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Journal of Pain and Symptom Management
Vol. 35 No. 5 May 2008
Original Article
Effects of a Walking Intervention on Fatigue-Related Experiences of Hospitalized Acute Myelogenous Leukemia Patients Undergoing Chemotherapy: A Randomized Controlled Trial Pi-Hua Chang, MSN, Yeur-Hur Lai, PhD, Shiow-Ching Shun, PhD, Lih-Ying Lin, MSN, Mei-Ling Chen, PhD, Youngsen Yang, MD, Jen-Chen Tsai, DSN, Guey-Shiun Huang, PhC, and Sue-Yueh Cheng, PhC Department of Nursing (P.-H.C., L.-Y.L.) and Internal Medicine Department (Y.Y.), Taichung Veterans General Hospital, Taichung; Department of Nursing (Y.-H.L., S.-C.S., G.-S.H.), College of Medicine, National Taiwan University, Taipei; Graduate Institute of Nursing, Chang-Gung University (M.-L.C.), Tau-Yuan; and School of Nursing (J.-C.T., S.-Y.C.), Taipei Medical University, Taipei, Republic of China
Abstract The purpose of this randomized, controlled clinical trial was to preliminarily examine the effects of a three-week walking exercise program (WEP) on fatigue-related experiences of acute myelogenous leukemia (AML) patients receiving chemotherapy. Eligible AML patients were randomly assigned to either an experimental group (n ¼ 11), which received 12 minutes of WEP per day, five days per week for three consecutive weeks, or to a control group (n ¼ 11), which received standard ward care. Effects of the WEP were assessed by seven indicators: worst and average fatigue intensities, fatigue interference with patients’ daily life, 12-minute walking distance, overall symptom distress, anxiety, and depressive status. All patients were evaluated four times: before chemotherapy (baseline or Day 1), Day 7, Day 14, and Day 21 of chemotherapy. Data were analyzed by Generalized Estimating Equation and revealed that AML patients in the three-week WEP group had a significantly greater increase in 12-minute walking distance than the control group. Patients in the WEP also had lower levels of fatigue intensity and interference, symptom distress, anxiety, and depressive status than the control group. Although preliminary, our results strongly suggest that three weeks of systematic walking exercise is clinically feasible for AML patients undergoing chemotherapy and can effectively improve their fatigue-related experiences. J Pain Symptom Manage 2008;35:524e534. Ó 2008 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. Key Words Fatigue, cancer, leukemia, exercise, depression, anxiety, symptom
Address correspondence to: Yeur-Hur Lai, PhD, National Taiwan University, School of Nursing, College of Medicine, #1 Jen-Ai Road Sector 1, Taipei 100, Taiwan. E-mail:
[email protected] Accepted for publication: June 29, 2007. Ó 2008 U.S. Cancer Pain Relief Committee Published by Elsevier Inc. All rights reserved.
Introduction Acute myelogenous leukemia (AML) is the major hematological malignancy in adults in Taiwan.1 The primary treatment for AML is chemotherapy,2 which has the side effect of 0885-3924/08/$esee front matter doi:10.1016/j.jpainsymman.2007.06.013
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Effects of a Walking Intervention on Fatigue-Related Experiences
fatigue, one of the most pervasive and prevalent problems faced by cancer patients receiving chemotherapy.3e5 This problem may be even more severe for AML patients because they often undergo an intensive course of chemotherapy. For example, the most common induction chemotherapy for AML patients (with cytarabine and idarubicin) is given every three weeks as a course.2,6 In addition, due to the nature of their disease, AML patients usually have anemia, which may exacerbate fatigue during chemotherapy.7 Fatigue has been reported to affect cancer patients’ quality of life,8 mood,9,10 and physical performance.9,11 Therefore, a program to ease fatigue-related experiences during chemotherapy would benefit AML patients. Exercise has been recognized as one of the most effective interventions for decreasing cancer-related fatigue.12e15 According to Winningham’s psychobiologic-entropy model,16 fatigue is an ‘‘energy deficit’’ that leads to decreased activity and secondary fatigue. It can lead to a further decline in functional status.17 Increasing physical activity may generate energy and decrease fatigue. Physical activity, such as exercise, may lead to a more positive mood,15,18,19 thus a better quality of life.19e22 Various kinds of exercise programs have been adapted for cancer patients in outpatient settings or at home, such as aerobic exercise,13,23 stationary bicycle training, and walking exercise.24,25 Most of these exercise-related clinical studies included patients with cancers of the breast, prostate, colonerectum, lung, or mixed groups of cancer patients;15,19,21,22,24e31 only a few studies have been conducted on patients with hematological malignancies.23,32e34 Walking has been found to effectively improve a person’s physical function,14,15 decrease fatigue,14,15 and improve emotional status.15,35 However, most studies on walking used a treadmill for training.13,14,36 For most hospitals, a treadmill is not standard equipment and it is not available to most hospitalized patients. In traditional Chinese culture, sick people are thought to lack energy and health is believed to be most safely preserved by rest; therefore, exercise is generally not encouraged for patients undergoing treatment. A culturally acceptable and easily applied program, such as walking, is urgently needed to decrease chemotherapy-induced fatigue for frail leukemia
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patients in Taiwan. Therefore, the aim of the current study was to develop and preliminarily examine the effects of a clinically feasible, structured three-week walking exercise program (WEP) on fatigue-related experiences of hospitalized AML patients undergoing chemotherapy.
Methods Patients and Procedures Patients were recruited from an inpatient hematology ward at a medical center in central Taiwan. Institutional Review Board evaluation and approval were obtained before conducting the study. Eligible subjects were (1) adult patients (>18 years of age) diagnosed with AML and aware of their diagnosis, (2) prescribed chemotherapy, (3) in satisfactory functional condition as determined by a score of 0e3 on the Eastern Cooperative Oncology GroupdPerformance Status (ECOG-PS) rating,37,38 and (4) willing to sign a consent form to participate. To control for heterogeneity among treatment protocols, we recruited only AML patients receiving inductive therapy using cytarabine 100 mg/m2/day by continuous IV infusion for seven days and idarubicin 12 mg/m2/day IV push on Days 1, 2, 3; and patients receiving high-dose cytarabine for 6e8 doses and idarubicine 12 mg/m2/day for three days.2 A trained, master’s-prepared nurse research assistant (RA) explained the research purpose and procedure.
Design and Interventions This preliminary clinical trial used a randomized, controlled design to examine the effects of a clinically feasible, structured WEP on patients with AML. Of 28 eligible patients approached, 24 agreed to participate and they were randomly assigned to either an experimental group that received the WEP or a control group. One patient dropped out of each group due to severe complications, leaving 11 subjects in each group (Fig. 1).
Program and Procedures Walking Exercise Program. Because we could find no standard exercise program for cancer patients undergoing chemotherapy, we developed the WEP based on principles for the frequency, duration, and intensity of activity
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Chang et al.
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Eligible subjects (n = 28)
Enrollment
Family refuse (n = 4)
Randomized (n = 24)
CG (n = 12)
Allocation
WEP (n = 12)
Severe infection (n = 1)
Follow-up
Severe bleeding (n = 1)
Completed study (n =11)
Analysis
Completed study (n = 11)
Fig. 1. Flow diagram of the WEP procedures.
suggested by the American College of Sports Medicine39 and a literature review.15,40e42 The three-week WEP consisted of 12 minutes walking in the hospital hallway on five days per week. The trained RA accompanied patients continuously to follow the protocol. Patients were encouraged to walk at a speed to reach their target heart rate (resting heart rate plus 30). To ensure patients’ safety while walking, their blood pressure, pulse rate, and respiratory rate were monitored before and during exercise by a portable heart rate and BP monitor worn on the wrist. The normal ranges used were (1) heart rate between 60 and 110 beats per minute, (2) respiratory rate 1
8 3
72.7 27.3
6 5
54.5 45.5
0.659
Performancea,b 0 >1
a
Difference between groups tested by Fisher’s Exact test. Performance ¼ performance status as determined by the ECOG-PS. c 7 þ 3: patients received cytarabine for seven days and idarubicin for three days. d HDAC (high-dose cytarabine): patients received idarubicin for three days and high-dose cytarabine every 12 hours, total 6e8 doses. b
intensity (z ¼ 2.50) (Table 3). The patterns of change in the two kinds of fatigue intensity show that patients in the WEP group remained at a constant level of fatigue across the three weeks, but for patients in the control group, fatigue intensities significantly increased across the three weeks except for average fatigue intensity in the third week (Fig. 2a,b).
Fatigue Interference At baseline, fatigue interference was not significantly different between the two groups (Table 3). However, GEE analysis revealed three significant time-dependent changes in
fatigue interference, indicating an overall tendency for fatigue interference in the control group to increase over time relative to baseline (z ¼ 3.26, 3.30, 2.39, respectively). However, the timeegroup interactions demonstrated significant differences across time between the two groups from the end of first week to the end of the third week (z ¼ 2.03, 2.04, 2.28, respectively) (Table 3). The patterns of change for fatigue interference show that it was relatively constant across the three weeks for patients in the WEP group, but increased significantly for the control group from Days 7 to 21 (Fig. 2c).
Table 2 Time Course of Effects of Walking Exercise Program on Subjects (n ¼ 22) Variable
Group
Fatigue (average)
EG CG EG CG EG CG EG CG EG CG EG CG EG CG
Fatigue (worst) Fatigue interference 12-minute walking distance (m) Symptom distress Anxiety Depressive status
Day 1
Day 7
Day 14
Day 21
M SD
M SD
M SD
M SD
4.4 3.6 2.1 3.0 5.8 3.8 3.0 4.1 4.0 3.2 2.4 2.7 329.1 171.2 399.3 199.4 1.78 0.55 1.41 0.34 1.83 1.08 1.36 1.21 1.85 1.10 1.36 1.27
4.1 2.3 5.5 2.4 5.6 2.7 7.5 2.4 3.6 2.5 4.6 2.2 409.6 177.8 300.7 116.7 1.56 0.38 1.91 0.46 1.30 1.23 1.77 1.23 1.42 0.80 1.95 0.76
4.4 2.4 5.8 3.1 5.6 3.1 7.1 2.7 4.3 2.8 5.6 2.7 407.2 154.5 280.3 165.7 1.85 0.71 2.02 1.05 1.15 1.15 1.48 1.39 1.23 1.01 1.59 1.54
4.6 3.0 4.8 3.5 5.7 3.8 6.3 3.8 3.5 2.4 5.2 3.3 377.2 169.7 269.4 160.4 1.65 0.45 1.98 1.00 1.15 1.27 1.68 1.65 1.25 1.22 1.47 1.51
EG ¼ experimental group (receiving Walking Exercise Program); CG ¼ control group.
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Table 3 GEE Analysis of Effects of WEP on AML Patients Receiving Chemotherapy (n ¼ 22) 95% CI Variable Average fatigue intensity
Worst fatigue intensity
Fatigue interference
12-minute walking distance
Symptom distress
Anxiety
Depressive status
Comparison
Estimate
Standard Error
Low
High
Z
P
Intercept GR(EG/CG) TM1 (D7/D1) TM2 (D14/D1) TM3 (D21/D1) GR(EG)* TM1 GR(EG)* TM2 GR(EG)* TM3 Intercept GR(EG/CG) TM1 (D7/D1) TM2 (D14/D1) TM3 (D21/D1) GR(EG)* TM1 GR(EG)* TM2 GR(EG)* TM3 Intercept GR(EG/CG) TM1 (D7/D1) TM2 (D14/D1) TM3 (D21/D1) GR(EG)* TM1 GR(EG)* TM2 GR(EG)* TM3 Intercept GR(EG/CG) TM1 (D7/D1) TM2 (D14/D1) TM3 (D21/D1) GR(EG)* TM1 GR(EG)* TM2 GR(EG)* TM3 Intercept GR(EG/CG) TM1 (D7/D1) TM2 (D14/D1) TM3 (D21/D1) GR(EG)* TM1 GR(EG)* TM2 GR(EG)* TM3 Intercept GR(EG/CG) TM1 (D7/D1) TM2 (D14/D1) TM3 (D21/D1) GR(EG)* TM1 GR(EG)* TM2 GR(EG)* TM3 Intercept GR(EG/CG) TM1 (D7/D1) TM2 (D14/D1) TM3 (D21/D1) GR(EG)* TM1 GR(EG)* TM2 GR(EG)* TM3
2.09 2.27 3.36 3.73 2.73 3.64 3.73 2.55 3.0 2.82 4.45 4.09 3.27 4.73 4.27 3.36 2.38 1.58 2.23 3.23 2.86 2.58 2.83 3.32 399.3 70.2 98.6 119.1 129.9 179.1 197.2 178.0 1.41 0.37 0.50 0.61 0.57 0.71 0.54 0.69 1.02 0.35 0.31 0.09 0.24 0.70 0.60 0.75 1.36 0.49 0.59 0.23 0.10 1.02 0.85 0.70
0.86 1.29 1.00 1.00 1.36 1.54 1.49 1.57 1.19 1.61 1.34 1.20 1.38 2.04 1.66 1.72 0.78 1.20 0.68 0.98 1.20 1.27 1.39 1.46 57.3 75.5 58.8 44.9 76.0 68.1 54.3 80.9 0.10 0.19 0.16 0.31 0.30 0.21 0.37 0.33 0.26 0.35 0.19 0.25 0.29 0.33 0.33 0.40 0.37 0.48 0.22 0.31 0.25 0.31 0.44 0.48
0.41 0.27 1.42 1.79 0.07 6.65 6.65 5.62 0.68 0.38 1.83 1.73 0.58 8.73 7.53 6.74 0.85 0.78 0.89 1.31 0.51 5.06 5.56 6.18 287.0 218.3 213.8 207.1 278.9 45.7 90.9 19.4 1.22 0.00 0.18 0.01 0.02 1.13 1.27 1.35 0.51 0.33 0.07 0.39 0.34 1.35 1.25 1.53 0.65 0.46 0.15 0.37 0.38 1.62 1.71 1.65
3.77 4.80 5.30 5.66 5.38 0.62 0.81 0.53 5.32 5.97 7.08 6.45 5.99 0.72 1.01 0.01 3.91 3.94 3.56 5.14 5.21 0.09 0.11 0.46 511.7 77.9 16.6 31.0 19.1 312.5 303.6 336.5 1.61 0.74 0.82 1.22 1.15 0.30 0.19 0.04 1.53 1.04 0.69 0.57 0.81 0.06 0.05 0.03 2.08 1.44 1.03 0.83 0.59 0.42 0.001 0.24
2.44 1.76 3.40 3.77 2.01 2.36 2.50 1.62 2.53 1.75 3.33 3.40 2.36 2.31 2.57 1.95 3.05 1.31 3.26 3.30 2.39 2.03 2.04 2.28 6.97 0.93 1.68 2.65 1.71 2.63 3.63 2.20 14.3 1.96 3.03 1.98 1.90 3.41 1.46 2.08 3.93 1.01 1.58 0.37 0.81 2.14 1.82 1.89 3.72 1.01 2.64 0.74 0.41 3.35 1.96 1.46
0.010 0.080
