Support Care Cancer (2014) 22:1797–1806 DOI 10.1007/s00520-014-2139-x
ORIGINAL ARTICLE
Exercise training in patients with advanced gastrointestinal cancer undergoing palliative chemotherapy: a pilot study Wiebke Jensen & Freerk T. Baumann & Alexander Stein & Wilhelm Bloch & Carsten Bokemeyer & Maike de Wit & Karin Oechsle
Received: 17 September 2013 / Accepted: 20 January 2014 / Published online: 15 February 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract Purpose This pilot study aimed to investigate the feasibility of two different training programs in patients with advanced gastrointestinal cancer undergoing palliative chemotherapy. Potential effects of training programs on the patients’ quality of life, physical performance, physical activity in daily living, and biological parameters were exploratorily evaluated. Methods Patients were randomly assigned to a resistance (RET) and aerobic exercise training group (AET). Both underwent supervised training sessions twice a week for 12 weeks. RET was performed at 60–80 % of the onerepetition maximum and consisted of 2–3 sets of 15–25 repetitions. The AET group performed endurance training at 60– 80 % of their predetermined pulse rate (for 10 to 30 min). Results A total of 26 gastrointestinal cancer patients could be randomized. Twenty-one patients completed the 12 weeks of intervention. The median adherence rate to exercise training of all 26 patients was 65 %, while in patients who were able to complete 12 weeks, adherence was 75 %. The fatigue score of all patients decreased from 66 to 43 post-intervention. Sleeping duration increased in both groups and muscular strength increased in the RET group. A higher number of steps in daily living was associated with higher levels of W. Jensen (*) : A. Stein : C. Bokemeyer : K. Oechsle Department of Oncology/Hematology/Bone marrow Transplantation/Pneumology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany e-mail:
[email protected] F. T. Baumann : W. Bloch Department of Molecular and Cellular Sport Medicine, Institute of Cardiovascular Research and Sport Medicine German Sport University Cologne, Cologne, Germany M. de Wit Department of Internal Medicine, Hematology and Oncology, Vivantes Klinikum Neukoelln, Berlin, Germany
physical and social functioning as well as lower scores for pain and fatigue. Conclusion RET and AET are feasible in gastrointestinal cancer patients undergoing palliative chemotherapy. Both training programs seem to improve cancer-related symptoms as well as the patient’s physical activities of daily living. Keywords Gastrointestinal cancer . palliative chemotherapy . quality of life . resistance exercise training . aerobic exercise training . physical performance
Introduction Patients with advanced gastrointestinal cancer usually suffer from severe disease-related symptoms such as diarrhea, nausea, pain, fatigue, lack of energy, and sleeping disorders [1]. In addition, chemotherapy-induced side effects such as anorexia, nausea, emesis, mucositis, diarrhea, anemia, or peripheral neuropathy can restrict their quality of life and level of physical activity significantly. Consequently, patients progressively experience decreased physical functions, reduced mobility, and severe restrictions in their activities of daily living [2]. Several studies have demonstrated the association between physical activity and disease outcome and/or quality of life in gastrointestinal cancer patients. Five trials consistently demonstrated an improved cancer-specific and overall survival rate in physically more active patients with localized colorectal cancer [3–7]. A randomized trial demonstrated that higher cardiovascular fitness was associated with improved quality of life in colorectal cancer survivors [8]. Two further studies have shown beneficial effects of low and high-intensity exercise training on markers of tumor inflammation and proliferation in patients with localized colorectal cancer [9, 10]. Another study suggested that early moderate exercise
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could have an effect on in vitro natural killer cell function after curative gastrectomy [11]. Finally, a randomized study showed beneficial effects of physical activity on biomarkers responsible for the prognosis of colorectal cancer survivors [12]. While most studies have analyzed physical activity programs in patients treated in curative intention, there are only very few studies evaluating training programs during palliative chemotherapy. However, these studies suggested that patients undergoing palliative oncological treatment are willing and able to tolerate physical activity interventions [13, 14]. Small studies with heterogeneous numbers of patients revealed that physical exercise programs are feasible even in these patients and could have beneficial effects on their quality of life and symptom burden, as well as physical and psychosocial functioning [15–32]. To date, interventional studies evaluating specific training programs and their potential effects in patients undergoing palliative oncologic treatment remain rare [13–15] and specific data on patients with gastrointestinal cancers in a palliative treatment setting are scarce. The aim of this pilot study was to investigate the feasibility of two different training programs including resistance and aerobic exercise in a small cohort of patients with advanced gastrointestinal cancer undergoing palliative chemotherapy. Furthermore, the study aimed to investigate potential effects of these programs on quality of life according to EORTCQLQ-C30 as well as on the physical performance, biological parameters, and activities of daily living. These preliminary results serve to generate further hypothesis and facilitate the planning and calculation of future studies.
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Study intervention All patients were randomly assigned to one of two intervention groups: a resistance (RET) or an aerobic exercise training group (AET). The randomization aimed to assure two comparable subgroups for exploratory evaluation of the two training programs. The RET group received supervised training sessions over 45 min, including warm-up and cool-down periods, twice a week until a total of 24 sessions over a time period of 12 weeks was achieved/completed. Resistance training of large muscle groups, including the legs, arms, back, and knees, was performed after a warm-up training on a bicycle ergometer. Strength exercises were performed at 60–80 % of the onerepetition maximum (1-RM) and consisted of two to three sets of 15–25 repetitions each. Warm-up and cool-down periods contained 5 min of light aerobic exercises and stretching. The AET group received supervised sessions lasting 45 min on a bicycle ergometer twice a week for 12 weeks. Starting with 60 % of their predetermined pulse rate in week 1–4, the working load was intensified to 70–80 % in week 5– 12. The exercise duration started with 10 min in week one and was increased up to 30 min in week 12. Warm-up and cooldown periods also included 5 min of light aerobic exercises and stretching. In both groups, “Borg’s Rating of Perceived Exertion Scale” (6–20 point scale) [33] was used to quantify the patients’ “rate of perceived exertion” (RPE). Training intensity was calculated to achieve RPEs ranking between “somewhat hard” (RPE13) and “hard” (RPE15).
Outcomes measures Patients and methods Inclusion criteria In this exploratory interventional pilot trial, patients with advanced gastrointestinal cancer, including gastric, colorectal, pancreatic, and biliary tract cancer, were included. Patients aged ≥18 years with a life expectancy ≥6 months were recruited from the oncologic outpatients clinic of the University Medical Center Hamburg-Eppendorf. Study inclusion was possible at the beginning of every new palliative treatment line. This trial was approved by the local ethics committee (PV3608). All patients had to give written informed consent prior to study inclusion. Symptomatic brain metastases, uncontrolled cardiovascular diseases, higher grades of osteoporosis, peripheral arterial insufficiency, insufficiently controlled coronary heart disease, arterial hypertension, or metabolic diseases were exclusion criteria.
At baseline and after study completion, all parameters, quality of life, physical performance, daily physical activity, biologic parameter, and preference of exercise training programs as well as disease- and treatment-related parameters, were recorded. The patients' quality of life was measured with the Quality of life questionnaire version C30 of the “European Organization for Research and Treatment of Cancer” (EORTC-QLQC30-version 3) [34]. Physical performance included muscular strength and cardiorespiratory fitness. Muscular strength was measured with the “hypothetical one-repetition maximum test” (1-RM). This test is a modification of the 1RM test, where the maximum of weight lifted by a person is measured in one single repetition [35]. This is not advisable for cancer patients; thus, 15 repetitions (15-RM) were performed in order to avoid overexertion or injuries. The result was used to estimate the 1RM in order to derive training recommendations.
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Cardiorespiratory fitness was indirectly assessed by a submaximal exercise test using the modified World Health Organization (WHO) bicycle protocol. Starting at 30 W, the working load was increased every 2 min by 15 W until the pulse rate reached a frequency of 130 per minute (Physical Working Capacity PWC130). At the end of each load period, pulse rate, blood pressure, and the subjectively perceived exertion based on the numerical scale according to Borg scale were recorded. The level of daily physical activity was assessed using a “SenseWear®” wristband, a multi-sensor measuring device worn on the triceps of the right upper arm. It continuously records a stream of physiological signals to quantify physical activity, energy expenditure, and the sleep pattern during individual “free-living” conditions [36, 37]. Each patient received this wristband for 5 days measuring their daily caloric consumption. Total energy expenditure, active energy expenditure, metabolic rate at rest, metabolic equivalent, number of steps, physical activity duration, sleeping duration, and lying down were calculated. The daily level of physical activity was measured using the “Freiburger Questionnaire of Physical Activity” which is a standardized questionnaire retrospectively assessing the patients’ daily physical activities during the previous 4 weeks and calculating their metabolic equivalent [38, 39]. Laboratory analysis of peripheral venous blood parameters included blood cell counts (monocytes, granulocytes, lymphocytes, and natural killer cells), as well as parameters of chronic inflammation (C-reactive protein and interleukin 6), glucose metabolism (serum glucose and HbA1c), and lipid metabolism (cholesterol and triglyceride). At the end of the study, patients were ask to point out which kind of sportive activities they would prefer if they could choose out of yoga/relaxation therapy, gymnastics, walking, swimming, device-steered resistance training, bicycle ergometer, and jogging.
Statistical analysis Data of all patients included in the underlying pilot study entered a central EXCEL data base. All statistical analyses were conducted using SPSS software version 21. Continuous data are shown as median or average±standard deviation, and dichotomous data are shown as counts. Differences from baseline to post-interventional analysis were evaluated by using the x2 test for categorical variables and the Wilcoxon rank sum test for continuous variables. We provide descriptive data and 95 % confidence intervals for these differences. Significance tests were conducted using a significance level of p
