Long-Term Antitumor Activity and Safety of Enzalutamide Monotherapy in Hormone Naïve Prostate Cancer: 3-Year Open Label Followup Results.

PURPOSE: A phase 2 study of enzalutamide monotherapy in patients with hormone naïve prostate cancer demonstrated high prostate specific antigen response rates at 25 weeks, 1 year and 2 years with minimal effects on total body bone mineral density and favorable safety. In this followup analysis we evaluated enzalutamide antitumor activity and safety at 3 years. MATERIALS AND METHODS: In a single arm analysis 67 patients with hormone naïve prostate cancer and noncastrate testosterone (230 ng/dl or greater) received enzalutamide 160 mg per day orally until disease progression or unacceptable toxicity. The primary end point was the prostate specific antigen response (80% or greater decline from baseline). RESULTS: No patients discontinued treatment during year 3. Of 42 patients with prostate specific antigen assessments at 3 years 38 (90.5%, 95% CI 77.4-97.3) maintained a prostate specific antigen response. Of 26 patients with metastases at baseline 17 (65.4%) had a complete or partial response as the best overall response during 3 years. In patients who completed the 3-year visit minimal mean changes from baseline were observed in total body bone mineral density or bone mineral density of the femoral neck, trochanter, spine L1-L4 or forearm (range -2.7% to -0.1%). At 3 years total body fat had increased a mean of 16.5%, total lean body mass had decreased a mean of -6.5% and global health status had minimally decreased from baseline. Common adverse events were gynecomastia, fatigue, hot flush and nipple pain. CONCLUSIONS: Enzalutamide antitumor activity was maintained in patients with hormone naïve prostate cancer at 3 years. Overall bone mineral density, global health status and safety results were similar to those at 2 years.

Management of BPH then 2000 and now 2016 - From BPH to BPO.

The diagnosis and treatment of benign prostatic obstruction (BPO) is based on a number of well-known lower urinary tract symptoms (LUTS) feared by all ageing males with functional testes. The ascent of modern urology turned this disease from lethal into an annoying but treatable health problem in the previous century. We are able to relieve the great majority of patients from their bothersome symptoms to a respectable quality of life by medication or removal of the obstructive part of the enlarged prostate. We can be proud of some progress made in the new millennium to reach a correct diagnosis and subsequent choice of treatment aiming for quality of life and cost-efficiency for public health. Still it remains symptomatic treatment and we expect the new generation of urologists to close some gaps in our knowledge on the regulation of prostatic growth to focus on prevention and elimination of the disease in the foreseeable future.

The sociobiology of genes: the gene's eye view as a unifying behavioural-ecological framework for biological evolution.

Although classical evolutionary theory, i.e., population genetics and the Modern Synthesis, was already implicitly 'gene-centred', the organism was, in practice, still generally regarded as the individual unit of which a population is composed. The gene-centred approach to evolution only reached a logical conclusion with the advent of the gene-selectionist or gene's eye view in the 1960s and 1970s. Whereas classical evolutionary theory can only work with (genotypically represented) fitness differences between individual organisms, gene-selectionism is capable of working with fitness differences among genes within the same organism and genome. Here, we explore the explanatory potential of 'intra-organismic' and 'intra-genomic' gene-selectionism, i.e., of a behavioural-ecological 'gene's eye view' on genetic, genomic and organismal evolution. First, we give a general outline of the framework and how it complements the-to some extent-still 'organism-centred' approach of classical evolutionary theory. Secondly, we give a more in-depth assessment of its explanatory potential for biological evolution, i.e., for Darwin's 'common descent with modification' or, more specifically, for 'historical continuity or homology with modular evolutionary change' as it has been studied by evolutionary developmental biology (evo-devo) during the last few decades. In contrast with classical evolutionary theory, evo-devo focuses on 'within-organism' developmental processes. Given the capacity of gene-selectionism to adopt an intra-organismal gene's eye view, we outline the relevance of the latter model for evo-devo. Overall, we aim for the conceptual integration between the gene's eye view on the one hand, and more organism-centred evolutionary models (both classical evolutionary theory and evo-devo) on the other.

Future of keeping pet reptiles and amphibians: towards integrating animal welfare, human health and environmental sustainability.

The keeping of exotic pets is currently under debate and governments of several countries are increasingly exploring the regulation, or even the banning, of exotic pet keeping. Major concerns are issues of public health and safety, animal welfare and biodiversity conservation. The keeping of reptiles and amphibians in captivity encompasses all the potential issues identified with keeping exotic pets, and many of those relating to traditional domestic pets. Within the context of risks posed by pets in general, the authors argue for the responsible and sustainable keeping of reptile and amphibian pets by private persons, based on scientific evidence and on the authors' own expertise (veterinary medicine, captive husbandry, conservation biology).

Phase III randomised chemoprevention study with selenium on the recurrence of non-invasive urothelial carcinoma. The SELEnium and BLAdder cancer Trial.

BACKGROUND: In Belgium, bladder cancer (BC) is the fifth most common cancer in men. The per-patient lifetime cost is high. Previous epidemiological studies have consistently reported that selenium concentrations were inversely associated with the risk of BC. We therefore hypothesised that selenium may be suitable for chemoprevention of recurrence of BC. METHOD: The Selenium and Bladder Cancer Trial (SELEBLAT) was an academic phase III placebo-controlled, double-blind, randomised clinical trial designed to determine the effect of selenium on recurrence of non-invasive urothelial carcinoma conducted in 14 Belgian hospitals. Patients were randomly assigned by a computer program to oral selenium yeast 200 µg once a day or placebo for three years, in addition to standard care. All study personnel and participants were blinded to treatment assignment for the duration of the study. All randomised patients were included in the intention to treat (ITT) and safety analyses. Per protocol analyses (PPAs) included all patients in the study three months after start date. RESULTS: Between September 18, 2009 and April 18, 2013, 151 and 141 patients were randomised in the selenium and placebo group. Patients were followed until December 31, 2015. The ITT analysis resulted in 43 (28%; 95% CI, 0.21-0.35) and 45 (32%; 95% CI, 0.24-0.40) recurrences in the selenium and placebo group. The hazard ratio (HR) was 0.85 (95% CI, 0.56-1.29; p = 0.44) while the HR for the PPA resulted in 42 and 39 (28%; 95% CI, 0.20-0.35) recurrences in the selenium and placebo group (HR = 0.96 [95% CI, 0.62-1.48]; p = 0.93). CONCLUSION: Selenium supplementation does not lower the probability of recurrence in BC patients.

Changes in Body Image in Patients with Prostate Cancer over 2 Years of Treatment with a Gonadotropin-Releasing Hormone Analogue (Triptorelin): Results from a Belgian Non-Interventional Study.

BACKGROUND: Androgen deprivation therapy has been associated with worsened body image in prostate cancer patients. Body image and physical presentation changes were investigated in patients receiving a gonadotropin-releasing hormone analogue (triptorelin) as part of treatment for locally advanced or metastatic prostate cancer. OBJECTIVE: The aim was to evaluate the changes in self-perception of the body and to assess the relationship of these changes over a period of 2 years in men treated with triptorelin as primary therapy for advanced or locally advanced prostate cancer. METHODS: Data were collected for 2 years in accordance with routine clinical practice. Body image was assessed using the body image scale (BIS). Patient body mass index (BMI) and waist circumference were also measured. RESULTS: BIS and BMI data for both baseline and a least one post-baseline visit were available for 98 of the 145 patients enrolled. The median change in BIS score for patients assessed around 12 or 24 months after baseline and at the last observation was zero, indicating no body image deterioration in at least half of patients. Statistically significant BIS score increases were detected in assessments around 6, 12 and 18 months, but not after 2 years, indicating some patients experienced body image deterioration at some point during treatment. Changes in BMI from baseline were modest and generally not statistically significant. Waist circumference increased during the study (mean ± standard deviation increase of 1.00 ± 5.01 cm at the last observation). Positive correlations were determined between increases in BIS score and both BMI and waist circumference (r = 0.235 and 0.267, respectively; p = 0.020 and 0.008) at the last observation for all patients, as well as during the second year of the study. CONCLUSIONS: Most patients did not experience clinically meaningful worsening of body image perception during the study. BMI and waist circumference had a modest impact on body image during study year 2.

Urinary incontinence in patients with cystic fibrosis.

OBJECTIVE: Owing to evolution in treatment, the average life expectancy of patients with cystic fibrosis (CF) has increased. This has been followed by an increase in urological complications such as urinary incontinence. As stress incontinence occurs during exercise, it may have a negative effect on the implementation of respiratory physiotherapy. The purpose of this study is to determine the prevalence of urinary incontinence and its effect on the quality of life and physiotherapy in a population with CF. MATERIALS AND METHODS: Questionnaires were used to determine the prevalence of incontinence in patients of the Cystic Fibrosis Clinic of the University Hospital in Brussels. Two different surveys were used, depending on the age of the patients (< 12 or ≥ 12 years). The different characteristics of incontinence were emphasized. RESULTS: Questionnaires were completed by 122 participants aged 6-59 years, showing an overall prevalence of 27% for urinary incontinence. Mainly adults reported urinary incontinence, with a prevalence of 11% in men and 68% in women aged 12 and above. The amount of urinary leakage was usually only a few drops and it was mainly triggered by coughing. Many of the participants had never mentioned this symptom to anyone. CONCLUSIONS: Doctors' and physical therapists' attention should be drawn to the fact that urinary incontinence is part of the complication spectrum of CF. A quarter of the study population refrained from coughing up phlegm and from physiotherapy. It is important to actively question and inform about this problem, to enable its detection and treatment.

Fatal attraction: the intuitive appeal of GMO opposition.

Public opposition to genetically modified organisms (GMOs) remains strong. By contrast, studies demonstrate again and again that GM crops make a valuable contribution to the development of a sustainable type of agriculture. The discrepancy between public opinion and the scientific evidence requires an explanation. We argue that intuitive expectations about the world render the human mind vulnerable to particular misrepresentations of GMOs. We explain how the involvement of particular intuitions accounts for the popularity, persistence, and typical features of GM opposition and tackle possible objections to our approach. To conclude, we discuss the implications for science education, science communication, and the environmental movement.

Long-term Efficacy and Safety of Enzalutamide Monotherapy in Hormone-naïve Prostate Cancer: 1- and 2-Year Open-label Follow-up Results.

BACKGROUND: Enzalutamide is an androgen receptor inhibitor with a demonstrated overall survival benefit in metastatic castration-resistant prostate cancer. A phase 2 study of enzalutamide monotherapy in patients with hormone-naïve prostate cancer (HNPC) showed a high response rate for the prespecified primary endpoint (ie, prostate-specific antigen [PSA] response at week 25), regardless of metastases at baseline, and favorable tolerability. OBJECTIVE: To determine the long-term efficacy and safety of enzalutamide monotherapy at 1 and 2 yr. DESIGN, SETTING, AND PARTICIPANTS: Open-label, single-arm study in patients with HNPC and noncastrate testosterone (≥230 ng/dl). INTERVENTION: Oral enzalutamide 160mg/d until disease progression or unacceptable toxicity. OUTCOME MEASUREMENTS AND ANALYSIS: PSA response (≥80% decline from baseline) assessed at 1 yr (49 wk) and 2 yr (97 wk). RESULTS AND LIMITATIONS: The median (range) age was 73 (48-86) yr and 26 patients (39%) presented with metastases at study entry. Of 67 patients enrolled, 45 (67%) remained on enzalutamide at week 97. For patients remaining on therapy, the PSA response rate at week 97 was 100% (95% confidence interval 92-100%). Of 26 patients with metastases at baseline, 13 (50%) had a complete and four (15.4%) had a partial response as best overall tumor response up to 97 wk on treatment. There was overall maintenance of total-body bone mineral density (BMD) and moderate changes in lean and fat body mass at 49 and 97 wk. The most common adverse events were gynecomastia, nipple pain, fatigue, and hot flushes. The study limitations include lack of a control group and of endocrine, glycemic, and lipid data at 97 wk. CONCLUSIONS: Long-term enzalutamide monotherapy in men with noncastrate HNPC is associated with large sustained reductions in PSA, signals indicating a favorable tumor response, and favorable safety/tolerability profile, with relatively small negative effects on total-body BMD. PATIENT SUMMARY: In this long-term follow-up of the efficacy and safety of enzalutamide monotherapy in patients with hormone-naïve prostate cancer, enzalutamide maintained long-term reductions in prostate-specific antigen, with a minimal impact on total-body bone mineral density. TRIAL REGISTRATION: NCT01302041.

Efficacy and tolerability of 1- and 3-month leuprorelin acetate depot formulations (Eligard(®)/Depo-Eligard(®)) for advanced prostate cancer in daily practice: a Belgian prospective non-interventional study.

INTRODUCTION: The 1-, 3- and 6- month biodegradable polymer matrix depot formulations of leuprorelin acetate (Eligard(®)/Depo-Eligard(®), Astellas Pharma Inc/BV) were shown to reduce testosterone and prostate-specific antigen levels and to be well tolerated in patients with advanced prostate cancer in several clinical trials. This study aimed at evaluating the efficacy, safety and tolerability of the 1- and 3-month leuprorelin acetate depot formulations in daily clinical practice. MATERIAL AND METHODS: A prospective, open-label, non-interventional, phase IV study (MANTA) was conducted in 243 Belgian prostate cancer patients who had been prescribed the 1-month (7.5 mg) or 3-month (22.5 mg) leuprorelin acetate depot formulation. Patients were followed for at least 3 months. RESULTS: Median serum prostate-specific antigen levels were reduced by 95% from 12.0 ng/ml at baseline to 0.60 ng/ml after a median follow-up time of 132 days, while median testosterone levels were reduced by 94% from 360 ng/dl to 20 ng/dl. Partial or complete treatment response was observed in 83% of patients at the final visit (according to the physician's assessment). Ninety-two patients (37.86%) experienced treatment-emergent adverse events, with injection site-related reactions, hot flushes and tumor flare being the most common ones. Overall safety and tolerability of the leuprorelin acetate depot formulation were rated as good or excellent by 90% of physicians. CONCLUSIONS: These data are consistent with efficacy and tolerability results from clinical trials. They confirm that the 1- and 3-month leuprorelin acetate depot formulations are well tolerated and reliably lower serum prostate-specific antigen and testosterone levels in routine clinical practice.

Enzalutamide monotherapy in hormone-naive prostate cancer: primary analysis of an open-label, single-arm, phase 2 study.

BACKGROUND: The androgen receptor inhibitor enzalutamide is approved for the treatment of metastatic castration-resistant prostate cancer that has progressed on docetaxel. Our aim was to assess the activity and safety of enzalutamide monotherapy in men with hormone-naive prostate cancer. METHODS: This trial is an ongoing open-label, single-arm, phase 2 study, done across 12 European sites. Men aged over 18 years, with hormone-naive prostate cancer for whom hormone therapy was indicated, and who had non-castration levels of testosterone and prostate-specific antigen (PSA) of 2 ng/mL or greater at screening, and an Eastern Cooperative Oncology Group score of 0, received oral enzalutamide 160 mg/day. The primary outcome was the proportion of patients with an 80% or greater decline in PSA at week 25. All analyses included all patients who had received at least one dose of the study drug. This study is registered with ClinicalTrials.gov, number NCT01302041. FINDINGS: 67 men were enrolled into the study. 62 patients (92.5%, 95% CI 86.2-98.8) had a decline in PSA of 80% or greater at week 25. The most commonly reported treatment-emergent adverse events up to week 25 were gynaecomastia (n=24), fatigue (n=23), nipple pain (n=13), and hot flush (n=12), all of which were of mild to moderate severity. Nine patients had a treatment-emergent adverse event of grade 3 or higher, most of which were reported in one patient each, except for pneumonia (grade 3, two patients) and hypertension (grade 3, four patients). Five patients reported serious adverse events, none of which were deemed to be treatment related. INTERPRETATION: Our findings suggest that enzalutamide monotherapy in men with hormone-naive prostate cancer of varying severity provides a level of disease suppression, and was generally well tolerated. These findings provide a rationale for further investigation of clinical response and outcomes with enzalutamide in non-castrate men with prostate cancer.

Individual differences in reproductive strategy are related to views about recreational drug use in Belgium, The Netherlands, and Japan.

Individual differences in moral views are often explained as the downstream effect of ideological commitments, such as political orientation and religiosity. Recent studies in the U.S. suggest that moral views about recreational drug use are also influenced by attitudes toward sex and that this relationship cannot be explained by ideological commitments. In this study, we investigate student samples from Belgium, The Netherlands, and Japan. We find that, in all samples, sexual attitudes are strongly related to views about recreational drug use, even after controlling for various ideological variables. We discuss our results in light of reproductive strategies as determinants of moral views.

Prostate HistoScanning: a screening tool for prostate cancer?

OBJECTIVE: To evaluate Prostate HistoScanning as a screening tool for prostate cancer in a pilot study. METHODS: During a 6-month period, 94 men with normal or suspicious digital rectal examination, normal or elevated prostate-specific antigen, or an increased prostate-specific antigen velocity were examined with Prostate HistoScanning. Based on these parameters and HistoScanning analysis, 41 men were referred for prostate biopsy under computer-aided ultrasonographic guidance. The number of random biopsy cores varied depending on the prostate volume. Targeted biopsies were taken in the case of computer-aided ultrasonographic area suspicious for malignancy. A logistic regression analysis was carried out to estimate the probability of resulting in a positive prostate biopsy based on the HistoScanning findings. RESULTS: Following a logistic regression analysis, after adjusting for age, digital rectal examination, serum prostate-specific antigen level, prostate volume and tumor lesion volume, every cancer volume increase of 1 mL estimated by HistoScanning was associated with a nearly threefold increase in the probability of resulting in a positive biopsy (odds ratio 2.9; 95% confidence interval 1.2-7.0; P-value 0.02). Prostate cancer was found in 17 of 41 men (41%). In patients with cancer, computer-aided ultrasonography-guided biopsy was 4.5-fold more likely to detect cancer than random biopsy. The prostate cancer detection rate for random biopsy and directed biopsy was 13% and 58%, respectively. HistoScanning-guided biopsy significantly decreased the number of biopsies necessary (P-value <0.0001). CONCLUSIONS: Our findings suggest that Prostate HistoScanning might be helpful for the selection of patients in whom prostate biopsies are necessary. This imaging technique can be used to direct biopsies in specific regions of the prostate with a higher cancer detection rate.

Livelihoods, power, and food insecurity: adaptation of social capital portfolios in protracted crises--case study Burundi.

The failure of food security and livelihood interventions to adapt to conflict settings remains a key challenge in humanitarian responses to protracted crises. This paper proposes a social capital analysis to address this policy gap, adding a political economy dimension on food security and conflict to the actor-based livelihood framework. A case study of three hillsides in north Burundi provides an ethnographic basis for this hypothesis. While relying on a theoretical framework in which different combinations of social capital (bonding, bridging, and linking) account for a diverse range of outcomes, the findings offer empirical insights into how social capital portfolios adapt to a protracted crisis. It is argued that these social capital adaptations have the effect of changing livelihood policies, institutions, and processes (PIPs), and clarify the impact of the distribution of power and powerlessness on food security issues. In addition, they represent a solid way of integrating political economy concerns into the livelihood framework.

Designing the selenium and bladder cancer trial (SELEBLAT), a phase lll randomized chemoprevention study with selenium on recurrence of bladder cancer in Belgium.

BACKGROUND: In Belgium, bladder cancer is the fifth most common cancer in males (5.2%) and the sixth most frequent cause of death from cancer in males (3.8%). Previous epidemiological studies have consistently reported that selenium concentrations were inversely associated with the risk of bladder cancer. This suggests that selenium may also be suitable for chemoprevention of recurrence. METHOD: The SELEBLAT study opened in September 2009 and is still recruiting all patients with non-invasive transitional cell carcinoma of the bladder on TURB operation in 15 Belgian hospitals. Recruitment progress can be monitored live at http://www.seleblat.org. Patients are randomly assigned to selenium yeast (200 µg/day) supplementation for 3 years or matching placebo, in addition to standard care. The objective is to determine the effect of selenium on the recurrence of bladder cancer. Randomization is stratified by treatment centre. A computerized algorithm randomly assigns the patients to a treatment arm. All study personnel and participants are blinded to treatment assignment for the duration of the study. DESIGN: The SELEnium and BLAdder cancer Trial (SELEBLAT) is a phase III randomized, placebo-controlled, academic, double-blind superior trial. DISCUSSION: This is the first report on a selenium randomized trial in bladder cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00729287.

Detection, localisation and characterisation of prostate cancer by prostate HistoScanning(™).

UNLABELLED: What's known on the subject? and What does the study add? Prostate cancer is one of the few solid-organ cancers in which imaging is not used in the diagnostic process. Novel functional magnetic resonance imaging techniques offer promise but may not be cost-effective. Prostate HistoScanning(™) (PHS) is an ultrasound-based tissue characterisation technique that has previously shown encouraging results in the detection of clinically significant prostate cancer. The present study reports on the open 'unblinded' phase of a European multicentre study. The prospective 'blind' phase is currently in progress and will determine the value of PHS in a robust fashion overcoming many of the biases inherent in evaluating prostate imaging. OBJECTIVE: To evaluate the ability of prostate HistoScanning(™) (PHS) an ultrasound (US)-based tissue characterization application, to detect cancer foci by correlating results with detailed radical prostatectomy (RP) histology. PATIENT AND METHODS: In all, 31 patients with organ-confined prostate cancer, diagnosed on transrectal biopsies taken using US guidance, and scheduled for RP were recruited from six European centres. Before RP three-dimensional (3D) US raw data for PHS analysis was obtained. Histology by Bostwick Laboratories (London) examined sections obtained from whole mounted glands cut every 3-4 mm. Location and volume estimation of cancer foci by PHS were undertaken using two methods; a manual method and an embedded software tool. In this report we evaluate data obtained from a planned open study phase. The second phase of the study is 'blinded', and currently in progress. RESULTS: 31 patients were eligible for this phase. Three patients were excluded from analysis due to inadequate scan acquisition and pathology violations of the standard operating procedure. One patient withdrew from the study after 3D TRUS examination. PHS detected cancer ≥ 0.20 mL in 25/27 prostates (sensitivity 93%). In all, 23 patients had an index focus ≥ 0.5 mL at pathology, of which 21 were identified as ≥ 0.5 mL by PHS using the manual method (sensitivity 91%) and 19 were correctly identified as ≥ 0.5 mL by the embedded tool (sensitivity 83%). In 27 patients, histological analysis found 32 cancerous foci ≥ 0.2 mL, located in 97 of 162 sextants. After sextant analysis, PHS showed a 90% sensitivity and 72% specificity for the localisation of lesions ≥ 0.2 mL within a sextant. CONCLUSIONS: PHS has the ability to identify and locate prostate cancer and consequently may aid in pre-treatment and pre-surgical planning. In men with a lesion identified, it has potential to enable improved targeting, allowing better risk stratification by obtaining more representative cores. However further verification from the results of the blinded phase of this study are awaited.

Cabazitaxel for the treatment of prostate cancer.

INTRODUCTION: Prostate cancer is a frequently diagnosed male cancer. In men presenting locally advanced or metastatic disease, the mainstay of treatment is hormonal suppression. Despite the castrate levels of testosterone, with time, prostate cancer gradually evolves into a castration-refractory state. Chemotherapeutic agents are able to influence the natural history of metastatic castration-resistant prostate cancer. Docetaxel is a clinically relevant, FDA-approved taxane. Today, it is the first-line chemotherapeutic agent in castration-refractory prostate cancer (CRPC). There is no standard second-line chemotherapeutic regimen. AREAS COVERED: This review provides information on the efficacy of cabazitaxel as a second-line treatment for CRPC. The medline database was searched for clinical trials on chemotherapeutical treatment options of castration-resistant prostate cancer. All available data on the efficacy of cabazitaxel are summarized. EXPERT OPINION: New treatment strategies for castration-resistant prostate cancer should primarily focus on quality of life. In this view, vaccination therapy seems promising because of the acceptable level of toxicity. However, more research is needed to prove their efficacy in the treatment of castration-resistant prostate cancer. Cabazitaxel seems to be a promising second-line therapy in CRPC.