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Few studies have evaluated an individualized home-based exercise prescription during and after cancer treatment.The purpose of this study was to evaluate the effectiveness of a home-based exercise training intervention, the Pro-self Fatigue Control Program on the management of cancer-related fatigue.Participants (N = 119) were randomized into 1 of 3 groups: group 1 received the exercise prescription throughout the study; group 2 received their exercise prescription after completing cancer treatment; and group 3 received usual care. Patients completed the Piper Fatigue Scale, General Sleep Disturbance Scale, Center for Epidemiological Studies-Depression Scale, and Worst Pain Intensity Scale.All groups reported mild fatigue levels, sleep disturbance, and mild pain, but not depression. Using multilevel regression analysis, significant linear and quadratic trends were found for change in fatigue and pain (ie, scores increased, then decreased over time). No group differences were found in the changing scores over time. A significant quadratic effect for the trajectory of sleep disturbance was found, but no group differences were detected over time. No significant time or group effects were found for depression.Our home-based exercise intervention had no effect on fatigue or related symptoms associated with cancer treatment. The optimal timing of exercise remains to be determined.Clinicians need to be aware that some physical activity is better than none, and there is no harm in exercise as tolerated during cancer treatment. Further analysis is needed to examine the adherence to exercise. More frequent assessments of fatigue, sleep disturbance, depression, and pain may capture the effect of exercise.