International study into the use of intermittent hormone therapy in the treatment of carcinoma of the prostate : A meta-analysis of 1446 patients

OBJECTIVE: To review pooled phase II data to identify features of different regimens of intermittent hormone therapy (IHT), developed to reduce the morbidity of treating metastatic prostate cancer, and which carries a theoretical advantage of delaying the onset of androgen-independent prostate cancer, (AIPC) that are associated with success, highlighting features which require exploration with prospective trials to establish the best strategies for using this treatment. METHODS: Individual data were collated on 1446 patients with adequate information, from 10 phase II studies with >50 cases, identified through Pubmed. RESULTS: Univariate and multivariate Cox proportional hazard models were developed to predict treatment success with a high degree of statistical success. The prostate-specific antigen (PSA) nadir, the PSA threshold to restart treatment, and medication type and duration, were important predictors of outcome. CONCLUSIONS: The duration of biochemical remission after a period of HT is a durable early indicator of how rapidly AIPC and death will occur, and will make a useful endpoint in future trials to investigate the best ways to use IHT based on the important treatment cycling variables described above. Patients spent a mean of 39% of the time off treatment. The initial PSA level and PSA nadir allow the identification of patients with prostate cancer in whom it might be possible to avoid radical therapy.Peer reviewe

Whole body vibration exposure on markers of bone turnover, body composition, and physical functioning in breast cancer patients receiving aromatase inhibitor therapy: A randomized controlled trial

Introduction: Women with breast cancer are often prescribed aromatase inhibitors, which can cause rapid loss of bone mass leading to significant potential for morbidity. Vibration training has been shown to be helpful in reducing bone turnover in postmenopausal women without cancer. Aim: To examine the effect of vibration stimulus on markers of bone turnover in breast cancer patients receiving aromatase inhibitors. Methods: Thirty-one breast cancer survivors undergoing treatment with aromatase inhibitors were randomized to vibration stimulus (n = 14) or usual care control (n = 17). Low-frequency and low-magnitude vibration stimulus (27-32 Hz, 0.3g) was delivered in supervised sessions via standing on a vibration platform for 20 minutes, 3 times per week for 12 weeks. The primary outcome was blood markers of bone resorption (serum N-telopeptide X/creatine) and formation (serum type 1 procollagen N-terminal propeptide; P1NP). Other study outcomes body composition as well as measures of physical functioning. Outcomes were compared between groups using analysis of covariance adjusted for baseline values as well as time on aromatase inhibitors. Outcomes: On average, participants were 61.5 years old and overweight (ie, body mass index = 28.5 kg/m2). Following vibration training, there was no significant difference between groups for bone resorption (adjusted group difference 0.5, P = .929) or formation (adjusted group difference 5.3, P = .286). There were also no changes in any measure of physical functioning body composition. Conclusions: Short-term low-magnitude vibration stimulus does not appear to be useful for reducing markers of bone turnover secondary to aromatase inhibitors in breast cancer patients; nor is it useful in improving physical function or symptoms. However, further investigations with larger samples and higher doses of vibration are warranted. Trial Registration: Australian and New Zealand Clinical Trials Registry (ACTRN12611001094965)

Feasibility and preliminary efficacy of a 10-week resistance and aerobic exercise intervention during neoadjuvant chemoradiation treatment in rectal cancer patients

Background: Neoadjuvant chemoradiation treatment (CRT) in rectal cancer patients is associated with a reduction in physical capacity, lean mass and increased fatigue. As a countermeasure to these treatment-related adverse effects, we examined the feasibility and preliminary efficacy of a 10-week exercise program during CRT. Methods: Ten rectal cancer patients (7 men, aged 27-70 years, body mass index = 26.4 ± 3.8 kg/m2) receiving CRT undertook supervised resistance and aerobic exercise twice weekly. Assessments were undertaken pre- and post-intervention for upper and lower body muscle strength by 1-RM, muscle endurance, physical performance tests, body composition by dual X-ray absorptiometry, quality of life, and fatigue. Results: There was a significant loss in appendicular skeletal muscle (−1.1 kg, P =.012), and fat mass (−0.8 kg, P =.029) following CRT. Despite the loss in skeletal muscle, leg press (P =.030) and leg extension (P =.046) strength improved by 27.2% and 22.7%, respectively, and leg press endurance by 76.7% (P =.007). Changes in strength were accompanied by improved performance (P\u3c .05) in 6-m fast walking speed (6.9%) and dynamic balance as determined by the 6-m backwards walk (15.5%). There was minimal change in quality of life and fatigue, and no adverse events related to training. Conclusions: Exercise during neoadjuvant CRT appears to be feasible and well tolerated in rectal cancer patients and may enhance physical function while minimizing adverse changes in body composition and cancer-related fatigue. These initial findings need to be confirmed in randomized controlled trials

Multimodal exercise in older patients with advanced pancreatic cancer undergoing first-line chemotherapy: A case series examining feasibility and preliminary efficacy

Purpose. Exercise is emerging as an adjunct therapy to cancer treatment; however, its role in older patients with advanced pancreatic cancer undergoing first-line chemotherapy is unclear. The aim of this study was to primarily provide evidence on feasibility with an exploratory examination of the initial efficacy of exercise in this clinical setting. Materials and Methods. Six patients aged 60–75 years with de novo or recurrent advanced pancreatic cancer undergoing first-line chemotherapy consented to participate in twice-weekly exercise that included resistance and aerobic training and boxing-related activities for up to 12 weeks. Patients were monitored for attendance, adherence, and adverse events. Body composition, muscle strength, functional ability, patient-reported outcome measures, and patient-reported experience measures were assessed at baseline and/or postintervention. Results. Of the 6 patients, 1 withdrew after baseline testing and 5 attended 42%–95% of planned sessions and adhered to 28%–83% of the prescribed exercise. There were no serious exercise-emergent adverse events. All 5 patients increased or maintained lean mass (0.1%–4.4%) and 4 reduced fat mass (−0.4%–−8.6%). Improvements were observed in 4 or all 5 patients for muscle strength (7.1%–75%), 5 times sit-to-stand (1.3%–21.4%), 6-m backward walk (16.5%–35.8%), and patient-reported outcomes. Furthermore, all patients perceived exercise as very helpful in managing their cancer and expressed a strong willingness to continue exercise in the future. Conclusion. A multimodal exercise program appears feasible with potential physical and psychological benefits for older patients with advanced pancreatic cancer undergoing first-line chemotherapy. Further research including a larger sample size is warranted

Feasibility and preliminary efficacy of a 10-week resistance and aerobic exercise intervention during neoadjuvant chemoradiation treatment in rectal cancer patients

Background: Neoadjuvant chemoradiation treatment (CRT) in rectal cancer patients is associated with a reduction in physical capacity, lean mass and increased fatigue. As a countermeasure to these treatment-related adverse effects, we examined the feasibility and preliminary efficacy of a 10-week exercise program during CRT. Methods: Ten rectal cancer patients (7 men, aged 27-70 years, body mass index = 26.4 ± 3.8 kg/m2) receiving CRT undertook supervised resistance and aerobic exercise twice weekly. Assessments were undertaken pre- and post-intervention for upper and lower body muscle strength by 1-RM, muscle endurance, physical performance tests, body composition by dual X-ray absorptiometry, quality of life, and fatigue. Results: There was a significant loss in appendicular skeletal muscle (−1.1 kg, P =.012), and fat mass (−0.8 kg, P =.029) following CRT. Despite the loss in skeletal muscle, leg press (P =.030) and leg extension (P =.046) strength improved by 27.2% and 22.7%, respectively, and leg press endurance by 76.7% (P =.007). Changes in strength were accompanied by improved performance (

Effects of exercise during radiotherapy on physical function and treatment-related side effects in men with prostate cancer: A systematic review and meta-analysis

Purpose Radiation therapy is a commonly used treatment for prostate cancer; however, the side effects may negatively affect quality of life and cause patients to be less physically active. Although exercise has been shown to mitigate radiation therapy–related fatigue in men with prostate cancer during radiation therapy, other adverse effects of treatment such as physical deconditioning, urinary symptoms, or sexual dysfunction have not been systematically reviewed in this patient population. Thus, the purpose of this review was to investigate the effect of exercise on physical function and treatment-related side effects in men with prostate cancer undergoing radiation therapy. Methods A systematic literature search was conducted in the PubMed, Embase, CINAHL Plus, SPORTDiscus, and Web of Science databases in December 2020. Included studies were randomized controlled trials examining the effects of aerobic and/or resistance exercise interventions on measures of physical function and treatment-related side effects in prostate cancer patients undergoing radiation therapy. Meta-analysis was performed on outcomes that were reported in 2 or more studies. Results Seven publications from 6 randomized controlled trials involving 391 prostate cancer patients were included. Patients had stage I to IV cancer with a Gleason score of ≤ 6 to 10. Exercise resulted in consistent significant benefits for physical function in terms of cardiovascular fitness (standardized mean difference [SMD], 0.83; 95% confidence interval [CI], 0.31-1.36; P \u3c .01) and muscle function (SMD, 1.30; 95% CI, 0.53-2.07; P \u3c .01). Furthermore, there was a significant positive effect of exercise on urinary toxicity (SMD, –0.71; 95% CI, –1.25 to –0.18; P \u3c .01), but not on intestinal (P = .21) or hormonal toxicity (P = .41), depression (P = .45), or sleep symptoms (P = .88). Conclusion Based on the current evidence, exercise in men with prostate cancer undergoing radiation therapy improves physical function and mitigates urinary toxicity. The effect of exercise on other treatment-related side effects are less clear and require further investigation

Mechanical suppression of osteolytic bone metastases in advanced breast cancer patients: A randomised controlled study protocol evaluating safety, feasibility and preliminary efficacy of exercise as a targeted medicine

Background: Skeletal metastases present a major challenge for clinicians, representing an advanced and typically incurable stage of cancer. Bone is also the most common location for metastatic breast carcinoma, with skeletal lesions identified in over 80% of patients with advanced breast cancer. Preclinical models have demonstrated the ability of mechanical stimulation to suppress tumour formation and promote skeletal preservation at bone sites with osteolytic lesions, generating modulatory interference of tumour-driven bone remodelling. Preclinical studies have also demonstrated anti-cancer effects through exercise by minimising tumour hypoxia, normalising tumour vasculature and increasing tumoural blood perfusion. This study proposes to explore the promising role of targeted exercise to suppress tumour growth while concomitantly delivering broader health benefits in patients with advanced breast cancer with osteolytic bone metastases. Methods: This single-blinded, two-armed, randomised and controlled pilot study aims to establish the safety, feasibility and efficacy of an individually tailored, modular multi-modal exercise programme incorporating spinal isometric training (targeted muscle contraction) in 40 women with advanced breast cancer and stable osteolytic spinal metastases. Participants will be randomly assigned to exercise or usual medical care. The intervention arm will receive a 3-month clinically supervised exercise programme, which if proven to be safe and efficacious will be offered to the control-arm patients following study completion. Primary endpoints (programme feasibility, safety, tolerance and adherence) and secondary endpoints (tumour morphology, serum tumour biomarkers, bone metabolism, inflammation, anthropometry, body composition, bone pain, physical function and patient-reported outcomes) will be measured at baseline and following the intervention. Discussion: Exercise medicine may positively alter tumour biology through numerous mechanical and nonmechanical mechanisms. This randomised controlled pilot trial will explore the preliminary effects of targeted exercise on tumour morphology and circulating metastatic tumour biomarkers using an osteolytic skeletal metastases model in patients with breast cancer. The study is principally aimed at establishing feasibility and safety. If proven to be safe and feasible, results from this study could have important implications for the delivery of this exercise programme to patients with advanced cancer and sclerotic skeletal metastases or with skeletal lesions present in haematological cancers (such as osteolytic lesions in multiple myeloma), for which future research is recommended. Trial registration: anzctr.org.au, ACTRN-12616001368426. Registered on 4 October 2016

Feasibility of Presurgical Exercise in Men with Prostate Cancer Undergoing Prostatectomy

Background: Prostatectomy is associated with short- and long-term morbidity, which includes attenuation of muscle function and deterioration of lean body mass. Physical function is a known predictor of morbidity and mortality, with initial evidence indicating that presurgical exercise is associated with fewer postsurgical complications and shorter hospitalization. The aim was to determine the feasibility of a supervised presurgical exercise program for prostate cancer (PCa) patients scheduled for prostatectomy. Methods: Ten men (68+6.4 years old) with localized PCa undertook a 6-week resistance and aerobic exercise program prior surgery. Training was undertaken twice weekly and patients were assessed at baseline, presurgery, and 6 weeks postsurgery. Outcome measures included muscle and physical performance, body composition, urinary incontinence and questionnaire. Results: Muscle strength increased by 7.5% to 24.3% (P \u3c .05) from baseline to presurgery but decreased to pretraining levels postsurgery, except for knee extensor strength (P =.247). There were significant improvements (P \u3c .05) in the 6-m fast walk (9.3%), 400-m walk (7.4%), and chair rise (12.3%) at presurgery. Following surgery, improvements in physical performance were maintained. There was no change in lean or fat mass prior to surgery, but lean mass declined by 2.7 kg (P =.014) following surgery. There were no adverse effects from the exercise program. Conclusions: Exercise undertaken prior to prostatectomy improved muscle and physical performance, with functional benefits maintained 6 weeks postsurgery. Presurgical exercise for PCa patients has the potential to facilitate recovery by improving physical reserve capacity, especially in men with poor muscle nd physical performance

Effect of exercise adjunct to radiation and androgen deprivation therapy on patient-reported treatment toxicity in men with prostate cancer: A secondary analysis of 2 randomized controlled trials

Purpose: Physical inactivity, in addition to clinical factors, has been associated with higher levels of late pelvic symptoms in patients with prostate cancer (PCa) after radiation therapy. The aim of this study was to investigate the effect of a structured multicomponent exercise program comprised of aerobic and resistance training as well as impact loading on the prevalence and severity of symptoms commonly resulting from androgen deprivation therapy (ADT) and pelvic radiation therapy. Methods and Materials: We performed a secondary analysis of pooled data from 2 randomized controlled trials that investigated the role of exercise on treatment-related side effects in patients with PCa receiving ADT. Patients were included in the analysis if they had undergone radiation therapy during the intervention in addition to ADT. Patient-reported quality of life and functional and symptom scales were assessed using the European Organization for Research and Treatment of Cancer QLQ-C30 and PR25 before and after 6 months of exercise or usual care (UC). Results: One-hundred and fifteen patients with PCa receiving ADT, aged 47 to 84 years, who also underwent radiation therapy were included in the analysis (exercise, n = 72; UC, n = 43). There was a significant reduction in physical functioning (P = .019) and increased fatigue (P = .007) in the control group, with no change observed in the exercise group. Similarly, there was a trend toward reduced sexual activity in the control group (P = .064), with a mean adjusted change of -7.1 points. Furthermore, the prevalence of clinically important pain at 6 months was lower in the exercise group compared with UC (18.1 vs 37.2%, P = .022). No between-group differences were found for urinary (P = .473) or hormonal treatment-related symptoms (P = .552). Conclusions: Exercise during concomitant hormone and radiation treatment for men with PCa may mitigate some adverse changes in patient-reported fatigue, physical functioning, and possibly sexual activity. The promotion and provision of exercise to counter a range of treatment-related adverse effects in patients with PCa undergoing radiation therapy and ADT should be actively encouraged

Nationwide industry-led community exercise program for men with locally advanced, relapsed, or metastatic prostate cancer on androgen-deprivation therapy

Purpose Androgen-deprivation therapy in patients with prostate cancer (PCa) is associated with considerable side effects and secondary comorbidities such as overweight/obesity and cardiovascular disease. The aim of thisstudy was to investigate the effectiveness of an industry-led, treatment-integrated, community-based exercise program on outcomes of body weight, cardiovascular health, and physical function. Patients and Methods PCa patients with locally advanced, relapsed, or metastatic disease receiving leuprorelin acetate were enrolled across multiple sites in Australia and assigned supervised group exercise undertaken weekly or biweekly (ie, 16 exercise sessions in total) for 10-18 weeks, consisting of aerobic and resistance training performed at moderate-to-vigorous intensity. Results Between 2014 and 2020, 760 participants completed the baseline and follow-up assessment. Participants were age 48-94 years, and most were either overweight (42.1%) or obese (38.1%). Program compliance was high, with 90% of participants completing all 16 exercise sessions. There was a small but significant reduction in waist circumference (–0.9 cm; 95% CI [–1.2 to –0.5]; P \u3c .001) and no change in weight or body mass index. Systolic (–3.7 mmHg; 95% CI [–4.8 to –2.6]; P \u3c .001) and diastolic (–1.7 mmHg; 95% CI [–2.3 to –1.0]; P \u3c .001) blood pressure were significantly lower after the program. Furthermore, significant improvements were seen in cardiorespiratory fitness and muscle strength (P \u3c .001). For most of the investigated outcomes, participants with poorer initial measures had the greatest benefit from participating in the program. Conclusion The community exercise program was feasible and effective in preventing weight gain, reducing blood pressure, and improving physical function in patients with PCa on androgen-deprivation therapy