model. Oncol Nurs Forum 30: 787-796, 2003.

9. Schwartz AL: Fatigue mediates the effects of exercise on quality of life in women with breast cancer. Qual Life Res 8:529-538, 1999.

10. Barsevick A, Dudley W, Beck S, et al: A randomized clinical trial of energy conservation for cancer-related fatigue. Cancer 100:1302-1310, 2004.

11. Winters K, Schwartz AL: Quality of life and fatigue in breast cancer, in McTiernan A (ed): Physical Activity, Energy Balance, and Cancer: Etiology and Prognosis. New York, Marcel Dekker, 2006.

12. Schwartz AL: Physical activity -after a cancer diagnosis: Psychosocial outcomes. Cancer Invest 22(1):82-92, 2004.