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1.
Nutrition care guidelines for men with prostate cancer undergoing androgen deprivation therapy: do we have enough evidence?
Barnes, KA, Ball, LE, Galvão, DA, Newton, RU, Chambers, SK
Prostate cancer and prostatic diseases. 2019;(2):221-234
Abstract
BACKGROUND To review the evidence available to support clinical practice guidelines for dietary interventions aimed at mitigating the side effects of androgen deprivation therapy (ADT) in men with prostate cancer, and to identify future research priorities. METHODS An analytical model was designed to select and interpret evidence for the effect of dietary interventions on ADT side effects. Key terms identified articles that investigated dietary interventions to mitigate ADT side effects among men treated for prostate cancer. Medline, Embase, Proquest, CINAHL, Cochrane databases, and PubMed were searched from inception through June, 2018. Clinical trial registries were also searched for up-to-date study protocols. Articles were not restricted on design. Methodological quality was assessed using the mixed methods appraisal tool. RESULTS Sixteen articles met inclusion criteria, each with distinct dietary interventions. Twelve studies used interventions that combined diet with physical activity and/or medication and/or counselling. Four articles examined the effect of diet alone on ADT side effects. Of those, three articles measured changes to participants' dietary intake and influence on ADT side effects. One article showed daily caffeinated beverages improved cancer-related fatigue. Two articles showed no impact of isoflavone supplementation on hot flushes, quality of life, body mass index, or blood lipids. Dietary intake and compliance was poorly reported across all studies limiting knowledge of acceptability and feasibility for dietary interventions. Information on the nutrition care practices and views of clinicians treating men for prostate cancer is limited. No articles measured the impact of diet on long-term ADT side effects. Methodological quality of included papers ranged from weak to strong. CONCLUSIONS Current evidence for dietary interventions to mitigate ADT side effects is limited. Further investigations are warranted to explore the impact of changes in dietary intake on ADT side effects before practice guidelines can be considered.
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2.
Lipid Status During Combined Treatment in Prostate Cancer Patients.
Wolny-Rokicka, E, Tukiendorf, A, Wydmański, J, Ostrowska, M, Zembroń-Łacny, A
American journal of men's health. 2019;(5):1557988319876488
Abstract
The aim of this study was to provide a specific review of current medical literature regarding the lipid profile during prostate carcinoma (PCa) treatment. The main aim was to analyze the results presented by different authors and to find a commonality in the changes occurring during the treatment-hormonotherapy. The levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol were measured before and after the follow-up treatment. The manuscripts reviewed came from the period between 2008 and 2016. The size of the studies ranged from 16 participants to 310. The mean age was from 65 to 74 years in all studies. The Q test was used to attain all lipid parameters and to specify heterogeneity (p < .0001). After 12 months of androgen deprivation therapy (ADT), the patients had a significantly higher level serum TC and TG.
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3.
Advanced Adrenocortical Carcinoma - What to do when First-Line Therapy Fails?
Megerle, F, Kroiss, M, Hahner, S, Fassnacht, M
Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. 2019;(2-03):109-116
Abstract
Adrenocortical carcinoma is a rare endocrine malignant disease with a generally unfavorable but heterogeneous prognosis. Although even in advanced stages a subset of patients experiences long-term disease stabilisation, effective systemic treatment options are limited. Mitotane is the only approved drug and the combination of etoposide, doxorubicin and cisplatin (plus mitotane) is currently considered as treatment standard for advanced adrenocortical carcinoma based on the results of a large randomized phase III trial. However, progression-free survival is often limited and further treatment options are frequently needed. Here we summarize the current knowledge about second and third-line therapeutic modalities (local and systemic) in advanced disease. Following the recent ESE-ENSAT guidelines local therapies play an important role for these patients. Regarding systemic therapies the best data are available for gemcitabine+capecitabine or streptozotocin (both with or without mitotane). Furthermore, we introduce our own approach to patients with advanced adrenocortical carcinoma based on our experience as a large multidisciplinary clinic dedicated to the care of patients with this orphan disease.
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4.
Estrogen therapy in patients with prostate cancer: a contemporary systematic review.
Reis, LO, Zani, EL, García-Perdomo, HA
International urology and nephrology. 2018;(6):993-1003
Abstract
PURPOSE To evaluate the effectiveness and harms of DES in treating prostate cancer compared to other forms of androgen deprivation therapy (orchiectomy, LHRH agonists, and anti-androgens). METHODS We included clinical trials comparing DES with other forms of ADT (bicalutamide, flutamide, LHRH agonists, or orchiectomy) in PCa treatment. The primary outcomes were overall survival, cancer-specific survival, and progression-free survival, and secondary outcomes were cardiovascular effects. We searched in MEDLINE, EMBASE, Central, and Lilacs from inception to nowadays and saturated information for unpublished data in other sources. We performed a qualitative analysis of all included studies. It was not possible to perform meta-analysis due to low-quality trials and high heterogeneity. RESULTS Overall, 1700 references were scanned and 14 prospective randomized trials with a total of 3986 patients were included in the final analysis. Although trials showed DES as similarly effective to another forms of ADT, evidences about cardiovascular toxicity in out of date high doses have discouraged its use. In doses of 1 mg, DES has been used as secondary line PCa treatment with safety. CONCLUSIONS DES might be similarly effective to other forms of ADT on advanced PCa patients, with potential important roles. Intriguingly, the burden of severe cardiovascular toxicity is mainly related to old-fashioned doses of 5.0 and 3.0 mg. Modern PCa hormonal knowledge warrants stout high-quality prospective randomized trials in the low-dose 1 mg DES scenario.
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5.
Metabolic changes in patients with prostate cancer during androgen deprivation therapy.
Mitsuzuka, K, Arai, Y
International journal of urology : official journal of the Japanese Urological Association. 2018;(1):45-53
Abstract
Androgen deprivation therapy continues to be widely used for the treatment of prostate cancer despite the appearance of new-generation androgen-receptor targeting drugs after 2000. Androgen deprivation therapy can alleviate symptoms in patients with metastatic prostate cancer and might have a survival benefit in some patients, but it causes undesirable changes in lipid, glucose, muscle or bone metabolism. These metabolic changes could lead to new onset or worsening of diseases, such as obesity, metabolic syndrome, diabetes mellitus, cardiovascular disease, sarcopenia or fracture. Several studies examining the influence of androgen deprivation therapy in Japanese patients with prostate cancer also showed that metabolic changes, such as weight gain, dyslipidemia or fat accumulation, can occur as in patients in Western countries. Efforts to decrease these unfavorable changes and events are important. First, overuse of androgen deprivation therapy for localized or elderly prostate cancer patients should be reconsidered. Second, intermittent androgen deprivation therapy might be beneficial for selected patients who suffer from impaired quality of life as a result of continuous androgen deprivation therapy. Third, education and instruction, such as diet or exercise, to decrease metabolic changes before initiating androgen deprivation therapy is important, because metabolic changes are likely to occur in the early androgen deprivation therapy period. Fourth, routine monitoring of weight, laboratory data or bone mineral density during androgen deprivation therapy are required to avoid unfavorable events.
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6.
Tamoxifen Resistance: Emerging Molecular Targets.
Rondón-Lagos, M, Villegas, VE, Rangel, N, Sánchez, MC, Zaphiropoulos, PG
International journal of molecular sciences. 2016;(8)
Abstract
17β-Estradiol (E2) plays a pivotal role in the development and progression of breast cancer. As a result, blockade of the E2 signal through either tamoxifen (TAM) or aromatase inhibitors is an important therapeutic strategy to treat or prevent estrogen receptor (ER) positive breast cancer. However, resistance to TAM is the major obstacle in endocrine therapy. This resistance occurs either de novo or is acquired after an initial beneficial response. The underlying mechanisms for TAM resistance are probably multifactorial and remain largely unknown. Considering that breast cancer is a very heterogeneous disease and patients respond differently to treatment, the molecular analysis of TAM's biological activity could provide the necessary framework to understand the complex effects of this drug in target cells. Moreover, this could explain, at least in part, the development of resistance and indicate an optimal therapeutic option. This review highlights the implications of TAM in breast cancer as well as the role of receptors/signal pathways recently suggested to be involved in the development of TAM resistance. G protein-coupled estrogen receptor, Androgen Receptor and Hedgehog signaling pathways are emerging as novel therapeutic targets and prognostic indicators for breast cancer, based on their ability to mediate estrogenic signaling in ERα-positive or -negative breast cancer.
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7.
Medical therapy for Cushing's disease: adrenal steroidogenesis inhibitors and glucocorticoid receptor blockers.
Fleseriu, M, Petersenn, S
Pituitary. 2015;(2):245-52
Abstract
Morbidity and mortality in Cushing's disease (CD) patients are increased if patients are not appropriately treated. Surgery remains the first line therapy, however the role of medical therapy has become more prominent in patients when biochemical remission is not achieved/or recurs after surgery, while waiting effects of radiation therapy or when surgery is contraindicated. Furthermore, use of preoperative medical therapy has been also recognized. In addition to centrally acting therapies (reviewed elsewhere in this special issue), adrenal steroidogenesis inhibitors, and glucocorticoid receptor antagonists are frequently used. A PubMed search of all original articles or abstracts detailing medical therapy in CD, published within 12 months (2013-2014), were identified and pertinent data extracted. Although not prospectively studied, ketoconazole and metyrapone have been the most frequently used medical therapies. A large retrospective ketoconazole study showed that almost half of patients who continued on ketoconazole therapy achieved biochemical control and clinical improvement; however almost 20% discontinued ketoconazole due to poor tolerability. Notably, hepatotoxicity was usually mild and resolved after drug withdrawal. Etomidate remains the only drug available for intravenous use. A new potent inhibitor of both aldosterone synthase and 11β-hydroxylase, following the completion of a phase II study LCI699 is being studied in a large phase III with promising results. Mifepristone, a glucocorticoid receptor antagonist, has been approved for hyperglycemia associated with Cushing's syndrome based on the results of a prospective study where it produced in the majority of patients' significant clinical and metabolic improvement. Absence of both a biochemical marker for remission and/or diagnosis of adrenal insufficiency remain, however, a limiting factor. Patient characteristics and preference should guide the choice between different medications in the absence of clinical trials comparing any of these therapies. Despite significant progress, there is still a need for a medical therapy that is more effective and with less adverse effects for patients with CD.
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8.
Pharmacologic androgen deprivation and cardiovascular disease risk factors: a systematic review.
Romo, ML, McCrillis, AM, Brite, J, Reales, D, Dowd, JB, Schooling, CM
European journal of clinical investigation. 2015;(5):475-84
Abstract
BACKGROUND Pharmacologic androgen deprivation therapy (ADT) is widely used to treat prostate cancer. Observational studies suggest ADT is associated with cardiovascular disease and its risk factors; however, such studies may be subject to bias. Our objective was to evaluate the effect of ADT on cardiovascular disease risk factors using data from randomized controlled trials (RCTs). MATERIALS AND METHODS We conducted a systematic review using MEDLINE and MEDLINE In-Process (1950-June 2013), EMBASE (1974-June 2013) and Web of Science (1900-June 2013) for all RCTs in men with prostate cancer that compared pharmacologic ADT (i.e. use of gonadotropin-releasing hormone agonist or antagonist) with a group that did not receive ADT and reported data on cardiovascular disease risk factors including blood pressure, cholesterol, triglycerides, fibrinogen, biomarkers of insulin sensitivity, adiposity and C-reactive protein. We also searched for ongoing or unpublished trials. This study was registered at the PROSPERO International Prospective Register of Systematic Reviews (CRD42013005035). RESULTS Of the 3272 unique publications identified in our systematic review, we did not identify a single RCT that reported data on any cardiovascular disease risk factor. We were unable to locate unreported data from corresponding authors or study sponsors. CONCLUSIONS There is a lack of published, reliable evidence describing the effects of ADT on cardiovascular disease risk factors. RCTs have likely collected data on these risk factors as part of routine study monitoring; however, these data have not been published. To understand the effect of ADT on cardiovascular morbidity, these data must be made available to the scientific community.
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9.
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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10.
Peptide Receptor Radionuclide Therapy of Neuroendocrine Tumors.
Bodei, L, Kidd, M, Prasad, V, Modlin, IM
Frontiers of hormone research. 2015;:198-215
Abstract
Peptide receptor radionuclide therapy (PRRT) has been a well-accepted and effective therapeutic modality for inoperable or metastatic gastroenteropancreatic, bronchopulmonary and other neuroendocrine tumors for almost 2 decades. In general, PRRT is well tolerated with moderate toxicity in the majority of patients if the necessary precautions, appropriate dosage and coadministration of amino acids are undertaken. The two most commonly used radiopeptides, (90)Y-octreotide and (177)Lu-octreotate, produce significant objective response rates, with impact on progression-free survival and overall survival. In addition, biochemical and symptomatic responses are commonly observed. A key issue is the need to establish randomized controlled trials to standardize the treatment and facilitate comparison with other therapeutic strategies available.