Effects of aerobic exercise training on physical performance during myeloablative therapy

Reviewer: Arpi Thukral, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: June 2, 2008

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Presenter: Maike de Wit
Presenter's Affiliation: University Clinicof Hamburg, Hamburg, Germany
Type of Session: Scientific

Background

  • The effects of cancer treatment during long or recurrent hospitalizations can induce loss of physical performance of patients.
    • Prolonged physical inactivity can cause deconditioning and cause patients to lose their functional reserve.
    • Reductions in activity can cause muscle atrophy and reductions in bone density, which may lead to diminished musculoskeletal strength and performance.
    • This loss of physical performance can be very debilitating to patients, not only during their treatment, but in later years as well
  • Myeloablative therapy refers to cancer treatment that kills (ablates) the myeloid stem cells in the bone marrow (the cells that produce new blood cells).
    • Patients treated with this therapy have a propensity to become severely ill since they are immunocompromised, and thus they are often hospitalized for long periods of time. This makes them an ideal population in which to study effects of exercise training on physical performance.
  • Previous studies have suggested that exercise has benefits for people with cancer, and these include increases in cardiovascular and pulmonary functioning, increase in muscle function, improved oxygen consumption, and increased strength.
    • Cancer treatment can have lasting effects on various organ systems, and it is proposed that the benefits of exercise may help to alleviate some of these harmful long-term effects.
  • The purpose of this study was to evaluate effects of anaerobic exercise training on physical performance of patients with hematologic malignancies or solid tumors during myeloablative therapy or high-dose chemotherapy followed by autologous peripheral blood stem cell transplant.
    • The questions to be answered by the authors were
      • 1) Is exercise feasible in this group of patients?
      • 2) What happens to physical performance in these patients if they do exercise?

Materials and Methods

  • This study is a prospective, randomized controlled study where 85 patients were randomly assigned to a training group or control group. 
  • The training group followed an exercise regimen which consisted of an individually supervised exercise program with an ergometer  (an exercise machine that can measure work performed) training for 10 min, and 3 exercises using the main muscle groups for 20 minutes, all for 5 times per week during hospitalization.
  • The control arm did not exercise, but met with a physiotherapist daily as indicated throughout the hospitalization. All patients in both groups completed a daily questionnaire to assess treatment- related side effects and quality of life (QOL). All patients were undergoing myeloablative therapy. Assessment of physical performance was done by using spirogometry (including lactate controls), immune system function with flow cytometry, and blood samples. Interruptions in exercise were allowed for infections, fevers, platelets<10, Hbg<8, and ICU stays.
  • Exclusion criteria:
    • Patients with cardiovascular disease or ventricular rhythm disorders.
    • Patient with BMI<18 or BMI>30.
    • Patients with untreated hypertension. 
    • Patients with other chronic diseases. 
  • The primary endpoint was change in physical performance between the beginning and end of treatment, measured in Watts (W). 
    • The study was powered to require 25 patients in each group in order to note a difference between the two. 
  • Secondary endpoints included lung function, side effects, days of hospital stay, QOL, and immunologic parameters.  QOL assessment was performed with the EORTC assessment measure and the MFIS scale. 

Results

  • Between 2006 and 2007 (over a 1 year period), 58 patients were randomly assigned to a training group (TG, n=29) or a control group (CG, n=29) group. 
  • In terms of the primary endpoint (change in physical performance), there was a significant increase in physical performance in the TG (8.96 +/-24 W) and a decrease in the CG (-7.24 +/- 20 W), p=0.021.
  • At a 2 mmol/ml blood lactate concentration, the TG had significantly higher oxygen consumption (V02, p=0.03) and minute ventilation (VE, p=0.04) compared to the CG.
  • There were no significant differences seen between the 2 groups for the following side effects: infection, diarrhea, vomiting, fevers, muscle pain, and antiemetic use. 
    • However, on a subjective scale, the TG did have significantly less fatigue compared to the CG (p=0.03). 
  • The days of hospital stay between the TG and CG also did not differ significantly, and were 28.5 days and 31.1 days, respectively. 
  • The TG did have an increase in physical functioning score (p=0.04). 
  • 8 patients died in the TG and 12 died in the CG. 

Author's Conclusions

  • This study demonstrated that there are positive effects of aerobic exercise on the physical performance and treatment-related symptoms during myeloablative chemotherapy. 
    • Patients tend to be fitter and feel better at discharge if they undergo regular aerobic exercise. 
  • An improvement in lung function can also be seen in patients treated with exercise. 
  • Cancer patients should have enhanced physical activity intervention during their hospitalizations.

Clinical/Scientific Implications

  • Even before treatment begins, it has been shown that cancer cells circulating in the body can decrease a patient’s physical reserve. With cancer treatment and recurrent and prolonged hospitalizations, this reserve likely declines even further due to physical inactivity. 
  • The authors make a valiant attempt to study exercise in a cancer patient population in which it may be most beneficial. There is a currently a paucity of randomized trials studying this topic. 
  • Strengths of the study:
    • It is a randomized trial, with long-term (1 year) follow up.
    • The exercise program administered appears safe, well tolerated, and well designed with an achievable "dose" of about 30-40 minutes/day. 
    • The change in physical performance was measured quantitatively as the amount of work a person can do with aerobic activity.
    • QOL of life measures were assessed with proper tools.
  • Limitations of the study:
    • There was no information presented to help quantify the functional reserve of a patient at 1 year.
    • They had a very small sample size, and this was done as a pilot or feasibility study, and therefore generalizable conclusions are difficult to draw from this data.
    • There was no information on body weight or composition changes (especially % of muscle mass relative fat). 
    • There was no information on follow-up data for functional status.
    • One question that was also not answered is why the mortality rate was 30% lower in the TG.
  • Although this study had some limitations and had a small patient population, it was ultimately a well conceived and well conducted randomized trial. 
  • The exercise regimen during myeloablative therapy appears to be achievable, effective, and safe, and may help to preserve physical function in these patients. Ultimately, this can reduce the risk for limitations and disabilities in patients later in life. 
  • This data adds to the current literature on exercise in cancer patients, but future studies would need to be done in larger cohorts in order to answer the questions outlined above. Analyses on feasibility of implementation of such exercise programs in hospitals may also be beneficial. 

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