Date of Award

2013

Degree Type

Thesis

Degree Name

Doctor of Philosophy

School

School of Exercise and Health Sciences

Faculty

Health, Engineering and Science

First Advisor

Professor Rob Newton

Second Advisor

Professor Daniel Galvao

Third Advisor

Professor Dennis Taaffe

Abstract

A common treatment for prostate cancer, which is the most common form of cancer after skin cancer in Australian males, is androgen deprivation therapy (ADT). However, ADT is associated with an array of adverse effects including reduced bone and lean mass, loss of muscle strength, negative change in lipid profile, and increased risk of cardiovascular disease (CVD) as well as diabetes, all of which can compromise physical function and quality of life. Physical exercise has been suggested as a key lifestyle intervention for this group of cancer patients as it has enormous potential to limit and even reverse the effects of such treatment toxicities. This thesis is comprised of a review of the literature and three experimental chapters examining the effects of androgen deprivation therapy (ADT) and the role of exercise in ADT treated prostate cancer patients. The review of literature provides a background to cancer, in particular prostate cancer and the commonly reported side effects of treatment. The review identified gaps in the literature that highlighted the need for well controlled and longer term experimental studies to: 1) investigate the impact of androgen deprivation therapy duration on cardiovascular and metabolic outcomes, and 2) investigate the effects of a long term exercise intervention in reversing cardiovascular risk factors and unfavourable alterations in the metabolic profile.

Study 1 examined the feasibility and safety of a maximal treadmill exercise test in ADT treated prostate cancer patients as this was a key assessment of physiological response to the exercise intervention. One hundred and twelve prostate cancer patients undergoing ADT took part in a physician supervised multistage maximal stress test (Bruce protocol). Of these men, 85% were able to meet the criteria for the attainment of VO2max whilst three positive tests (3.2%) were observed. The three participants who recorded a positive stress test were sent for further examination and subsequently cleared of any serious issues. Apart from the relatively low VO2max (10-15th percentile), compared to healthy age matched controls, the cardiovascular response to exercise is similar in this cancer population. Maximal exercise testing in this population was demonstrated to be feasible and safe providing a direct assessment of VO2max whilst treatment duration did not appear to influence the cardiovascular responses to exercise.

Study 2 was a cross-sectional design comparing chronic versus acute ADT treated patients to examine if therapy time exposure leads to additional risk factors for CVD and metabolic toxicities in prostate cancer patients. One hundred and seven men undergoing ADT for treatment of prostate cancer were stratified into two groups, either acute (months) or chronic (>3 months) exposure. Chronic ADT exposure was associated with a 17% reduction maximal aerobic capacity (-0.4 L.min-1) and an 8% reduction in resting metabolic rate (-147 kcal/24hr). The chronically exposed group also exhibited 8-22% lower maximal strength values (chest press -5.9kg, seated row -3.9kg, leg press -27.5kg and leg extension -12.2 kg) and a corresponding decrement in physical function variables ranging from 9-16% (400m walk +24.9s, chair rise +2.0s, and stair climb +0.7s). Whilst not significant, there was also a trend towards a decrease in lean mass of 3.5% (-2.1kg) and an increase in fat mass of 6.5% (1.5kg) in the chronically suppressed group. ADT exposure did in fact have a negative effect on CVD risk factors as well as physical function outcomes. Whilst the exact mechanisms remain unclear as to why these cardiovascular alterations and physical function variables are further declining as treatment time progresses, it is possible that factors other than those assessed in this study, such as reduced physical activity levels, may have influenced the results.

Study 3 utilised a randomized controlled trial (RCT) study design to examine the long-term effects (6 months) of a combined aerobic and resistance training intervention in reducing or stabilizing CVD and diabetes risk factors in men receiving ADT. Participants were randomly allocated to either an exercise (EX) group (n= 50) or a control (CON) group (n= 48). The combined aerobic and resistance training program consisted of twice weekly clinic based sessions at which the participants completed 20mins of aerobic activity (70- 90% maximal intensity) and 6 resistance based exercises targeting the major upper and lower body muscle groups. In addition, participants were prescribed a home based training program consisting of 110 minutes of aerobic activity. The control group were instructed to adhere to their usual lifestyle and care routine. Body composition [lean mass 1.1% (+0.8kg), fat mass -4.2% (-1.1kg) & body fat -3.8% (-1.1kg], muscular strength [chest press 9.6% (+3.6kg), seated row 7% (+6.0kg), leg press 14.8% (+20kg) & leg extension 19.4% (+10.2kg)], muscular endurance [chest press 49.4% (+5.0 reps) & leg 49.9% (+7.7 reps)] and 400m walk [-4.8% (-13s)] significantly improved (p

This research has demonstrated that: 1) maximal cardiorespiratory exercise testing is safe and feasible in this population, 2) prolonged exposure to androgen deprivation therapy (>3 months) has a negative impact on a number of cardiovascular, metabolic and physical function outcomes, and 3) a combined aerobic and resistance training program can be safely undertaken in men undergoing ADT and results in an array of benefits for cardiovascular and metabolic outcomes as well physical function. As a result of these findings, patients prescribed ADT for the treatment of prostate cancer should be appropriately counselled as to the negative side effects commonly associated with this form of treatment and be made aware of the safety and beneficial effects an appropriately administered exercise intervention can have on reversing these adverse alterations occurring throughout the course of treatment. Further, these specifically designed exercise interventions should be commenced as soon as practically possible post prostate cancer diagnosis and continue for the course of treatment and ideally beyond.

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