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The effect of exercise training on cardiometabolic health in men with prostate cancer receiving androgen deprivation therapy: a systematic review and meta-analysis.
Bigaran, A, Zopf, E, Gardner, J, La Gerche, A, Murphy, DG, Howden, EJ, Baker, MK, Cormie, P
Prostate cancer and prostatic diseases. 2021;(1):35-48
Abstract
BACKGROUND Growing evidence suggests that men exposed to androgen deprivation therapy (ADT) have an increased risk of cardiovascular disease. While exercise has shown to attenuate some adverse effects of ADT, the effects on cardiometabolic health have not been systematically evaluated. OBJECTIVE To evaluate the effect of exercise on cardiometabolic health in men with prostate cancer (PCa) receiving ADT. METHODS A systematic literature search of MEDLINE, EMBASE, CINHAL, SCOPUS, WEB OF SCIENCE and SPORTSDICUS from database inception to April 2020 was performed. A quantitative synthesis using Cohens d effect size and a meta-analysis using random-effects models were conducted. RESULTS Overall, fourteen randomised controlled trials (RCTs) and four non-randomised studies were included. Eleven RCTs (n = 939 patients) were included in the meta-analysis. Exercise training improved the 400-m-walk test (MD -10.11 s, 95% CI [-14.34, -5.88]; p < 0·00001), diastolic blood pressure (-2.22 mmHg, [-3.82, -0.61]; p = 0.007), fasting blood glucose (-0.38 mmol/L, [-0.65, -0.11]; p = 0.006), C-reactive protein (-1.16 mg/L, [-2.11, -0.20]; p = 0.02), whole-body lean mass (0.70 kg, [0.39, 1.01]; p < 0.0001), appendicular lean mass (0.59 kg, [0.43, 0.76]; p < 0.00001), whole-body fat mass (-0.67 kg, [-1.08, -0.27]; p = 0.001), whole-body fat percentage (-0.79%, [-1.16, -0.42]; p < 0.0001), and trunk fat mass (-0.49 kg, [-0.87, -0.12]; p = 0.01), compared to usual care. No significant effects on systolic blood pressure or blood lipid metabolism were detected. CONCLUSIONS In a small subset of evaluated studies, exercise may favourably improve some but not all markers of cardiometabolic health. Future exercise intervention trials with cardiometabolic outcomes as primary endpoints are needed to confirm these initial findings.
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Taxane-containing regimens for metastatic breast cancer.
Ghersi, D, Willson, ML, Chan, MM, Simes, J, Donoghue, E, Wilcken, N
The Cochrane database of systematic reviews. 2015;(6):CD003366
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Abstract
BACKGROUND It is generally accepted that taxanes are among the most active chemotherapy agents in the management of metastatic breast cancer. This is an update of a Cochrane review first published in 2003. OBJECTIVES The objective of this review was to compare taxane-containing chemotherapy regimens with regimens not containing a taxane in the management of women with metastatic breast cancer. SEARCH METHODS In this review update, we searched the Cochrane Breast Cancer Group Specialised Register, MEDLINE, EMBASE, the World Health Organization's International Clinical Trials Registry Platform (WHO ICTRP), and ClinicalTrials.gov on 14 February 2013 using keywords such as 'advanced breast cancer' and 'chemotherapy'. We searched reference lists of articles, contacted study authors, and did not apply any language restrictions. SELECTION CRITERIA Randomised controlled trials comparing taxane-containing chemotherapy regimens to regimens without taxanes in women with metastatic breast cancer. We included published and unpublished studies. DATA COLLECTION AND ANALYSIS Two review authors independently assessed trial quality and extracted data. We derived hazard ratios (HRs) for overall survival, time to progression, and time to treatment failure where possible, and used a fixed-effect model for meta-analysis. We represented objective tumour response rates and toxicity as risk ratios (RRs). We extracted quality of life data where present. MAIN RESULTS This review included 28 studies. The updated analysis included 6871 randomised women, while the original review had 3643 women. Of the 28 included studies, we considered 19 studies to be at low risk of bias overall; however, some studies failed to report details on allocation concealment and methods of outcome assessment for those outcomes that are more likely to be influenced by a lack of blinding (for example tumour response rate). Studies varied in the taxane-containing chemotherapy backbone, and the comparator arms and were categorised into three groups: Regimen A plus taxane versus Regimen A (2 studies); Regimen A plus taxane versus Regimen B (14 studies); and single-agent taxane versus Regimen C (13 studies). Thirteen studies used paclitaxel, 14 studies used docetaxel, and 1 study allowed the investigator to decide on the type of taxane; the majority of studies delivered a taxane every 3 weeks. Twenty studies administered taxanes as first-line treatment, and 21 studies involved anthracycline naïve women in the metastatic setting. The combined HR for overall survival and time to progression favoured the taxane-containing regimens (HR 0.93, 95% confidence interval (CI) 0.88 to 0.99, P = 0.002, deaths = 4477; and HR 0.92, 95% CI 0.87 to 0.97, P = 0.002, estimated 5122 events, respectively) with moderate to substantial heterogeneity across trials. If the analyses were restricted to studies of first-line chemotherapy, this effect persisted for overall survival (HR 0.93, 95% CI 0.87 to 0.99, P = 0.03) but not for time to progression (HR 0.96, 95% CI 0.90 to 1.02, P = 0.22). Tumour response rates appeared to be better with taxane-containing chemotherapy in assessable women (RR 1.20, 95% CI 1.14 to 1.27, P < 0.00001) with substantial heterogeneity across studies. Taxanes were associated with an increased risk of neurotoxicity (RR 4.84, 95% CI 3.18 to 7.35, P < 0.00001, 24 studies) and hair loss (RR 2.37, 95% CI 1.45 to 3.87, P = 0.0006, 11 studies) but less nausea/vomiting compared to non-taxane-containing regimens (RR 0.62, 95% CI 0.46 to 0.83, P = 0.001, 26 studies). Leukopaenia and treatment-related death did not differ between the two groups (RR 1.07, 95% CI 0.97 to 1.17, P = 0.16, 28 studies; and RR 1.00, 95% CI 0.63 to 1.57, P = 0.99, 23 studies, respectively). For quality of life measures, none of the individual studies reported a difference in overall or any of quality of life subscales between taxane-containing and non-taxane chemotherapy regimens. AUTHORS' CONCLUSIONS Taxane-containing regimens appear to improve overall survival, time to progression, and tumour response rate in women with metastatic breast cancer. Taxanes are also associated with an increased risk of neurotoxicity but less nausea and vomiting compared to non-taxane-containing regimens. The considerable heterogeneity encountered across studies probably reflects the varying efficacy of the comparator regimens used in these studies and indicates that taxane-containing regimens are more effective than some, but not all, non-taxane-containing regimens.
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Prevalence of osteoporosis in prostate cancer survivors: a meta-analysis.
Lassemillante, AC, Doi, SA, Hooper, JD, Prins, JB, Wright, OR
Endocrine. 2014;(3):370-81
Abstract
Androgen deprivation therapy (ADT), which is used in the treatment of prostate cancer (PCa), is associated with increased morbidity. Severe bone loss is a major consequence of androgen ablation and with an increasing number of patients undergoing this treatment, the incidence of osteoporosis and fractures can be expected to increase with a significant impact on healthcare. To evaluate the prevalence of osteoporosis, we conducted a review of the literature on bone health in men with PCa undergoing ADT. A meta-analysis was conducted using the quality effects model, and sources of heterogeneity were further explored by consideration of discordant effect sizes of included studies in the meta-analysis and examining reasons thereof. Our analyses indicate that the prevalence of osteoporosis varies between 9 and 53 % with this variation partially explained by treatment duration, disease stage, ethnicity and site of osteoporosis measurement. While it is well known that a rapid decline in bone health amongst men with PCa on ADT occurs, this meta-analysis documents the high prevalence of osteoporosis in this population and reinforces the need of preventative approaches as part of usual care of PCa patients.
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Effects of toremifene versus tamoxifen on breast cancer patients: a meta-analysis.
Chi, F, Wu, R, Zeng, Y, Xing, R, Liu, Y, Xu, Z
Breast cancer (Tokyo, Japan). 2013;(2):111-22
Abstract
Toremifene and tamoxifen are both selective estrogen receptor modulators used in the treatment of breast cancer patients. Therefore, we carried out a meta-analysis to achieve a more precise evaluation of the effects of toremifene versus tamoxifen on breast cancer patients, including the efficacy and safety, and the effects on the uterus, lipids, and bone. Comprehensive literature searches were conducted using the electronic databases and reference lists to include randomized controlled trials (RCTs) that compared toremifene with tamoxifen for breast cancer patients. Two reviewers independently selected studies and abstracted data. Data were analyzed by Review Manager, version 5.0. Twenty-three trials (7242 patients) were included. For early stage breast cancer, toremifene was associated with higher 5-year survival rates (OR 1.25, 95 % CI 1.04, 1.50), more vaginal discharge (OR 1. 32, 95 % CI 1.01, 1.73), a greater decrease in serum triglyceride levels (SMD -1.01, 95 % CI -1.89, -0.14), a smaller decrease in LDL cholesterol levels (SMD 0.45, 95 % CI 0.07, 0.84) and in bone mineral density in Ward's triangle (SMD -0.36, 95 % CI -0.71, -0.01), and a greater increase in HDL cholesterol levels (SMD 0.43, 95 % CI 0.08, 0.77) than tamoxifen. For advanced breast cancer patients, toremifene was associated with more vaginal bleeding (OR 0.45, 95 % CI 0.26, 0.80) and a greater decrease in serum triglyceride levels (SMD -1.15, 95 % CI -1.90, -0.39) than tamoxifen. Available evidence showed that toremifene could be an alternative option to tamoxifen for both early and advanced breast cancer patients. However, the methodological quality of the included studies was low. More rigorous RCTs are needed to confirm the results of this meta-analysis in the future.
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Gonadotropin-releasing hormone agonist in laparoscopic myomectomy: systematic review and meta-analysis of randomized controlled trials.
Chen, I, Motan, T, Kiddoo, D
Journal of minimally invasive gynecology. 2011;(3):303-9
Abstract
A systematic review and meta-analysis of randomized controlled trials was performed to estimate the effects on surgical outcomes of pretreatment with gonadotropin-releasing hormone (GnRH) agonist before laparoscopic myomectomy. The electronic bibliographic databases MEDLINE, EMBASE, Web of Knowledge, Scopus, and Cochrane Library, and reference lists from relevant articles were searched for English-language publications describing randomized controlled trials of GnRH agonist pretreatment vs placebo or no treatment before laparoscopic myomectomy. Three studies including 168 participants were identified. Pretreatment with GnRH agonist did not reduce operative time; however, intraoperative blood loss was statistically lowered (mean difference, 60 mL; 95% confidence interval [CI], 39-82). Statistical difference was also observed in postoperative hemoglobin concentration (mean difference, 1.15 g/dL; 95% CI, 0.46-1.83]) and red blood cell count (mean difference, 0.65 × 10(6) cells/mL; 95% CI, 0.16-1.14]) but not serum iron concentration. None of the patients in the studies experienced any major intraoperative or postoperative complications, and only 1 patient in each group required blood transfusion. This study does not show a difference in operative time with GnRH agonist pretreatment, which clarifies the previous conflicting reports on the effect of GnRH agonist therapy on the duration of laparoscopic myomectomy. Furthermore, despite previously reported decreased bleeding conferred by the laparoscopic approach compared with laparotomy, this meta-analysis demonstrates a further reduction in intraoperative blood loss with GnRH agonist pretreatment in patients undergoing laparoscopic myomectomy. Additional high-quality studies with appropriate power and follow-up are needed to corroborate these findings and to evaluate the treatment effects on short- and long-term outcomes such as perioperative complications and fertility.
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Prevention of breast cancer in postmenopausal women: approaches to estimating and reducing risk.
Cummings, SR, Tice, JA, Bauer, S, Browner, WS, Cuzick, J, Ziv, E, Vogel, V, Shepherd, J, Vachon, C, Smith-Bindman, R, et al
Journal of the National Cancer Institute. 2009;(6):384-98
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Abstract
BACKGROUND It is uncertain whether evidence supports routinely estimating a postmenopausal woman's risk of breast cancer and intervening to reduce risk. METHODS We systematically reviewed prospective studies about models and sex hormone levels to assess breast cancer risk and used meta-analysis with random effects models to summarize the predictive accuracy of breast density. We also reviewed prospective studies of the effects of exercise, weight management, healthy diet, moderate alcohol consumption, and fruit and vegetable intake on breast cancer risk, and used random effects models for a meta-analyses of tamoxifen and raloxifene for primary prevention of breast cancer. All studies reviewed were published before June 2008, and all statistical tests were two-sided. RESULTS Risk models that are based on demographic characteristics and medical history had modest discriminatory accuracy for estimating breast cancer risk (c-statistics range = 0.58-0.63). Breast density was strongly associated with breast cancer (relative risk [RR] = 4.03, 95% confidence interval [CI] = 3.10 to 5.26, for Breast Imaging Reporting and Data System category IV vs category I; RR = 4.20, 95% CI = 3.61 to 4.89, for >75% vs <5% of dense area), and adding breast density to models improved discriminatory accuracy (c-statistics range = 0.63-0.66). Estradiol was also associated with breast cancer (RR range = 2.0-2.9, comparing the highest vs lowest quintile of estradiol, P < .01). Most studies found that exercise, weight reduction, low-fat diet, and reduced alcohol intake were associated with a decreased risk of breast cancer. Tamoxifen and raloxifene reduced the risk of estrogen receptor-positive invasive breast cancer and invasive breast cancer overall. CONCLUSIONS Evidence from this study supports screening for breast cancer risk in all postmenopausal women by use of risk factors and breast density and considering chemoprevention for those found to be at high risk. Several lifestyle changes with the potential to prevent breast cancer should be recommended regardless of risk.
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Taxane containing regimens for metastatic breast cancer.
Ghersi, D, Wilcken, N, Simes, J, Donoghue, E
The Cochrane database of systematic reviews. 2005;(2):CD003366
Abstract
BACKGROUND It is generally accepted that taxanes are among the most active chemotherapy agents in the management of metastatic breast cancer. OBJECTIVES To identify and review the randomised evidence comparing taxane containing chemotherapy regimens with regimens not containing a taxane in the management of women with metastatic breast cancer. SEARCH STRATEGY The specialised register maintained by the Editorial Base of the Cochrane Breast Cancer Group was searched on 2nd May 2003 using the codes for "advanced breast cancer", "chemotherapy". Details of the search strategy applied by the Group to create the register, and the procedure used to code references, are described in the Group's module on the Cochrane Library. SELECTION CRITERIA Randomised trials comparing taxane-containing chemotherapy regimens with regimens not containing taxanes in women with metastatic breast cancer. DATA COLLECTION AND ANALYSIS Data were collected from published trials. Studies were assessed for eligibility and quality, and data were extracted, by two independent reviewers. Hazard ratios were derived for time-to-event outcomes where possible, and a fixed effect model was used for meta-analysis. Response rates were analysed as dichotomous variables. Toxicity and quality of life data were extracted where present. MAIN RESULTS Twenty one eligible trials were identified of which 12 have published time-to-event data and 16 have reported response data. The quality of randomisation was generally not described. An estimated 2621 deaths in 3643 randomised women demonstrate a statistically significant difference in favour of taxane-containing regimens with a HR for overall survival of 0.93 (95% CI=0.86-1.00, p=0.05) and no statistically significant heterogeneity. If the analysis is restricted to trials of firstline chemotherapy the HR changes to 0.92 and is no longer statistically significant (95% CI 0.84-1.02, p=0.11). There was also a significant difference in favour of taxanes in relation to time to progression (overall HR 0.92, 95%CI 0.85-0.99, p=0.02) and overall response in assessable women (overall OR 1.34, 95%CI 1.18-1.52, p<0.00001) however there was strong statistical evidence of heterogeneity (P<0.00001), probably reflecting the varying efficacy of the comparator regimens used in the trials. AUTHORS' CONCLUSIONS When all trials are considered, taxane-containing regimens appear to improve overall survival, time to progression and overall response in women with metastatic breast cancer. The degree of heterogeneity encountered indicates that taxane-containing regimens are more effective than some, but not all non-taxane-containing regimens.