Elsevier

The Lancet Oncology

Volume 10, Issue 6, June 2009, Pages 598-605
The Lancet Oncology

Review
Exercise intolerance in cancer and the role of exercise therapy to reverse dysfunction

https://doi.org/10.1016/S1470-2045(09)70031-2Get rights and content

Summary

Exercise tolerance reflects the integrative capacity of components in the oxygen cascade to supply adequate oxygen for ATP resynthesis. Conventional cancer therapies can simultaneously affect one or more components of this cascade and reduce the body's ability to deliver or utilise oxygen and substrate, leading to exercise intolerance. We propose that molecularly-targeted therapy is associated with a further, more subtle, negative effect on the components that regulate exercise limitation. We outline possible causes of exercise intolerance in patients with cancer and the role of exercise therapy to mitigate or prevent dysfunction. We also discuss possible implications for exercise-regulated gene expression for cancer biology and treatment efficacy. A better understanding of these issues might lead to more effective integration of exercise therapy to optimise the treatment and management of patients with cancer.

Introduction

In the past 80 years, scientific reports have provided an extensive assessment of the mechanisms of exercise intolerance in individuals who are healthy, ageing, athletic, or who have a chronic disease.1 These reports provide sound scientific knowledge of the underlying limitations to exercise tolerance, and this information is used to guide effective exercise training and rehabilitation programmes to improve clinical outcomes. Exercise intolerance has received comparably little attention in individuals diagnosed with cancer. The prevailing dogma was that unlike other chronic diseases, the pathophysiology of most cancer diagnoses, other than lung cancer, does not directly impact the functional or structural integrity of the systems associated with oxygen transport and utilisation (figure 1). Given the recent increased interest in exercise therapy as a component of cancer management, it has become apparent that cancer patients have markedly reduced cardiorespiratory fitness,2 which might have implications for acute and late-occurring cancer-related toxic effects and for clinical outcome. In this Review, we discuss possible causes of exercise intolerance in patients with cancer and the effects of exercise therapy to mitigate or prevent dysfunction. We also speculate on the possible effects of exercise-regulated pathways for cancer progression and therapy efficacy.

Section snippets

Exercise tolerance in healthy individuals

The ability to deliver adequate oxygen and substrate to active skeletal muscles for ATP resynthesis is a fundamental mammalian requirement. Human beings are genetically programmed to be physically active because this phenotype had selective advantages in the preagricultural era, where the ability to hunt and gather was essential for survival.3 An individual's cardiorespiratory fitness is the efficiency with which oxygen is transported from the atmosphere into mitochondria in muscle cells.4

Age-related exercise limitation

More than 50% of all cancer diagnoses and 71% of cancer deaths are in individuals older than 65 years.14 Cardiorespiratory fitness is reduced in both women and men by around 10% per decade of life.15, 16 This decrease in fitness is caused by unfavourable changes in diastolic filling and in ventricular compliance and relaxation, and losses in systolic function, lung elastic recoil, mechanical ventilation, vascular conductance, and oxidative capacity (figure 3).17, 18 Comorbid disease adversely

Exercise and clinical outcomes

More than 70 studies have investigated the effects of structured exercise training for a wide range of psychosocial and physiological outcomes among individuals diagnosed with cancer.49, 50, 51 Exercise training is associated with improvements in quality of life, exercise capacity, physical functioning, and fatigue.50 No serious adverse events to exercise training have been reported. Preliminary evidence of a benefit for exercise for patients with cancer is promising, and more large-scale,

Conclusion

Evidence reviewed in this paper indicates that, similar to other healthy adults, patients with cancer are subject to the effects of ageing, age-related and disease-related comorbid conditions, and deconditioning that adversely affect components of the oxygen cascade and lead to reduced exercise tolerance. These normal consequences are, however, dramatically compounded by the effects of conventional and modern cancer therapies which lead to marked reductions in exercise tolerance predisposing to

Search strategy and selection criteria

References for this Review were found through a search of PubMed, Medline, Sport Discus, and Cochrane Controlled Trials Register by use of the following search terms: “exercise”, “cardiorespiratory fitness”, “exercise limitation”, “cardiopulmonary fitness”, “functional capacity”, “exercise test”, “oxygen cascade”, “oncology”, “cancer”, “surgery”, “radiation”, “chemotherapy”, “biologics”, “angiogenesis”, “hormone therapy” “metabolism”, and “small molecule inhibitors” Relevant reference

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