For Lymphoma Patients, Vigorous Exercise Found Safe, Effective During Chemotherapy

Numerous studies have shown that vigorous exercise benefits cancer patients, both physically and psychologically. A new randomized clinical trial shows now that this is also true in patients with lymphoma receiving aerobic exercise training, compared with patients receiving usual care only. What makes this study unusual is that patients in the intervention group benefited equally whether or not they were undergoing chemotherapy at the time of exercise. The entire exercise group showed an approximate 20% improvement in measurements of physical functioning as well as in quality of life. The trial, published in the September 20 issue of the Journal of Clinical Oncology (2009;27:4605-4612), was conducted at the University of Alberta between 2005 and 2008 and led by Kerry S. Courneya, PhD, Professor and the Canada Research Chair in Physical Activity and Cancer there. Lymphoma patients from the Cross Cancer Center in Edmonton were randomly assigned to usual care (62 patients) or aerobic exercise training (60 patients). The primary endpoint was patient-rated physical functioning assessed by the Trial Outcome Index-Anemia. Secondary endpoints were overall quality of life, psychosocial functioning, cardiovascular fitness, and body composition.KERRY S. COURNEYA, PhD: “In addition to the changes patients noticed in quality of life and fatigue, we were also able to show it was the changes in their objective fitness parameters that really mediated or predicted how much better they felt from the exercise intervention. The fitter they felt, the less fatigue they reported.”The authors said that to the best of their knowledge this is the first randomized controlled trial assessing exercise in lymphoma patients. After 12 weeks of aerobic exercise training on a recumbent or upright cycle ergonometer three times a week supervised by an exercise physiologist, there was a 20% improvement in peak oxygen consumption, as well as patient-reported improvements in physical functioning, happiness, and general health, and relief of depression and lymphoma symptoms. Dr. Courneya and his colleagues credited the improvement in peak cardiovascular capacity as key to the changes in patient-rated physical functioning. Importantly, aerobic exercise training did not interfere with chemotherapy completion rate or treatment response. At 24 weeks of follow-up after the completion of exercise training, overall quality of life was still borderline or significantly superior for exercise versus usual care, without an increased risk of disease recurrence or progression. The authors concluded that aerobic exercise training significantly improved important patient-rated outcomes and objective physical functioning in lymphoma patients without interfering with medical treatments or response. “Exercise training to improve cardiovascular fitness should be considered in the management of lymphoma patients,” the researchers concluded. Lymphoma Has Been Understudied in Terms of Exercise In an interview, Dr. Courneya explained that exercise intervention studies in lymphoma are by nature different from other cancer types. “The vast majority of exercise studies have been done in early-stage breast cancer patients with good prognosis, and there are also a growing number of studies in prostate cancer relative to androgen deprivation,” said Dr. Courneya, a kinesiologist. “Lymphoma is understudied because of the many treatments to reduce the burden of disease and the slow progress of the disease, and there are lots of psychological and functional issues about preparing a patient to be repeatedly on and off treatment, possibly for many years.” Kinesiology studies on exercise and disease in the past have focused mainly on cardiovascular disease, diabetes, and obesity, he said. “Only over the past 10 years or so have the exercise-science people become interested in the role of exercise in cancer patients and cancer survivors.” He said an improvement in fitness and increase in lean body mass, aerobic capacity, and cardiovascular fitness is a very important outcome in almost any population, and known to be a very good predictor of mortality. “We did not look at mortality in this study, but our hunch is that cardiovascular fitness is a very good predictor of mortally in this population, so there is a very good possibility of survival benefits, despite existing disease and the fact that half of the patients were on therapy at the time.”BARTON KAMEN, MD, PHD, praised the study but among his caveats were that this early work needs to be revisited in five years after patients are off therapy to assess comorbidity. “We know that in pediatric patients 25% to 50% of patients will have a medical issue later on, and in one third it will be significant to life-threatening. So if you stay healthy with the right attitude through the short term, do you also protect against late effects such as cardiac disease, pulmonary disease, and end organ disease?”Battling Fatigue Dr. Courneya said the objective measures of physical conditioning underlie the important changes in overall functioning of patients. “In addition to the changes patients noticed in quality of life and fatigue, we were also able to show it was the changes in their objective fitness parameters that really mediated or predicted how much better they felt from the exercise intervention. The fitter they felt, the less fatigue they reported.” He called fatigue a profound and overwhelming symptom that interferes with all parts of a cancer patient's life. “If you can intervene and change fatigue, you can change a lot of aspects of the patient's life. There are no drug treatments or other interventions shown to improve fatigue, but exercise has a potentially unique role to play in management of fatigue in cancer patients—that's one of the most important findings in the literature.” Dr. Courneya noted that this was a fairly sophisticated exercise program that progressed over time and used interval training. Patients exercised at 50% to 60% of their aerobic capacity, “and then, for very short intervals, really hammered hard on the exercise bikes to maximum capacity.” Off Chemo vs On The study showed no difference in the results by treatment status. “In breast cancer [studies] we saw bigger exercise benefits if patients were off chemotherapy than on, and kind of expected the off-treatment group here also to have a little better exercise response than the chemotherapy group,” he said. “But we saw no difference— the 20% in fitness and the big gains in quality of life also happened for patients who were actually on chemotherapy at that time. That's a very exciting finding.” The study did not look at disease outcomes or the effect of exercise on the risk of relapse or mortality. “That's probably the million-dollar question: What is the role of these lifestyle factors in actually managing disease and living longer? The data suggest that big improvements in fitness are a very powerful predictor of mortality in many different diseases. “We cannot say that lymphoma patients who exercise will live longer or reduce the likelihood of relapse,” Dr. Courneya continued. “But even it if delayed or helped lymphoma patients prepare for the next round of treatment—which they know is coming a year or a few years down the road, the fitter they are, the more likely they will be able to endure successive rounds of treatment and benefit from the treatment.” He noted that studies are now under way looking at weight training in lymphoma patients, which in prostate cancer patients on anti-testosterone therapy has had notable effects. Also in breast cancer patients: Those who did weight training completed more of their therapy. And the Challenge trial just launched in Canada and Australia will study exercise training in an expected 962 colon cancer patients immediately after chemotherapy. Exercise intervention with disease outcomes is the primary endpoint. LLS Barton Kamen, MD, PhD, Executive Vice President and Chief Medical Officer of the Leukemia and Lymphoma Society, said that studies in leukemia and lymphoma patients are beginning to validate bigger studies in prostate, breast, and lung cancers showing that patients with a good quality of life do better through their chemotherapy. “I was pleased to see that what seems good in patients with the more common cancers who usually are not in the hospital that much also benefits patients with lymphoma.” He said AML remains fairly unique in terms of the amount of time of initial hospitalization. Dr. Kamen said some recent work is also showing that the body is capable of adapting and healing itself, as seen when exercise reduces levels of the pro-inflammatory cytokine interleukin-6 and raises levels of the anti-inflammatory IL-10. “And encouraging as much physical activity and normalcy as possible just makes sense, so I'm glad these papers are validating this,” he said. There are limitations to this paper, though, Dr. Kamen pointed out. Although more than 1,300 patients were screened, only 122 met the strict eligibility requirements. “So we don't know how biased that was, because many participants said they didn't want to do it, and a lot said they didn't have time. The researchers also excluded a lot of patients with preexisting illnesses such as high blood pressure, so that [those in the study] were not the sickest of the sick.” Dr. Kamen said he was delighted to see that lymphoma patients benefited equally from exercise therapy whether off or on chemotherapy, but he said studies in other cancers might not see this because of the wide age range in the Canadian study. “Patients here were age 18 and older,” he said. “You're not going to have 18- or 20-year-olds in a prostate or breast cancer group.” Dr. Kamen said this early work needs to be revisited in five years after patients are off therapy to assess comorbidity. “We know that in pediatric patients 25% to 50% of patients will have a medical issue later on, and in one third it will be a significant to life-threatening issue. So if you stay healthy with the right attitude through the short term, do you also protect against late effects such as cardiac disease, pulmonary disease, and end organ disease?” No Valet? Dr. Kerry Courneya and the rest of his Canadian team maximized patient adherence to the aerobic exercise training by incorporating behavioral support techniques, including “an attractive exercise facility, telephone follow- up after missed sessions, positive reinforcement of staff, variation in exercises, and paid parking.” “Parking can be outrageous in a major city,” he said.

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