Skip to main content
Download PDF
  • Study protocol
  • Open access
  • Published:

Design of the Physical exercise during Adjuvant Chemotherapy Effectiveness Study (PACES):A randomized controlled trial to evaluate effectiveness and cost-effectiveness of physical exercise in improving physical fitness and reducing fatigue

BMC Cancer volume 10, Article number: 673 (2010) Cite this article

Abstract

Background

Cancer chemotherapy is frequently associated with a decline in general physical condition, exercise tolerance, and muscle strength and with an increase in fatigue. While accumulating evidence suggests that physical activity and exercise interventions during chemotherapy treatment may contribute to maintaining cardiorespiratory fitness and strength, the results of studies conducted to date have not been consistent. Additional research is needed to determine the optimal intensity of exercise training programs in general and in particular the relative effectiveness of supervised, outpatient (hospital- or physical therapy practice-based) versus home-based programs.

Methods

This multicenter, prospective, randomized trial will evaluate the effectiveness of a low to moderate intensity, home-based, self-management physical activity program, and a high intensity, structured, supervised exercise program, in maintaining or enhancing physical fitness (cardiorespiratory fitness and muscle strength), in minimizing fatigue and in enhancing the health-related quality of life (HRQoL). Patients receiving adjuvant chemotherapy for breast or colon cancer (n = 360) are being recruited from twelve hospitals in the Netherlands, and randomly allocated to one of the two treatment groups or to a 'usual care' control group. Performance-based and self-reported outcomes are assessed at baseline, at the end of chemotherapy and at six month follow-up.

Discussion

This large, multicenter, randomized clinical trial will provide additional empirical evidence regarding the effectiveness of physical exercise during adjuvant chemotherapy in enhancing physical fitness, minimizing fatigue, and maintaining or enhancing patients' quality of life. If demonstrated to be effective, exercise intervention programs will be a welcome addition to the standard program of care offered to patients with cancer receiving chemotherapy.

Trial registration

This study is registered at the Netherlands Trial Register (NTR 2159)

Peer Review reports

Background

Treatment with chemotherapy is associated with multiple physical and psychosocial side effects, including reduced cardiorespiratory fitness and muscle strength and increased fatigue [1, 2]. Fatigue is a common problem reported by patients undergoing chemotherapy, with prevalence rates ranging from 80% to 100% [3–5]. Among breast cancer survivors, the prevalence of chronic, severe fatigue has been reported to range from 24% to 40%. Chronic fatigue has a negative impact on activities of daily life, social reintegration and overall quality of life [3]. Fatigue and muscle wasting may be directly therapy-induced, but may also be attributed in part to sedentary habits and subsequent loss of physical fitness (cardiorespiratory fitness and muscle strength) [6].

There is accumulating evidence that exercise interventions during chemotherapy may contribute to preserving cardiorespiratory fitness [7–14] and muscle strength [13, 15, 16], decreasing fatigue [13, 14, 17–19], mood disturbances [13, 14, 17, 18] and lean body mass [13], and enhancing self-reported functioning [18], overall HRQoL [13, 14, 18] and immune-function [17].

However, results of studies to date have not been entirely consistent [17, 18, 20], which may be due, in part, to methodological limitations. Most studies have employed small sample sizes (ranging from 6 to 60 patients in the intervention arm) and some have failed to include a control group. Furthermore, the interventions employed in these studies varied widely. Some studies have investigated low intensity, home-based exercise programs, while others report on intensive, structured and supervised training, with or without resistance training [14]. Most of the previous studies employed exercise programs that are less than optimal in terms of important aspects of exercise physiology [17]. It is hypothesized that an intervention that combines resistance training and aerobic exercise may be most effective [15].

Adherence to exercise interventions is a challenging task [20]. When shaping an exercise program to the needs of the individual patient, current fitness level, health beliefs and health behavior need to be taken into consideration, while still maintaining a core, standardized program that can be relatively easily implemented in a range of health care settings [20].

Effects of exercise interventions may be moderated by exercise history and health beliefs. It is likely that sociodemographic, medical variables, and patients' preferences also moderate the effects of exercise interventions during chemotherapy [21, 22].

It should be noted that most trials are characterized by low participation rates (as low as 17% of potentially eligible patients), which may limit the generalizability of the results, particularly if those included in the trial tended to be more habitually active, more highly motivated and/or better educated than the target population as a whole [13, 14].

Finally, to our knowledge, no study to date, has evaluated the cost-effectiveness of exercise interventions during chemotherapy.

In summary, while there is evidence supporting the beneficial effects of exercise programs during chemotherapy, the results across studies are not entirely consistent. Additional studies are needed to determine the optimal content, intensity, and form of exercise training programs. Specifically, there is need for research that investigates an exercise program that combines aerobic exercise and muscle strength training, as well as the relative effectiveness of supervised, outpatient versus unsupervised home-based programs. Such research should also consider the possible moderating effect of exercise history, current levels of fitness and physical activity, health attitudes, and motivation on physical exercise program effectiveness. The sample size and thus power of future trials should be sufficient to be able to demonstrate program effectiveness and cost-effectiveness based on both physiological performance measures, and fatigue.

In this article, we describe the design of a randomized, controlled, multicenter clinical trial comparing: (1) a low to moderate intensity, home-based, self-management physical activity program (Onco-Move), (2) a high intensity, structured, supervised exercise program (OnTrack) and (3) usual care control group, in patients undergoing adjuvant chemotherapy for breast or colon cancer.

We hypothesize that patients who undergo the Onco-Move or the OnTrack program will achieve better physical fitness levels, as assessed by objective performance tests, will report less fatigue, less mood disturbance, higher levels of physical activity and functioning in daily life, and better HRQoL than patients in the usual care control group. Furthermore, we hypothesize that patients in the OnTrack program will achieve more muscle strength and achieve greater gains in cardiorespiratory fitness than patients who follow the Onco-Move program. No differences are expected between the two programs in self-reported outcomes during treatment. However, it is hypothesized that, at the six month follow-up, patients who participated in the OnTrack program will report less fatigue, and higher levels of physical activity and functioning than those who participated in the Onco-Move program or usual care control group. Finally, we hypothesize that the OnTrack and Onco-Move programs will lead to a reduction in health care costs, patient and family costs, and costs of production losses, resulting in an cost-effective intervention.

If demonstrated to be effective, the availability of such physical activity and exercise intervention programs will be a welcome addition to the standard program of care offered to patients with cancer undergoing chemotherapy.

Methods

The present trial is one of four randomized controlled trials included in the Alpe d'HuZes Cancer Rehabilitation (A-CaRe) program. All studies within the A-CaRe program will evaluate the effectiveness and the cost-effectiveness of exercise-based rehabilitation interventions in different cancer patient and survivor groups. In the PACES study, patients are being randomized to one of three study arms. They will participate either in the Onco-Move or the OnTrack program, or will undergo usual care. The design of the trial and the anticipated flow of the participants are displayed graphically in Figure 1. The trial has been approved by the institutional review board of the Netherlands Cancer Institute (under number PTC 09.2711), as well as by the review boards of all hospitals from which patients are being recruited. This protocol follows the CONSORT guidelines [23]. Patient recruitment and data collection for this trial started in April, 2010.

Figure 1
figure 1

Overview of study procedures.

Full size image

Study sample

The study sample will be composed of patients with histologically confirmed primary breast or colon cancer who are scheduled to undergo adjuvant chemotherapy. There is no upper age limit for study participation.

Potentially eligible patients are screened for the presence of comorbid conditions that would contraindicate participation in a physical activity/exercise program. This includes patients with serious orthopedic conditions that would hamper functional recovery, and patients with serious cardiovascular or cardiopulmonary conditions (or risks) who would not be able to train at the intensity level required. Patients suffering from malnutrition as evidenced by a BMI < 18 kg/m2, unintended weight loss of more than 5% per month, or more than 10% unintended weight loss during the previous six month period are considered poor candidates for physical condition training and thus are not eligible for participation. Patients judged to have serious psychiatric or cognitive problems that would preclude them from program participation are excluded from the study. For assessment purposes, study participants need to have basic fluency in the Dutch language. Finally, patients participating in concurrent studies or rehabilitation programs containing elements of physical activity or exercise are also ineligible for the study.

Recruitment and randomization

In total 360 patients are being recruited from twelve community or university hospitals in the wider Amsterdam region of the Netherlands. All potentially eligible patients are identified by their medical oncologist or nurse practitioner, and receive written information about the trial. The patients are contacted by telephone to provide additional information about the trial and to confirm their eligibility. If the patient chooses to participate in the trial, (s)he is invited for an intake session where written informed consent is obtained and baseline assessments are made. Subsequently, patients are assigned to one of the three study groups by means of the minimization method [24], which is balanced on age, primary diagnosis, treating hospital and the use of trastuzumab.

Patients who decline to participate in the trial are asked to complete a one-time questionnaire assessing basic sociodemographic, attitudinal, and behavioral data, and to determine the reason(s) for non-participation.

Interventions

Patients are randomized to one of three study groups: Onco-Move, OnTrack, or usual care. The Onco-Move program aims at preserving cardiorespiratory fitness, as advocated by Mock [25]. The OnTrack program combines exercise for both cardiorespiratory fitness and muscle strength, as advocated by Courneya [15]. Both the Onco-Move and OnTrack program start in the week of the first cycle of chemotherapy and continue until three weeks after the last cycle of chemotherapy. At the end of chemotherapy all patients receive a leaflet providing encouragement and information on ways to be active.

Onco-Move

Onco-Move is a relatively low intensity, home-based, individualized, self-managed physical activity program developed and tested in a pilot study by the Comprehensive Cancer Centre Amsterdam (IKA). Based on the "Every Step Counts" program of Mock [25, 26], it uses self-management principles, aiming to maintain general physical fitness and preventing fatigue.

Trained nurses encourage patients to pursue an active lifestyle, 30 minutes per day, throughout the chemotherapy treatment, starting at the first chemotherapy session. Activities depend on patient preference, which may include walking, cycling, fitness training or swimming. Training with weights is not encouraged. At the first chemotherapy session, patients receive both verbal and written information about physical activity training, and specific advice about the desired intensity of activity based on the Borg Scale of perceived exertion (recommended level 12-14) [27]. The written information is based on the transtheoretical model of behavior [28, 29], called "active living" which identifies different stages of activity (pre-contemplation, contemplation, action, and maintenance).

The information patients receive about physical activity is tailored to their activity stage. For example, patients in the contemplation stage receive more information on why and how to become active, while patients in the maintenance stage receive information on how to stay active [28, 29]. Two weeks after the start of the program the nurse contacts the patient by telephone to inquire about how the program is going and if there is any additional information or advice needed. At each subsequent chemotherapy cycle, the nurse discusses program progress with the patient. Patients are asked to keep daily activity diaries, both to help them to monitor their own progress, and as an aid for the nurse to facilitate optimal use of the program.

OnTrack

The OnTrack is a relatively high intensity exercise program which is supervised by a physical therapist in an outpatient or general physical therapy practice setting. The pilot study showed that OnTrack was feasible in patients undergoing chemotherapy [30]. We are making use of the Onconet network of physical therapists in the region of North Holland who received special training in the OnTrack program. This facilitates patients to undergo the OnTrack program as close to home as possible.

In this program, patients are encouraged to be physically active for at least 30 minutes per day at Borg level 12-14 [27]. Like the Onco-Move program, patients are asked to keep a daily activity dairy. The physical therapists use the "active living" method to encourage daily physical activity. The physical therapist reviews the daily activity diary with the patient every three weeks.

Additionally, patients attend supervised exercise sessions two times per week. These sessions comprise exercises for warming up followed by exercises to maintain or increase muscle strength and exercises to maintain or increase aerobic capacity. Muscle strength exercises are performed for 20 minutes per session, starting with two series of 12 repetitions at 70% of the one repetition maximum (1RM) per exercise and increasing gradually to two series of eight repetitions at 80%1RM. Exercising in sets of two series is considered a sufficient, yet time efficient means of enhancing muscle strength, ensuring that all exercises can be performed during a session [31]. The resistance program consists of at least six exercises targeting the large muscle groups as follows: 1) vertical row (longissimus, biceps brachii, rhomboideus); 2) leg press (quadriceps, glutei, gastrocnemius); 3) bench press (pectoralis major, triceps); 4) pull over (pectoralis, triceps brachii, deltoideus, trapezius); 5) abdominal crunch (rectus abdominis); and 6) lunge (quadriceps, glutei, hamstrings). Additional exercises can be added according to patients' preferences.

For patients with breast cancer who have had axillary lymph node dissection, a modified strength training program is used for the upper extremities, consisting of two series of 15 repetitions for each exercise with the lightest possible weight, which is increased with the smallest possible step when the two series can be completed without symptoms of lymph edema [32].

Aerobic exercises are performed for 30 minutes per session (with a minimal duration of ten minutes per exercise), with an intensity of 50% to 80% of the maximal workload (Wmax) as estimated by the Steep Ramp Test [33]. The intensity of the aerobic exercises are increased if a patient scores a 12 or lower on the Borg scale of perceived exertion, while the intensity is decreased at a score of 16 or higher [27]. The heart rate should be within a heart rate zone of 60% to 90% of the maximal heart rate, which is conventionally estimated as 220 minus age.

Usual care

Usual care will vary according to hospital guidelines and doctors' and patients' preferences. Although usual care can not be standardized, it will not involve routine, systematic exercises.

Study outcomes

All study outcomes, with the exception of return to work, compliance and satisfaction with the interventions, are assessed prior to randomization (T0), at the completion of chemotherapy (T1), and at 6 month follow-up (T2). Return to work is assessed at T1 and T2, while compliance and satisfaction are assessed at T1 only, and only in the two intervention groups.

To facilitate comparison of results across the A-CaRe studies, the outcome measures used in these four clinical trials have been harmonized to as great an extent as possible.

Primary outcome measures

Cardiorespiratory fitness

Cardiorespiratory fitness is being assessed with the steep ramp test (an incremental bicycle ergometer test) and a cycle endurance test. Both tests are completed on a calibrated, electronically-braked cycle ergometer (Corival, Lode, Groningen, The Netherlands). For the steep ramp test, the patient is instructed to cycle at a speed between 70 and 80 revolutions per minute (RPM), starting with a 3 minutes warming-up at 10 Watts. The test starts at 25 Watts, after which the load is increased by 25 Watts every 10 seconds. The test ends if cycling speed falls below 60 RPM. Maximal workload (Wmax), time cycled at that load, and heart rate at the end of the test are recorded. The steep ramp test has been shown to be a reliable (ICC = 0.996) and valid (correlation with peak oxygen uptake (peakVO2) of 0.85) means of estimating maximal workload in patients with cancer. PeakVO2 can be estimated from the steep ramp test using a linear regression equation [33].

Exercise endurance is measured after a period of rest following the steep ramp test. The cycle endurance test is done at a workload based on 70% of the Wmax reached during the steep ramp test. After a one-minute warming-up on the same ergometer that was used for the steep ramp test, the load is increased to the predetermined workload. The patient continues cycling at this constant submaximal workload until the cycling speed falls below 60 RPM, with a maximum time of 30 minutes. The endurance time and heart rate at the end of the test are recorded. The workload of the endurance test used at follow up measurements is the same as that of the baseline endurance test.

Muscle strength

Upper extremity muscle strength is measured with the JAMAR® grip strength dynamometer [34] and the microFET® hand held dynamometer (HHD) for the elbow flexion, using a standardized measurement protocol [35]. Lower extremity muscle strength is tested with the microFET® HHD for the extension of the knee, again using a standardized measurement protocol [36], and with the 30 s chair stands test. During the 30 s chair stands test patients are asked to stand up from a chair with their arms folded across the chest, then to sit down again. The action is repeated at their fastest pace over a 30 second period. The final test score is the number of times that the patient rises to a full stand from the seated position with arms folded within 30 s. The 30 s chair stands test has been shown to be a valid and reliable measure of proximal lower limb strength in older adults [37].

Fatigue

Fatigue symptoms are assessed with the Multidimensional Fatigue Inventory (MFI) [38]. The MFI is composed of 20 items, organized into five scales: general fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue. Questions are posed about the past few days, and responses are recorded on a five-point scale.

In addition to the MFI patients are asked to complete the Fatigue Quality List (FQL) [39], assessing patients' perception and appraisal of experienced fatigue. The FQL consists of 25 adjectives describing the fatigue experience, organized into 4 subscales: frustrating, exhausting, pleasant, and frightening.

Secondary study outcomes

Secondary outcomes are mood disturbance, quality of sleep, health-related quality of life, functioning in daily life, measured physical activity level, self-reported physical activity level, anthropometric measures, return to work, chemotherapy completion rates, compliance, satisfaction with the intervention, adverse effects and costs from a societal perspective. A complete overview of assessments and instruments are presented in Table 1. A small selection of these measures is described in detail.

Table 1 Outcome measures
Full size table

Measured physical activity level

The level of physical activity will be objectively measured with the Actigraph (Actigraph, Fort Walton Beach Florida, USA), a small accelerometer which can measure accelerations from 0.05 to 2.00 G [40]. These accelerations are scored in counts per minute that provide information about how long and how intensive a patient has been physically active. The epoch will be set at 5 seconds. Patients wear the accelerometer on the right hip for 5 days including at least one weekend day. The Actigraph will not give any form of feedback to the participant.

Chemotherapy completion rates

Chemotherapy completion rate will be assessed as the average relative dose-intensity for the originally planned regimen based on standard formulas [41]. The data will be obtained via medical records.

Costs from a societal perspective

For cost-utility purposes, the EQ-5D, a brief HRQoL measurement, is included in the questionnaire package [42]. Health care costs, patient and family costs, and production losses will be assessed, and relevant data will be collected thought retrospective cost diaries measured on a monthly basis during the entire study period.

Sociodemographic and clinical data

At baseline, sociodemographic data (e.g., age, gender, education, marital status, living and work situation), and lifestyle variables (e.g., smoking history), are being obtained via questionnaire.

Clinical information, including (date of) diagnosis, tumor characteristics, treatment (e.g., type of surgery, chemotherapy regimen), hemoglobin levels and medication use will be abstracted from the medical records. During the follow-up period, data on disease status (progression/recurrence) and any additional treatment (e.g., endocrine therapy, trastuzumab) is obtained via medical records and self-report.

Moderating variables

A series of questions is posed to assess potential moderating variables, and variables that may be predictive of compliance with the physical exercise and activity programs. These include items assessing attitudes towards and beliefs about physical activity, social influence from peers, barriers to and perceived benefits of physical activity, self-efficay towards physical activity and stage of change [43–46]. Patients' preferences for type of exercise intervention is also being assessed [21].

Non-participant analysis

In previous studies of exercise programs among patients with cancer, the generalizability of the results was limited due to a relatively low participation or uptake rate [13, 14]. We expect that, in the current trial, a substantial percentage of eligible patients will decline the invitation to participate in the trial. We hypothesize that patients who choose not to participate have been less physical active and have led a more sedentary lifestyle prior to becoming ill than those who participate. We also expect that they have less favorable attitudes towards physical exercise, in general, and during chemotherapy treatment, in particular. Sociodemographic characteristics, fatigue and attitudes and behaviors with regard to physical exercise of the non-participants will be compared with those of the trial participants, using appropriate statistics (e.g. students t-test, chi square, etc.).

Power calculation

The primary study outcomes include two performance measures (cardiorespiratory fitness and muscle strength) and self-reported fatigue. It is expected that patients in the usual care condition will experience a 5%-10% decline in physical fitness during their chemotherapy treatment, that this will improve gradually during the post-treatment period, but will not necessarily return to pretreatment levels. It is hypothesized that the OnTrack program will yield at least a 20% improvement in general physical fitness. Based on the results of Courneya et al., a pretreatment mean for the 1-repetition maximum for leg extension is estimated to be 25 kg, with a standard deviation of 12 kg [15]. We expect that the Onco-Move program will help patients to maintain their pretreatment levels of cardiorespiratory fitness, but not necessarily improve, and that it will have little or no effect on muscle strength.

Based on the above figures, 100 patients per group are needed to detect a 0.40 standard deviation difference (Cohen's effect size [47]) in performance-based outcomes between the OnTrack group and the usual care group at the post-chemotherapy assessment, with power set at 0.80 and alpha at 0.05 (two-sided test).

We will recruit 360 patients into the trial to allow for an attrition of approximately 20% (i.e., patients who discontinue participation in the trial entirely, including failure to complete follow-up assessments). These numbers will be sufficient to detect a one-half standard deviation unit difference in self-reported fatigue. This magnitude of difference is generally considered to be indicative of clinically meaningful differences in patients' self-reported symptom experience [47, 48].

Statistical analyses

All primary statistical analyses will be conducted on an intention-to-treat basis. Between group differences over time in performance indicators of general physical condition and muscle strength will be evaluated using multilevel regression analysis for % change from baseline, and two factor (group × time) multivariate analysis of variance with repeated measures on the time factor for comparison of mean scores. Scores on the self-report measures of fatigue, mood state and HRQoL will be calculated according to published scoring algorithms. Between-group differences over time in mean scores will be tested using a two factor (group × time) multivariate analysis of variance with repeated measures on the time factor. Effect sizes will be calculated using standard statistical procedures.

Supplementary analyses will be carried out in which data relating to compliance with the program elements are taken into account. Specifically, we will determine whether the level of compliance (based on attendance records and self-report data) is associated significantly with the changes over time in physical condition, muscle strength, fatigue, mood, and HRQoL. Similarly, we will investigate whether program effectiveness varies significantly as a function of patients' background characteristics, and particularly those variables assessing life style, health behavior and health attitudes.

Cost-effectiveness analysis

This study also includes both incremental cost-effectiveness and cost-utility analyses. The cost-effectiveness ratio is calculated by dividing the difference between the mean total costs of the exercise and control groups by the difference in mean primary clinical effects of the groups [49]. In this analysis both direct and indirect costs will be taken into account. The incremental cost-utility ratio expresses the additional costs of the intervention per quality-adjusted life year (QALY) gained, compared to the usual care control group.

Discussion

Compromised physical fitness and increasing fatigue are common side effects of cancer chemotherapy. Exercise during chemotherapy is a promising strategy for intervening at any earlier stage, to minimize or even prevent side effects both in the short- and long-term. Previous studies investigating the value of physical exercise during treatment have yielded inconsistent results, and many studies exhibited a range of methodological limitations.

In the current trial, we are evaluating the effectiveness and cost-effectiveness of a low intensity, home-based physical activity program, and a structured, supervised, moderate intensity exercise program in maintaining or enhancing physical fitness (cardiorespiratory fitness and muscle strength), in minimizing fatigue, and in enhancing HRQoL of patients undergoing adjuvant chemotherapy for breast cancer or colon cancer.

Our trial has several strengths, including: (1) the randomized trial design; (2) the multicenter nature of the trial; (3) the large sample size; (4) the relatively long-term follow-up; (5) the head-to-head comparison of two interventions varying in nature and intensity; (6) inclusion of both performance based and self-reported outcomes; (7) the use of intention-to-treat analysis; (8) the inclusion of a cost-effectiveness and cost-utility evaluation; and (9) the detailed evaluation of the background, attitudes and behavior of patients who decline to participate in the trial.

Several limitations of the trial should also be noted. First, although direct peakVO2 measurements are considered the gold standard for assessing cardiorespiratory fitness, these are not feasible in our trial because of the number and geographical spread of the training locations, and the (travel) time and costs involved with centralized measurements. However, it can be argued that an improvement in cycle endurance time may be more clinically relevant than an improvement in peakVO2 [50, 51]. Second, although the usual care control group will not be provided with any materials or programs elements relating to physical exercise, clinicians and ancillary health care providers are increasingly recognizing the potential value of physical activity both during and following cancer treatment. Thus we cannot rule out the possibility that some patients in the control group will be encouraged to increase their level of physical activity, either by their caregivers or via the media. Nevertheless, we do not anticipate that this will take place in a structured or systematic way, and thus the planned comparisons (between the two intervention groups and the control group) will still be valid.

In summary, given the increasing number of patients with cancer, and improving survival rates, it is important to ensure that patients' physical and psychosocial health is maintained or even enhanced to as great an extent as possible both during active treatment and once treatment has been completed. Encouraging and facilitating physical activity during treatment may enhance health outcomes in both the short- and long-term.

Abbreviations

PACES:

Physical exercise during Adjuvant Chemotherapy Effectiveness Study

A-CaRe:

Alpe d'HuZes Cancer Rehabilitation

HRQoL:

Health-related quality of life

RPM:

revolutions per minute

Wmax:

Maximal workload

peakVO2 :

peak oxygen uptake

HHD:

hand held dynamometer

QALY:

quality-adjusted life year

References

  1. Courneya KS: Exercise in cancer survivors: an overview of research. Med Sci Sports Exerc. 2003, 35: 1846-1852. 10.1249/01.MSS.0000093622.41587.B6.

    Article  PubMed  Google Scholar 

  2. Courneya KS, Friedenreich CM: Physical exercise and quality of life following cancer diagnosis: a literature review. Ann Behav Med. 1999, 21: 171-179. 10.1007/BF02908298.

    Article  CAS  PubMed  Google Scholar 

  3. Hartvig P, Aulin J, Hugerth M, Wallenberg S, Wagenius G: Fatigue in cancer patients treated with cytotoxic drugs. J Oncol Pharm Pract. 2006, 12: 155-164. 10.1177/1078155206070774.

    Article  CAS  PubMed  Google Scholar 

  4. Sitzia J, Dikken C: Survey of the incidence and severity of side effects reported by patients receiving six cycles of FEC chemotherapy. J Cancer Nurs. 1997, 1: 61-73. 10.1016/S1364-9825(97)80184-8.

    Article  Google Scholar 

  5. Stone P, Richardson A, Ream E, Smith AG, Kerr DJ, Kearney N: Cancer-related fatigue: inevitable, unimportant and untreatable? Results of a multi-centre patient survey. Cancer Fatigue Forum. Ann Oncol. 2000, 11: 971-975. 10.1023/A:1008318932641.

    Article  CAS  PubMed  Google Scholar 

  6. Lucia A, Earnest C, Perez M: Cancer-related fatigue: can exercise physiology assist oncologists?. Lancet Oncol. 2003, 4: 616-625. 10.1016/S1470-2045(03)01221-X.

    Article  PubMed  Google Scholar 

  7. Mock V, Pickett M, Ropka ME, Muscari Lin E, Stewart KJ, Rhodes VA, McDaniel R, Grimm PM, Krumm S, McCorkle R: Fatigue and quality of life outcomes of exercise during cancer treatment. Cancer Pract. 2001, 9: 119-127. 10.1046/j.1523-5394.2001.009003119.x.

    Article  CAS  PubMed  Google Scholar 

  8. Mock V, Burke MB, Sheehan P, Creaton EM, Winningham ML, McKenney-Tedder S, Schwager LP, Liebman M: A nursing rehabilitation program for women with breast cancer receiving adjuvant chemotherapy. Oncol Nurs Forum. 1994, 21: 899-907.

    CAS  PubMed  Google Scholar 

  9. Schwartz AL: Fatigue mediates the effects of exercise on quality of life. Qual Life Res. 1999, 8: 529-538. 10.1023/A:1008978611274.

    Article  CAS  PubMed  Google Scholar 

  10. Adamsen L, Midtgaard J, Rorth M, Borregaard N, Andersen C, Quist M, Moller T, Zacho M, Madsen JK, Knutsen L: Feasibility, physical capacity, and health benefits of a multidimensional exercise program for cancer patients undergoing chemotherapy. Support Care Cancer. 2003, 11: 707-716. 10.1007/s00520-003-0504-2.

    Article  PubMed  Google Scholar 

  11. Campbell A, Mutrie N, White F, McGuire F, Kearney N: A pilot study of a supervised group exercise programme as a rehabilitation treatment for women with breast cancer receiving adjuvant treatment. Eur J Oncol Nurs. 2005, 9: 56-63. 10.1016/j.ejon.2004.03.007.

    Article  PubMed  Google Scholar 

  12. Segal R, Evans W, Johnson D, Smith J, Colletta S, Gayton J, Woodard S, Wells G, Reid R: Structured exercise improves physical functioning in women with stages I and II breast cancer: results of a randomized controlled trial. J Clin Oncol. 2001, 19: 657-665.

    CAS  PubMed  Google Scholar 

  13. Courneya KS, Sellar CM, Stevinson C, McNeely ML, Peddle CJ, Friedenreich CM, Tankel K, Basi S, Chua N, Mazurek A, et al: Randomized Controlled Trial of the Effects of Aerobic Exercise on Physical Functioning and Quality of Life in Lymphoma Patients. J Clin Oncol. 2009

    Google Scholar 

  14. Mutrie N, Campbell AM, Whyte F, McConnachie A, Emslie C, Lee L, Kearney N, Walker A, Ritchie D: Benefits of supervised group exercise programme for women being treated for early stage breast cancer: pragmatic randomised controlled trial. BMJ. 2007, 334: 517-10.1136/bmj.39094.648553.AE.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Courneya KS, Segal RJ, Mackey JR, Gelmon K, Reid RD, Friedenreich CM, Ladha AB, Proulx C, Vallance JK, Lane K, et al: Effects of aerobic and resistance exercise in breast cancer patients receiving adjuvant chemotherapy: a multicenter randomized controlled trial. J Clin Oncol. 2007, 25: 4396-4404. 10.1200/JCO.2006.08.2024.

    Article  PubMed  Google Scholar 

  16. Cheema B, Gaul CA, Lane K, Fiatarone Singh MA: Progressive resistance training in breast cancer: a systematic review of clinical trials. Breast Cancer Res Treat. 2008, 109: 9-26. 10.1007/s10549-007-9638-0.

    Article  PubMed  Google Scholar 

  17. Galvao DA, Newton RU: Review of exercise intervention studies in cancer patients. J Clin Oncol. 2005, 23: 899-909. 10.1200/JCO.2005.06.085.

    Article  PubMed  Google Scholar 

  18. Knols R, Aaronson NK, Uebelhart D, Fransen J, Aufdemkampe G: Physical exercise in cancer patients during and after medical treatment: a systematic review of randomized and controlled clinical trials. J Clin Oncol. 2005, 23: 3830-3842. 10.1200/JCO.2005.02.148.

    Article  PubMed  Google Scholar 

  19. Kuchinski AM, Reading M, Lash AA: Treatment-related fatigue and exercise in patients with cancer: a systematic review. Medsurg Nurs. 2009, 18: 174-180.

    PubMed  Google Scholar 

  20. Markes M, Brockow T, Resch KL: Exercise for women receiving adjuvant therapy for breast cancer. Cochrane Database Syst Rev. 2006, CD005001-

    Google Scholar 

  21. Courneya KS, McKenzie DC, Mackey JR, Gelmon K, Reid RD, Friedenreich CM, Ladha AB, Proulx C, Vallance JK, Lane K, et al: Moderators of the effects of exercise training in breast cancer patients receiving chemotherapy: a randomized controlled trial. Cancer. 2008, 112: 1845-1853. 10.1002/cncr.23379.

    Article  PubMed  Google Scholar 

  22. Courneya KS, Friedenreich CM, Reid RD, Gelmon K, Mackey JR, Ladha AB, Proulx C, Vallance JK, Segal RJ: Predictors of follow-up exercise behavior 6 months after a randomized trial of exercise training during breast cancer chemotherapy. Breast Cancer Res Treat. 2009, 114: 179-187. 10.1007/s10549-008-9987-3.

    Article  PubMed  Google Scholar 

  23. Moher D, Schulz KF, Altman DM: The CONSORT statement: revised recommendations for improving the quality of reports of parallel group randomized trails. BMC Med Res Methodol. 2001, 1: 2-10.1186/1471-2288-1-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Scott NW, McPherson GC, Ramsay CR, Campbell MK: The method of minimization for allocation to clinical trials. a review. Control Clin Trials. 2002, 23: 662-674. 10.1016/S0197-2456(02)00242-8.

    Article  PubMed  Google Scholar 

  25. Mock V, Cameron L, Tompkins C, Lin E, Stewart K: Every Step Counts; A walking Exercise Program for Persons With Cancer. 2008, Baltimore: The John Hopkins University

    Google Scholar 

  26. Watson T, Mock V: Exercise as an intervention for cancer-related fatigue. Phys Ther. 2004, 84: 736-743.

    PubMed  Google Scholar 

  27. Borg G: Borg's Perceived Exertion and Pain Scales. 2010, Champaign, IL: Human Kinetic

    Google Scholar 

  28. van der Ploeg HP, Streppel KR, van der Beek AJ, van der Woude LH, Vollenbroek-Hutten MM, van Harten WH, van Mechelen W: Counselling increases physical activity behaviour nine weeks after rehabilitation. Br J Sports Med. 2006, 40: 223-229. 10.1136/bjsm.2005.021139.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. van der Ploeg HP, Streppel KR, van der Beek AJ, van der Woude LH, Vollenbroek-Hutten MM, van Harten WH, van Mechelen W: Successfully improving physical activity behavior after rehabilitation. Am J Health Promot. 2007, 21: 153-159.

    Article  PubMed  Google Scholar 

  30. Geleijn E, Smeets C, Vrijman M, Kroon D, Boven E, Stuiver M: Cytofys, behoud van kracht en conditie tijden de chemotherapie. Nederlands Tijdschrift voor Oncologie.

  31. Galvao DA, Taaffe DR: Single- vs. multiple-set resistance training: recent developments in the controversy. J Strength Cond Res. 2004, 18: 660-667.

    PubMed  Google Scholar 

  32. Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, Flechtner H, Fleishman SB, De Haes JC, et al: The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993, 85: 365-376. 10.1093/jnci/85.5.365.

    Article  CAS  PubMed  Google Scholar 

  33. De Backer IC, Schep G, Hoogeveen A, Vreugdenhil G, Kester AD, van Breda E: Exercise testing and training in a cancer rehabilitation program: the advantage of the steep ramp test. Arch Phys Med Rehabil. 2007, 88: 610-616. 10.1016/j.apmr.2007.02.013.

    Article  PubMed  Google Scholar 

  34. Trutschnigg B, Kilgour RD, Reinglas J, Rosenthall L, Hornby L, Morais JA, Vigano A: Precision and reliability of strength (Jamar vs. Biodex handgrip) and body composition (dual-energy X-ray absorptiometry vs. bioimpedance analysis) measurements in advanced cancer patients. Appl Physiol Nutr Metab. 2008, 33: 1232-1239. 10.1139/H08-122.

    Article  PubMed  Google Scholar 

  35. van der Ploeg RJ, Fidler V, Oosterhuis HJ: Hand-held myometry: reference values. J Neurol Neurosurg Psychiatry. 1991, 54: 244-247. 10.1136/jnnp.54.3.244.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Knols RH, Aufdemkampe G, de Bruin ED, Uebelhart D, Aaronson NK: Hand-held dynamometry in patients with haematological malignancies: measurement error in the clinical assessment of knee extension strength. BMC Musculoskelet Disord. 2009, 10: 31-10.1186/1471-2474-10-31.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Jones CJ, Rikli RE, Beam WC: A 30-s chair-stand test as a measure of lower body strength in community-residing older adults. Res Q Exerc Sport. 1999, 70: 113-119.

    Article  CAS  PubMed  Google Scholar 

  38. Smets EM, Garssen B, Bonke B, De Haes JC: The Multidimensional Fatigue Inventory (MFI) psychometric qualities of an instrument to assess fatigue. J Psychosom Res. 1995, 39: 315-325. 10.1016/0022-3999(94)00125-O.

    Article  CAS  PubMed  Google Scholar 

  39. Gielissen MF, Knoop H, Servaes P, Kalkman JS, Huibers MJ, Verhagen S, Bleijenberg G: Differences in the experience of fatigue in patients and healthy controls: patients' descriptions. Health Qual Life Outcomes. 2007, 5: 36-10.1186/1477-7525-5-36.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Bassett DR, Ainsworth BE, Swartz AM, Strath SJ, O'Brien WL, King GA: Validity of four motion sensors in measuring moderate intensity physical activity. Med Sci Sports Exerc. 2000, 32: S471-S480. 10.1097/00005768-200009001-00006.

    Article  PubMed  Google Scholar 

  41. Longo DL, Duffey PL, DeVita VT, Wesley MN, Hubbard SM, Young RC: The calculation of actual or received dose intensity: a comparison of published methods. J Clin Oncol. 1991, 9: 2042-2051.

    CAS  PubMed  Google Scholar 

  42. Uyl-de Groot CA, Rutten FF, Bonsel GJ: Measurement and valuation of quality of life in economic appraisal of cancer treatment. Eur J Cancer. 1994, 30A: 111-117. 10.1016/S0959-8049(05)80030-9.

    Article  CAS  PubMed  Google Scholar 

  43. Marcus BH, Selby VC, Niaura RS, Rossi JS: Self-efficacy and the stages of exercise behavior change. Res Q Exerc Sport. 1992, 63: 60-66.

    Article  CAS  PubMed  Google Scholar 

  44. Sallis JF, Calfas KJ, Alcaraz JE, Gehrman C, Johnson MF: Potential mediators of change in a physical activity promotion course for university students: Project GRAD. Ann Behav Med. 1999, 21: 149-158. 10.1007/BF02908296.

    Article  CAS  PubMed  Google Scholar 

  45. Biddle S, Goudas M, Page A: Social-psychological predictors of self-reported actual and intended physical activity in a university workforce sample. Br J Sports Med. 1994, 28: 160-163. 10.1136/bjsm.28.3.160.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Aizen I, Madden TJ: Prediction of goal-directed behavior: Attitudes and perceived behavioral control. J Exp Soc Psychol. 1986, 22: 453-474. 10.1016/0022-1031(86)90045-4.

    Article  Google Scholar 

  47. Cohen J: Statistical power analysis for the behavioral sciences. 1988, Hillsdale, NJ: Lawrence Erlbaum

    Google Scholar 

  48. Norman GR, Wyrwich KW, Patrick DL: The mathematical relationship among different forms of responsiveness coefficients. Qual Life Res. 2007, 16: 815-822. 10.1007/s11136-007-9180-x.

    Article  CAS  PubMed  Google Scholar 

  49. Drummond MF, Sculpher MJ, Torrance GW, O'Brien BJ, Stoddart GL: Methods for the economic evaluation of health care programmes. 2005, New York: Oxford University Press

    Google Scholar 

  50. Laviolette L, Bourbeau J, Bernard S, Lacasse Y, Pepin V, Breton MJ, Baltzan M, Rouleau M, Maltais F: Assessing the impact of pulmonary rehabilitation on functional status in COPD. Thorax. 2008, 63: 115-121. 10.1136/thx.2006.076844.

    Article  CAS  PubMed  Google Scholar 

  51. Ong KC, Chong WF, Soh C, Earnest A: Comparison of different exercise tests in assessing outcomes of pulmonary rehabilitation. Respir Care. 2004, 49: 1498-1503.

    PubMed  Google Scholar 

  52. Zigmond AS, Snaith RP: The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983, 67: 361-370. 10.1111/j.1600-0447.1983.tb09716.x.

    Article  CAS  PubMed  Google Scholar 

  53. Buysse DJ, Reynolds CF, Monk TH, Berman SR, Kupfer DJ: The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989, 28: 193-213. 10.1016/0165-1781(89)90047-4.

    Article  CAS  PubMed  Google Scholar 

  54. Cardol M, Beelen A, van den Bos GA, de Jong BA, de Groot IJ, de Haan RJ: Responsiveness of the Impact on Participation and Autonomy questionnaire. Arch Phys Med Rehabil. 2002, 83: 1524-1529. 10.1053/apmr.2002.35099.

    Article  PubMed  Google Scholar 

  55. Washburn RA, McAuley E, Katula J, Mihalko SL, Boileau RA: The physical activity scale for the elderly (PASE): evidence for validity. J Clin Epidemiol. 1999, 52: 643-651. 10.1016/S0895-4356(99)00049-9.

    Article  CAS  PubMed  Google Scholar 

  56. Ketel IJ, Volman MN, Seidell JC, Stehouwer CD, Twisk JW, Lambalk CB: Superiority of skinfold measurements and waist over waist-to-hip ratio for determination of body fat distribution in a population-based cohort of Caucasian Dutch adults. Eur J Endocrinol. 2007, 156: 655-661. 10.1530/EJE-06-0730.

    Article  CAS  PubMed  Google Scholar 

Pre-publication history

Download references

Acknowledgements

The PACES study is supported by the Alpe d'HuZes/KWF Fund. The research grant is provided by the Dutch Cancer Society (grant number ALPE 2009-4299). This trial is part of the A-Care Program, http://www.a-care.org. The authors acknowledge the A-CaRe Clinical Research group.

A.J.H. Hellendoorn - van Vreeswijk, V.A. Bouwman and colleagues of the Comprehensive Cancer Centre Amsterdam developed Onco-Move. The Department of Physical Therapy of the VU Medical Center, Motion Physical Therapy, and the Department of Physical Therapy of the Antoni van Leeuwenhoek Hospital developed OnTrack. E. Geleijn and R.J. Huijsmans of the VU Medical Centre are responsible for the coordination of Onconet http://www.onconet.nu.

Participating hospitals: Amstelland Hospital, Antoni van Leeuwenhoek Hospital, BovenIJ Hospital, Flevohospital, Medical Center Alkmaar, Onze Lieve Vrouwe Gasthuis, Rode Kruis Hospital, Sint Lucas Andreas Hospital, Spaarne Hospital Hoofddorp, VU Medical Center Amsterdam, Waterland Hospital, Zaans Medical Center.

Participating physical therapist: Algera Physical Therapy, Donkers & Hilbers Physical Therapy, MOVE Akersloot, Motion Physical Therapy, Paramedisch Adviescentrum Aalsmeer, Physical Therapy Amstelland Hospital, Physical Therapy Antoni van Leeuwenhoek Hospital, Physical Therapy BovenIJ Hospital, Physical Therapy Elsbroek, Physical Therapy Flevohospital, Physical Therapy Medical Centre Alkmaar, Physical Therapy Medi-mere, Physical Therapy Muiderslotweg, Physical Therapy Onze Lieve Vrouwe Gasthuis, Physical Therapy Rode Kruis Hospital, Physical Therapy Sint Lucas Andreas Hospital, Physical Therapy Spaarne Hospital, Physical Therapy VU Medical Centre, Physical Therapy Waterland Hospital, Physical Therapy Zaans Medical Center, Practice Deen, Practice Nijdam, Refysio.

Author information

Authors and Affiliations

  1. The Netherlands Cancer Institute, Division of Psychosocial Research and Epidemiology, Amsterdam, The Netherlands

    Hanna van Waart, Wim H van Harten & Neil K Aaronson

  2. The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Physical therapy, Amsterdam, The Netherlands

    Martijn M Stuiver

  3. The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Medical Oncology, Amsterdam, The Netherlands

    Gabe S Sonke

Authors
  1. Hanna van Waart
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Martijn M Stuiver
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wim H van Harten
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gabe S Sonke
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Neil K Aaronson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Neil K Aaronson.

Additional information

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

NA, WvH, MS and GS are the principal investigators of this trial. HvW is the PhD student of this trial, and generated the first draft of this manuscript based on the original study protocol. All authors approved the final version of the manuscript.

Authors’ original submitted files for images

Below are the links to the authors’ original submitted files for images.

Authors’ original file for figure 1

Rights and permissions

Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reprints and permissions

About this article

Cite this article

van Waart, H., Stuiver, M.M., van Harten, W.H. et al. Design of the Physical exercise during Adjuvant Chemotherapy Effectiveness Study (PACES):A randomized controlled trial to evaluate effectiveness and cost-effectiveness of physical exercise in improving physical fitness and reducing fatigue. BMC Cancer 10, 673 (2010). https://doi.org/10.1186/1471-2407-10-673

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/1471-2407-10-673

Keywords

BMC Cancer

ISSN: 1471-2407

Contact us