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Enzalutamide

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https://www.readbyqxmd.com/read/28101887/abiraterone-or-enzalutamide-in-advanced-castration-resistant-prostate-cancer-an-indirect-comparison
#1
Akhil Chopra, Mina Georgieva, Gilberto Lopes, Chong Ming Yeo, Benjamin Haaland
BACKGROUND: To perform a comparative effectiveness analyses between enzalutamide and abiraterone acetate in both the pre-docetaxel and post-docetaxel settings based on published phase III randomized trials. METHODS: The primary measure of efficacy was the posterior probability that enzalutamide outperforms abiraterone acetate (AA) with prednisone in terms of overall survival (OS) on average. Indirect meta-estimates were generated from four randomized studies in the context of a Bayesian hierarchical model with study-specific efficacy estimates meta-analyzed on the log scale...
January 19, 2017: Prostate
https://www.readbyqxmd.com/read/28096932/contemporary-agents-in-the-management-of-metastatic-castration-resistant-prostate-cancer
#2
REVIEW
Anil Kapoor, Christopher Wu, Bobby Shayegan, Adrian P Rybak
Docetaxel-based chemotherapy has been the standard of care for metastatic castration-resistant prostate cancer (mCRPC) since 2004. Over the past few years, there has been a significant paradigm shift in the treatment landscape of this disease. A deeper understanding of prostate cancer biology, along with the development of novel agents has created hope towards treating chemotherapy-naïve and resistant disease. Following the implementation of docetaxel as the first-line therapy for mCRPC, five novel therapies have demonstrated survival benefit in mCRPC...
November 2016: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
https://www.readbyqxmd.com/read/28063845/comparative-assessment-of-efficacies-between-2%C3%A2-alternative-therapeutic-sequences-with-novel%C3%A2-androgen-receptor-axis-targeted-agents%C3%A2-in-patients-with-chemotherapy-na%C3%A3-ve-metastatic-castration-resistant-prostate-cancer
#3
Hideaki Miyake, Takuto Hara, Keita Tamura, Takayuki Sugiyama, Hiroshi Furuse, Seiichiro Ozono, Masato Fujisawa
BACKGROUND: The objective of this study was to compare the efficacies of sequential therapies with novel androgen receptor-axis-targeted (ARAT) agents in patients with docetaxel-naïve metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: This study included 108 consecutive patients with mCRPC who sequentially received abiraterone acetate (AA) and enzalutamide (Enz), in either order, without prior treatment with docetaxel. The combined prostate-specific antigen (PSA) progression-free survival (PFS) was defined as the sum of PFS1 and PFS2, representing PSA PFSs on the first and second ARAT agents, respectively...
December 22, 2016: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28063195/first-line-non-cytotoxic-therapy-in-chemotherapy-naive-patients-with-metastatic-castration-resistant-prostate-cancer-a-systematic-review-of-ten-randomised-clinical-trials
#4
REVIEW
Michiel H F Poorthuis, Robin W M Vernooij, R Jeroen A van Moorselaar, Theo M de Reijke
OBJECTIVE: To systematically evaluate all available treatment options in chemotherapy-naive patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: We systematically searched PubMed, EMBASE, and the Cochrane libraries up to March 1, 2016 for peer-reviewed publications on randomised clinical trials (RCTs). RCTs were included if progression-free survival (PFS), overall survival (OS), quality of life (QoL), or adverse events (AEs) were quantitatively evaluated...
January 6, 2017: BJU International
https://www.readbyqxmd.com/read/28059768/sox2-promotes-lineage-plasticity-and-antiandrogen-resistance-in-tp53-and-rb1-deficient-prostate-cancer
#5
Ping Mu, Zeda Zhang, Matteo Benelli, Wouter R Karthaus, Elizabeth Hoover, Chi-Chao Chen, John Wongvipat, Sheng-Yu Ku, Dong Gao, Zhen Cao, Neel Shah, Elizabeth J Adams, Wassim Abida, Philip A Watson, Davide Prandi, Chun-Hao Huang, Elisa de Stanchina, Scott W Lowe, Leigh Ellis, Himisha Beltran, Mark A Rubin, David W Goodrich, Francesca Demichelis, Charles L Sawyers
Some cancers evade targeted therapies through a mechanism known as lineage plasticity, whereby tumor cells acquire phenotypic characteristics of a cell lineage whose survival no longer depends on the drug target. We use in vitro and in vivo human prostate cancer models to show that these tumors can develop resistance to the antiandrogen drug enzalutamide by a phenotypic shift from androgen receptor (AR)-dependent luminal epithelial cells to AR-independent basal-like cells. This lineage plasticity is enabled by the loss of TP53 and RB1 function, is mediated by increased expression of the reprogramming transcription factor SOX2, and can be reversed by restoring TP53 and RB1 function or by inhibiting SOX2 expression...
January 6, 2017: Science
https://www.readbyqxmd.com/read/28049163/correction-niclosamide-inhibits-androgen-receptor-variants-expression-and-overcomes-enzalutamide-resistance-in-castration-resistant-prostate-cancer
#6
(no author information available yet)
No abstract text is available yet for this article.
January 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28045115/skeletal-related-events-significantly-impact-health-related-quality-of-life-in-metastatic-castration-resistant-prostate-cancer-data-from-prevail-and-affirm-trials
#7
F Saad, C Ivanescu, D Phung, Y Loriot, S Abhyankar, T M Beer, B Tombal, S Holmstrom
BACKGROUND: We investigated the impact of skeletal-related events (SREs) on health-related quality of life (HRQoL) in patients with metastatic castration-resistant prostate cancer (mCRPC) in phase III trials of enzalutamide versus placebo. METHODS: Patients with mCRPC experiencing at least one SRE during AFFIRM and PREVAIL were assessed for trajectory-adjusted mean change in HRQoL by first SRE using Functional Assessment of Cancer Therapy-Prostate (FACT-P; AFFIRM, three domains, and PREVAIL, nine domains) and EQ-5D (PREVAIL) instruments...
January 3, 2017: Prostate Cancer and Prostatic Diseases
https://www.readbyqxmd.com/read/28034074/does-enzalutamide-really-reduce-the-risk-of-progression-compared-with-bicalutamide-in-patients-with-castration-resistant-prostate-cancer
#8
Mehmet Ali Nahit Şendur, Bülent Yalçın
No abstract text is available yet for this article.
January 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28034067/enzalutamide-versus-bicalutamide-in-castration-resistant-prostate-cancer-the-strive-trial-there-is-no-significant-reduction-in-death-yet
#9
Jorg Michels
No abstract text is available yet for this article.
January 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28024400/cheminformatics-modeling-of-adverse-drug-responses-by-clinically-relevant-mutants-of-human-androgen-receptor
#10
Naman Paul, Lavinia A Carabet, Nada Lallous, Takeshi Yamazaki, Martin E Gleave, Paul S Rennie, Artem Cherkasov
The human androgen receptor (AR) is a ligand-activated transcription factor that plays a pivotal role in the development and progression of prostate cancer (PCa). Many forms of castration-resistant prostate cancer (CRPC) still rely on the AR for survival. Currently used antiandrogens face clinical limitations as drug resistance develops in patients over time since they all target the mutation-prone androgen binding site (ABS), where gain-of-function mutations eventually convert antagonists into agonists. With a significant number of reported distinct mutations located across the ABS, it is imperative to develop a prognostic platform which would equip clinicians with prior knowledge and actionable strategies if cases of previously unreported AR mutations are encountered...
December 27, 2016: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28011219/in-silico-selection-and-cell-based-characterization-of-selective-and-bioactive-compounds-for-androgen-dependent-prostate-cancer-cell
#11
Elisa C Santa Cruz, Adriel R Carecho, Marta E Saidel, Carlos Alberto Montanari, Andrei Leitão
Prostate cancer is one of the most prevalent types of cancer in male population. It is a hormone driven disease, especially in its initial phase. Hence, androgen deprivation therapy (ADT) is the major chemotherapeutic effort and novel AR inhibitors with improved pharmacological profiles are needed. In this report, a novel bioactive compound was selected and investigated using in silico and cell-based assays. Neq0502 compound was selective for the testosterone stimulated AR-dependent prostate cancer cell (LNCaP, GI50=22...
December 11, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28003320/post-hoc-analysis-of-japanese-patients-from-the-placebo-controlled-prevail-trial-of-enzalutamide-in-patients-with-chemotherapy-naive-metastatic-castration-resistant-prostate-cancer-updated-results
#12
Go Kimura, Takeshi Ueda
A post hoc analysis of interim results from PREVAIL, a Phase III, double-blind, placebo-controlled trial of men with metastatic castration-resistant prostate cancer, demonstrated that the treatment effects, safety and pharmacokinetics of enzalutamide in Japanese patients were generally consistent with those of the overall population. A recent longer term analysis of PREVAIL demonstrated continued benefit of enzalutamide treatment over placebo. Here, we report results from a post hoc analysis of Japanese patients enrolled in PREVAIL at the prespecified number of deaths for the final analysis...
December 20, 2016: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/27993795/gene-polymorphisms-in-antioxidant-enzymes-correlate-with-the-efficacy-of-androgen-deprivation-therapy-for-prostate-cancer-with-implications-of-oxidative-stress
#13
M Shiota, N Fujimoto, M Itsumi, A Takeuchi, J Inokuchi, K Tatsugami, A Yokomizo, S Kajioka, T Uchiumi, M Eto
BACKGROUND: Oxidative stress mitigated by antioxidant enzymes is thought to be involved in the progression to castration-resistant prostate cancer (CRPC) during androgen-deprivation therapy (ADT). This study investigated the association between genetic variations in antioxidant enzymes and the efficacy of ADT as well as its biological background. PATIENTS AND METHODS: The non-synonymous or promoter-locating polymorphisms of antioxidant enzymes were examined as well as the time to CRPC progression and overall survival in 104 and 92 patients treated with ADT for metastatic and non-metastatic prostate cancer, respectively...
December 19, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27990667/clinical-correlates-of-benefit-from-radium-223-therapy-in-metastatic-castration-resistant-prostate-cancer
#14
Ajjai Alva, Luke Nordquist, Stephanie Daignault, Saby George, Jorge Ramos, Costantine Albany, Sudhir Isharwal, Matthew McDonald, Gregory Campbell, Pongwut Danchaivijitr, Sarah Yentz, Aseem Anand, Evan Y Yu
BACKGROUND: We sought to identify potential clinical variables associated with outcomes after radium-223 therapy in routine practice. METHODS: Consecutive non-trial mCRPC patients who received ≥1 dose of radium dichloride-223 at four academic and one community urology-specific cancer centers from May 2013 to June 2014 were retrospectively identified. Association of baseline and on-therapy clinical variables with number of radium doses received and clinical outcomes including overall survival were analyzed using chi-square statistics, cox proportional hazards, and Kaplan-Meier methods...
December 19, 2016: Prostate
https://www.readbyqxmd.com/read/27981431/adjusting-overall-survival-estimates-after-treatment-switching-a-case-study-in-metastatic-castration-resistant-prostate-cancer
#15
Konstantina Skaltsa, Cristina Ivanescu, Shevani Naidoo, De Phung, Stefan Holmstrom, Nicholas R Latimer
BACKGROUND: If patients in oncology trials receive subsequent therapy, standard intention-to-treat (ITT) analyses may inaccurately estimate the overall survival (OS) effect of the investigational product. In this context, a post-hoc analysis of the phase 3 PREVAIL study was performed with the aim to compare enzalutamide with placebo in terms of OS, adjusting for potential confounding from switching to antineoplastic therapies that are not part of standard metastatic castration-resistant prostate cancer (mCRPC) treatment pathways in some jurisdictions...
December 15, 2016: Targeted Oncology
https://www.readbyqxmd.com/read/27979508/re-efficacy-and-safety-of-enzalutamide-versus-bicalutamide-for-patients-with-metastatic-prostate-cancer-terrain-a-randomised-double-blind-phase-2-study
#16
https://www.readbyqxmd.com/read/27979426/nuclear-specific-ar-v7-protein-localization-is-necessary-to-guide-treatment-selection-in-metastatic-castration-resistant-prostate-cancer
#17
Howard I Scher, Ryon P Graf, Nicole A Schreiber, Brigit McLaughlin, David Lu, Jessica Louw, Daniel C Danila, Lyndsey Dugan, Ann Johnson, Glenn Heller, Martin Fleisher, Ryan Dittamore
BACKGROUND: Circulating tumor cells (CTCs) expressing AR-V7 protein localized to the nucleus (nuclear-specific) identify metastatic castration-resistant prostate cancer (mCRPC) patients with improved overall survival (OS) on taxane therapy relative to the androgen receptor signaling inhibitors (ARSi) abiraterone acetate, enzalutamide, and apalutamide. OBJECTIVE: To evaluate if expanding the positivity criteria to include both nuclear and cytoplasmic AR-V7 localization ("nuclear-agnostic") identifies more patients who would benefit from a taxane over an ARSi...
December 12, 2016: European Urology
https://www.readbyqxmd.com/read/27972629/analysis-of-pharmacy-claims-for-high-cost-oncology-products-abiraterone-and-enzalutamide-usage-in-mcrpc-in-ireland
#18
S Spillane, L M McCullagh, M Barry, C Usher
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/27972459/number-needed-to-treat-and-cost-per-clinically-meaningful-outcome-of-enzalutamide-and-abiraterone-acetate-for-the-treatment-of-metastatic-castration-resistant-prostate-cancer-that-failed-androgen-deprivation-therapy-in-brazil
#19
A P Sasse, G Lopes, V Teich, A P Fay, M Abadi, N M Schultz, S Stefani
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/27942507/impact-of-enzalutamide-on-patient-related-outcomes-in-metastatic-castration-resistant-prostate-cancer-current-perspectives
#20
REVIEW
Jia Luo, Julie N Graff
Prostate cancer claims the lives of more than 25,000 men in the United States yearly, most from metastatic disease. In the past decade, several new medications have been approved for the treatment of metastatic prostate cancer including the antiandrogen enzalutamide. In addition, there has been mounting interest in evaluating health-related quality of life (QoL) in patients with cancer including new more detailed recommendations released by the Prostate Cancer Working Group 3 on how to evaluate patient-related outcomes in clinical trials...
2016: Research and Reports in Urology
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