Can exercise ameliorate treatment toxicity during the initial phase of testosterone deprivation in prostate cancer patients? Is this more effective than delayed rehabilitation?

BMC Cancer (Impact Factor: 3.36). 09/2012; 12(1):432. DOI: 10.1186/1471-2407-12-432
Source: PubMed


There has been substantial increase in use of androgen deprivation therapy as adjuvant management of prostate cancer. However, this leads to a range of musculoskeletal toxicities including reduced bone mass and increased skeletal fractures compounded with rapid metabolic alterations, including increased body fat, reduced lean mass, insulin resistance and negative lipoprotein profile, increased incidence of cardiovascular and metabolic morbidity, greater distress and reduced quality of life. Numerous research studies have demonstrated certain exercise prescriptions to be effective at preventing or even reversing these treatment toxicities. However, all interventions to date have been of rehabilitative intent being implemented after a minimum of 3 months since initiation of androgen deprivation, by which time considerable physical and psychological health problems have manifested. The pressing question is whether it is more efficacious to commence exercise therapy at the same time as initiating androgen deprivation, so treatment induced adverse effects can be immediately attenuated or indeed prevented.

We are proposing a multi-site randomized controlled trial with partial crossover to examine the effects of timing of exercise implementation (immediate or delayed) on preserving long-term skeletal health, reversing short- and long-term metabolic and cardiovascular risk factors, and supporting mental health in men receiving androgen deprivation therapy. 124 men who are about to initiate androgen deprivation for prostate cancer will be randomized to immediate or delayed groups. Immediate will commence a 6-month exercise program within 7–10 days of their first dose. Delayed will receive usual care for 6 months and then commence the exercise program for 6 months (partial cross-over). Immediate will be free to adopt the lifestyle of their choosing following the initial 6-month intervention. Measurements for primary and secondary endpoints will take place at baseline, 6 months and 12 months.

This project is unique as it explores a fundamental question of when exercise implementation will be of most benefit and addresses both physical and psychological consequences of androgen deprivation initiation. The final outcome may be adjunct treatment which will reduce if not prevent the toxicities of androgen deprivation, ultimately resulting in reduced morbidity and mortality for men with prostate cancer.

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    • "A series of standard tests will be used to assess physical function: 1) 400-m walk (aerobic capacity), 2) one repetition maximum in the leg press and chest press (muscular strength), 3) repeated chair rise (muscular power), 4) usual and fast pace 6-m walk (ambulation), and 5) backwards tandem 6-m walk (balance) [20,22,57]. Physical activity levels will be assessed objectively over a 7-day period using a validated, reliable tri-axial accelerometer activity monitor (ActiGraph GT3X+) [58]. "
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    ABSTRACT: Despite being a critical survivorship care issue, there is a clear gap in current knowledge of the optimal treatment of sexual dysfunction in men with prostate cancer. There is sound theoretical rationale and emerging evidence that exercise may be an innovative therapy to counteract sexual dysfunction in men with prostate cancer. Furthermore, despite the multidimensional aetiology of sexual dysfunction, there is a paucity of research investigating the efficacy of integrated treatment models. Therefore, the purpose of this study is to: 1) examine the efficacy of exercise as a therapy to aid in the management of sexual dysfunction in men with prostate cancer; 2) determine if combining exercise and brief psychosexual intervention results in more pronounced improvements in sexual health; and 3) assess if any benefit of exercise and psychosexual intervention on sexual dysfunction is sustained long term.Methods/design: A three-arm, multi-site randomised controlled trial involving 240 prostate cancer survivors will be implemented. Participants will be randomised to: 1) 'Exercise' intervention; 2) 'Exercise + Psychosexual' intervention; or 3) 'Usual Care'. The Exercise group will receive a 6-month, group based, supervised resistance and aerobic exercise intervention. The Exercise + Psychosexual group will receive the same exercise intervention plus a brief psychosexual self-management intervention that addresses psychological and sexual well-being. The Usual Care group will maintain standard care for 6 months. Measurements for primary and secondary endpoints will take place at baseline, 6 months (post-intervention) and 1 year follow-up. The primary endpoint is sexual health and secondary endpoints include key factors associated with sexual health in men with prostate cancer. Sexual dysfunction is one of the most prevalent and distressing consequences of prostate cancer. Despite this, very little is known about the management of sexual dysfunction and current health care services do not adequately meet sexual health needs of survivors. This project will examine the potential role of exercise in the management of sexual dysfunction and evaluate a potential best-practice management approach by integrating pharmacological, physiological and psychological treatment modalities to address the complex and multifaceted aetiology of sexual dysfunction following cancer.Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12613001179729.
    BMC Cancer 03/2014; 14(1):199. DOI:10.1186/1471-2407-14-199 · 3.36 Impact Factor
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    • "All named mediators seem to be involved in tumor growth and disease progression. Additionally these cytokines and hormones can be influenced by physical activity [22-25]. "
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    ABSTRACT: Background: Exercise seems to minimize prostate cancer specific mortality risk and treatment related side effects like fatigue and incontinence. However the influence of physical activity on the immunological level remains uncertain. Even prostate cancer patients undergoing palliative treatment often have a relatively long life span compared to other cancer entities. To optimize exercise programs and their outcomes it is essential to investigate the underlying mechanisms. Further, it is important to discriminate between different exercise protocols and therapy regimes. Methods/design: The ProImmun study is a prospective multicenter patient preference randomized controlled trial investigating the influence of a 24 week endurance exercise program in 80-100 prostate cancer patients by comparing patients undergoing Antiandrogen therapy combined with exercise (AE), Antiandrogen therapy without exercise (A), Chemotherapy with exercise(CE) or Chemotherapy without exercise (C). The primary outcome of the study is a change in prostate cancer relevant cytokines and hormones (IL-6, MIF, IGF-1, Testosterone). Secondary endpoints are immune cell ratios, oxidative stress and antioxidative capacity levels, VO2 peak, fatigue and quality of life. Patients of the intervention group exercise five times per week, while two sessions are supervised. During the supervised sessions patients (AE and CE) exercise for 33 minutes on a bicycle ergometer at 70-75% of their VO2 peak. To assess long term effects and sustainability of the intervention two follow-up assessments are arranged 12 and 18 month after the intervention. Discussion: The ProImmun study is the first trial which primarily investigates immunological effects of a six month endurance exercise program in prostate cancer patients during palliative care. Separating patients treated with Antiandrogen therapy from those who are additionally treated with Chemotherapy might allow a more specific view on the influence of endurance training interventions and the impact of different therapy protocols on the immune function. Trial registration: German Clinical Trials Register: DRKS00004739.
    BMC Cancer 06/2013; 13(1):272. DOI:10.1186/1471-2407-13-272 · 3.36 Impact Factor
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    ABSTRACT: Cancer is a leading cause of burden of disease in Australia. The diagnosis of cancer is a major life stress with heightened psychological distress common and unmet psychological supportive care needs highly prevalent. There is a clinical imperative to provide accessible evidence-based psychosocial therapies to patients and their families in order to reduce distress and optimise psychological outcomes. A range of theoretical approaches have been proposed to guide psychological interventions in the context of cancer, including theories of stress and coping and social cognitive theories of adjustment. In addition, there is a well-established body of evidence demonstrating that psychosocial interventions improve psychological outcomes after cancer, and clinical practice guidelines for intervention to reduce distress in people affected by cancer have been developed based on this evidence. However, despite relevant theoretical models, empirical evidence, and the availability of guidelines, evidence-based psychosocial care for cancer patients is the exception rather than the norm. The answer to this problem may lie in research translation. A model for research translation is overviewed in this article with barriers to research translation discussed and a case study presented. Finally, recommendations for how health psychology can contribute to psycho-oncology research and practice are proposed.
    Australian Psychologist 02/2014; 49(2). DOI:10.1111/ap.12044 · 0.61 Impact Factor
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