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Metastatic castrate resistant prostate cancer

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https://www.readbyqxmd.com/read/29222530/seizure-rates-in-enzalutamide-treated-men-with-metastatic-castration-resistant-prostate-cancer-and-risk-of-seizure-the-upward-study
#1
Susan Slovin, William Clark, Joan Carles, Andrew Krivoshik, Jung Wook Park, Fong Wang, Daniel George
Importance: The androgen receptor inhibitor enzalutamide prolongs survival in men with metastatic castration-resistant prostate cancer (mCRPC). In controlled clinical studies, 0.5% (10 of 2051) of patients experienced seizure, but patients with a history of or risk factors for seizure were excluded. Men with mCRPC and seizure risk factors have an estimated seizure rate of 2.8 per 100 patient-years without enzalutamide exposure. Objective: To assess seizure incidence in patients with seizure risk factors who were receiving enzalutamide for mCRPC...
December 7, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/29213237/effectiveness-of-deferred-combined-androgen-blockade-therapy-predicts-efficacy-in-abiraterone-acetate-treated-metastatic-castration-resistant-prostate-cancer-patients-after-docetaxel
#2
Jian-Ri Li, Kun-Yuan Chiu, Shian-Shiang Wang, Cheng-Kuang Yang, Chuan-Shu Chen, Hao-Chung Ho, Chi-Feng Hung, Chen-Li Cheng, Chi-Rei Yang, Cheng-Che Chen, Shu-Chi Wang, Chia-Yen Lin, Chao-Hsiang Chang, Chiann-Yi Hsu, Yen-Chuan Ou
Introduction: Conventional anti-androgen regimens were widely used as an initiation or combined androgen blockade (CAB) therapy in advanced prostate cancer patients. Currently, new androgen pathway inhibitors such as abiraterone acetate (AA) and enzalutamide had been proven effective in metastatic castration resistant prostate cancer. In this study, we attempt to analyze the role of conventional anti-androgen drugs as deferred CAB therapy in castration-resistant prostate cancer patients. Materials and Methods: From 2012 to 2017, 48 metastatic castration-resistant prostate cancer (CRPC) patients who received sequential treatments with primary androgen blockade, oral anti-androgen regimens, and docetaxel followed by AA treatment were included...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29212226/transcribed-ultraconserved-region-uc-63-promotes-resistance-to-docetaxel-through-regulation-of-androgen-receptor-signaling-in-prostate-cancer
#3
Yohei Sekino, Naoya Sakamoto, Keisuke Goto, Ririno Honma, Yoshinori Shigematsu, Kazuhiro Sentani, Naohide Oue, Jun Teishima, Akio Matsubara, Wataru Yasui
Docetaxel is the standard chemotherapy for metastatic castration-resistant prostate cancer (CRPC). However, nearly all patients ultimately become refractory due to the development of docetaxel resistance. The transcribed ultraconserved regions (T-UCRs) are a novel class of non-coding RNAs that are absolutely conserved across species and are involved in carcinogenesis including prostate cancer (PC). In this study, we investigated the transcriptional levels of 26 representative T-UCRs and determined the regions that were differentially expressed in PC...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29207190/anticancer-potential-of-novel-curcumin-analogs-towards-castrate-resistant-prostate-cancer
#4
Shuli Chen, Mhairi Nimick, Andrew G Cridge, Bill C Hawkins, Rhonda J Rosengren
Prostate cancer is initially sensitive to hormone therapy; however, over time the majority of patients progress to a hormone-insensitive form classified as castration-resistant prostate cancer (CRPC). CRPC is highly metastatic and patients have a poor prognosis. Thus, new drugs for the treatment of this disease are required. In this study, we therefore examined the cytotoxic effects and anticancer mechanism(s) of action of second generation curcumin analogs towards CRPC cells. For this purpose, PC3 and DU145 cells were treated with a series of curcumin analogs at 0-10 µM for 72 h and cytotoxicity was determined by the sulforhodamine B (SRB) assay...
November 20, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29206995/concordance-of-circulating-tumor-dna-and-matched-metastatic-tissue-biopsy-in-prostate-cancer
#5
Alexander W Wyatt, Matti Annala, Rahul Aggarwal, Kevin Beja, Felix Feng, Jack Youngren, Adam Foye, Paul Lloyd, Matti Nykter, Tomasz M Beer, Joshi J Alumkal, George V Thomas, Robert E Reiter, Matthew B Rettig, Christopher P Evans, Allen C Gao, Kim N Chi, Eric J Small, Martin E Gleave
Background: Real-time knowledge of the somatic genome can influence management of patients with metastatic castration-resistant prostate cancer (mCRPC). While routine metastatic tissue biopsy is challenging in mCRPC, plasma circulating tumor DNA (ctDNA) has emerged as a minimally invasive tool to sample the tumor genome. However, no systematic comparisons of matched "liquid" and "solid" biopsies have been performed that would enable ctDNA profiling to replace the need for direct tissue sampling...
December 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29198331/biomarkers-in-prostate-cancer-current-clinical-utility-and-future-perspectives
#6
REVIEW
Alexander Kretschmer, Derya Tilki
Current tendencies in the treatment course of prostate cancer patients increase the need for reliable biomarkers that help in decision-making in a challenging clinical setting. Within the last decade, several novel biomarkers have been introduced. In the following comprehensive review article, we focus on diagnostic (PHI®, 4K score, SelectMDx®, ConfirmMDx®, PCA3, MiPS, ExoDX®, mpMRI) and prognostic (OncotypeDX GPS®, Prolaris®, ProMark®, DNA-ploidy, Decipher®) biomarkers that are in widespread clinical use and are supported by evidence...
December 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29196208/eradicate-a-prospective-evaluation-combining-radium-223-dichloride-and-abiraterone-acetate-plus-prednisone-in-patients-with-castration-resistant-prostate-cancer
#7
Neal D Shore, Ronald F Tutrone, Neil F Mariados, Luke T Nordquist, Bryan A Mehlhaff, Karyn J Steere, Stacey S Harrelson
BACKGROUND: Multiple castration-resistant prostate cancer (CRPC) therapies are approved by the United States Food and Drug Administration. Radium-223 dichloride (Ra-223) with abiraterone acetate plus prednisone have different mechanisms of action and distinct off-target side-effect profiles. We prospectively investigated their combined safety, tolerability, and patient-reported outcome measures. PATIENTS AND METHODS: eRADicAte, an investigator-initiated, phase II trial, studied 31 patients with metastatic CRPC, from 5 United States uro-oncology research sites...
November 7, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29191973/blocking-the-feedback-loop-between-neuroendocrine-differentiation-and-macrophages-improves-the-therapeutic-effects-of-enzalutamide-mdv3100-on-prostate-cancer
#8
Chao Wang, Guang Peng, Hai Huang, Fei Liu, De-Pei Kong, Ke-Qin Dong, Li-He Dai, Zhe Zhou, Kai-Jian Wang, Jun Yang, Yan-Qiong Cheng, Xu Gao, Min Qu, Hongru Wang, Feng Zhu, Qin-Qin Tian, Dan Liu, Li Cao, Xingang Cui, Chuanliang Xu, Dan-Feng Xu, Yinghao Sun
PURPOSE: Androgen-deprivation therapy (ADT), including enzalutamide, induces resistance in prostate cancer (PCa); ADT resistance is associated with neuroendocrine differentiation (NED) and tumor-associated macrophages (TAMs). This study aimed to investigate the association between enzalutamide-induced NED and TAMs and its mechanism. EXPERIMENTAL DESIGN: The association between enzalutamide-induced NED and TAMs was investigated by immunohistochemistry using PCa tissues, enzalutamide-resistant mouse xenografts and a co-culture system...
November 30, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29191639/population-based-analysis-of-treatment-toxicity-among-men-with-castration-resistant-prostate-cancer-a-phase-iv-study
#9
Christopher J D Wallis, Raj Satkunasivam, Refik Saskin, Symron Bansal, Girish S Kulkarni, Urban Emmenegger, Robert K Nam
OBJECTIVE: To assess the toxicity and effectiveness of contemporary metastatic castrate-resistant prostate cancer (mCRPC) treatments at a population-level, among all patients in Ontario particularly treated with newer agents including abiraterone, enzalutamide, docetaxel and cabazitaxel. METHODS: We performed a population-based, retrospective cohort study of 2439 men aged ≥65 years treated for mCRPC with abiraterone, enzalutamide, docetaxel, or cabazitaxel from 2003-2015 in Ontario, Canada...
November 27, 2017: Urology
https://www.readbyqxmd.com/read/29187435/evaluating-metformin-as-a-potential-chemosensitizing-agent-when-combined-with-docetaxel-chemotherapy-in-castration-resistant-prostate-cancer-cells
#10
Michelle J Mayer, Laurence H Klotz, Vasundara Venkateswaran
BACKGROUND/AIM: Docetaxel, the first-line chemotherapy for metastatic castration-resistant prostate cancer (mCRPC), provides certain survival benefits, but is associated with significant toxicity. A novel therapeutic approach for mCRPC is combining docetaxel with a chemosensitizing agent. We hypothesized that metformin, a potential chemosensitizer, would improve docetaxel efficacy in CRPC cells. MATERIALS AND METHODS: MTS assays were used to determine the effect of metformin-docetaxel treatment on PC3 and DU145 cell viability...
December 2017: Anticancer Research
https://www.readbyqxmd.com/read/29185010/preliminary-results-on-response-assessment-using-68ga-hbed-cc-psma-pet-ct-in-patients-with-metastatic-prostate-cancer-undergoing-docetaxel-chemotherapy
#11
Anna Katharina Seitz, Isabel Rauscher, Bernhard Haller, Markus Krönke, Sophia Luther, Matthias M Heck, Thomas Horn, Jürgen E Gschwend, Markus Schwaiger, Matthias Eiber, Tobias Maurer
PURPOSE: To investigate the value of 68Ga-HBED-CC PSMA (68Ga-PSMA) PET/CT for response assessment in metastatic castration-sensitive and castration-resistant prostate cancer (mCSPC and mCRPC) during docetaxel chemotherapy. METHODS: 68Ga-PSMA PET/CT was performed in seven mCSPC patients before and after six cycles of upfront docetaxel chemotherapy and in 16 mCRPC patients before and after three cycles of palliative docetaxel chemotherapy. Radiographic treatment response was evaluated separately on the 68Ga-PSMA PET and CT datasets...
November 28, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29183960/radium-223-safety-efficacy-and-concurrent-use-with-abiraterone-or-enzalutamide-first-u-s-experience-from-an-expanded-access-program
#12
Oliver Sartor, Nicholas J Vogelzang, Christopher Sweeney, Daniel C Fernandez, Fabio Almeida, Andrei Iagaru, Alan Brown, Matthew R Smith, Manish Agrawal, Adam P Dicker, Jorge A Garcia, Jose Lutzky, Yu-Ning Wong, Oana Petrenciuc, Jeremy Gratt, Neal D Shore, Michael J Morris
BACKGROUND: In the phase III ALSYMPCA trial, metastatic castration-resistant prostate cancer (mCRPC) patients had few prior life-prolonging therapies. Following ALSYMPCA, which demonstrated radium-223 survival benefit, and before radium-223 U.S. commercial availability, an expanded access program (EAP) providing early-access radium-223 allowed life-prolonging therapies in current use. SUBJECTS, MATERIALS, AND METHODS: This phase II, open-label, single-arm, multicenter U...
November 28, 2017: Oncologist
https://www.readbyqxmd.com/read/29180633/integrating-evolutionary-dynamics-into-treatment-of-metastatic-castrate-resistant-prostate-cancer
#13
Jingsong Zhang, Jessica J Cunningham, Joel S Brown, Robert A Gatenby
Abiraterone treats metastatic castrate-resistant prostate cancer by inhibiting CYP17A, an enzyme for testosterone auto-production. With standard dosing, evolution of resistance with treatment failure (radiographic progression) occurs at a median of ~16.5 months. We hypothesize time to progression (TTP) could be increased by integrating evolutionary dynamics into therapy. We developed an evolutionary game theory model using Lotka-Volterra equations with three competing cancer "species": androgen dependent, androgen producing, and androgen independent...
November 28, 2017: Nature Communications
https://www.readbyqxmd.com/read/29174502/lymph-node-response-in-a-patient-with-metastatic-castration-resistant-prostate-cancer-treated-with-radium-223
#14
Darren M C Poon, Kenneth C W Wong
No abstract text is available yet for this article.
November 7, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29173976/phase-2-study-of-weekly-paclitaxel-plus-estramustine-in-metastatic-hormone-refractory-prostate-carcinoma-ecog-acrin-cancer-research-group-e1898-trial
#15
Yu-Ning Wong, Judith Manola, Gary R Hudes, Bruce J Roth, Judd W Moul, Andrea M Barsevick, Richard M Scher, Michael J Volk, David J Vaughn, Stephen D Williams, Michael J Fisch, David Cella, Michael A Carducci, George Wilding
INTRODUCTION: This multicenter phase 2 study assessed the combination of estramustine and weekly paclitaxel with metastatic castration-resistant prostate cancer (CRPC). PATIENTS AND METHODS: We enrolled 77 patients who had received no prior chemotherapy for CRPC between 1998 and 2000; a total of 74 subjects were eligible for the study. Each 8-week cycle included paclitaxel 90 mg/m2 provided intravenously weekly for 6 weeks, followed by 2 weeks off therapy and oral estramustine 280 mg twice daily for 3 days beginning 24 hours before the first dose of paclitaxel...
October 16, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29170762/clinical-utility-of-clia-grade-ar-v7-testing-in-patients-with-metastatic-castration-resistant-prostate-cancer
#16
Mark C Markowski, John L Silberstein, James R Eshleman, Mario A Eisenberger, Jun Luo, Emmanuel S Antonarakis
Purpose: A splice variant of the androgen receptor, AR-V7, confers resistance to AR-targeted therapies (ATTs) but not taxane chemotherapies in patients with metastatic castration-resistant prostate cancer. Since August 2015, a clinical-grade assay to detect AR-V7 messenger RNA expression in circulating tumors cells (CTCs) has been available to providers through a Clinical Laboratory Improvement Amendments-certified laboratory at Johns Hopkins University. Methods: We contacted ordering providers of the first 150 consecutive tests by using a questionnaire-based survey to determine how the results of AR-V7 testing were used to influence clinical practice...
2017: JCO Precision Oncology
https://www.readbyqxmd.com/read/29166333/high-energy-collimator-is-preferable-to-medium-energy-collimator-for-evaluating-223ra-uptake-in-bone-metastasis-at-2-weeks-postinjection
#17
Akira Ichimura, Tadaki Nakahara, Yoshiki Owaki, Kiyotaka Nakajima, Masahiro Jinzaki
An 80-year-old man with castration-resistant prostate cancer received Ra injection to treat bone metastases. Two weeks after the injection, the patient underwent static Ra scan of the chest with medium-energy and high-energy collimators for 30 minutes each. Images obtained with the 2 collimators showed that uptake in metastatic lesions was visually clearer and semiquantitatively higher with the high-energy collimator. The use of HE collimator for Ra imaging in the early phase has been reported, and the present case suggests that in the late phase HE collimator would also be preferable to medium-energy collimator in terms of lesion-based evaluation...
November 22, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/29166331/223ra-therapy-in-patients-with-advanced-castration-resistant-prostate-cancer-with-bone-metastases-lessons-from-daily-practice
#18
Maarten J van der Doelen, Malou C P Kuppen, Marianne A Jonker, Niven Mehra, Marcel J R Janssen, Inge M van Oort, Winald R Gerritsen
PURPOSE: To identify pre-therapeutic variables associated with overall survival (OS) in patients treated with Ra. METHODS: Data from 45 CRPC patients treated with Ra were retrospectively analyzed. All patients who received at least one Ra injection were included in the study. Cox proportional hazard regression models were used to estimate hazard ratio's (HR) and to test for association. RESULTS: Twenty-one patients (47%) received six Ra injections and 24 patients (53%) received one to five Ra injections...
November 22, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/29164346/impact-of-prior-androgen-receptor-axis-targeted-agents-on-the-clinical-activity-of-subsequent-docetaxel-in-patients-with-metastatic-castration-resistant-prostate-cancer-comparative-assessment-between-abiraterone-acetate-and-enzalutamide
#19
Hideaki Miyake, Yuto Matsushita, Keita Tamura, Daisuke Motoyama, Toshiki Ito, Takayuki Sugiyama, Atsushi Otsuka
The objective of this study was to investigate the impact of prior treatment with androgen receptor-axis-targeted (ARAT) agents, abiraterone acetate (AA) and enzalutamide (Enz), on the activity of subsequently introduced docetaxel in patients with metastatic castration-resistant prostate cancer (mCRPC). This study included a total of 114 mCRPC patients consisting of 54 and 60 who progressed following treatment with AA and Enz, respectively, prior to the introduction of docetaxel, and compared oncological outcomes with docetaxel between these two groups...
November 21, 2017: Medical Oncology
https://www.readbyqxmd.com/read/29163793/rapid-ultra-low-coverage-copy-number-profiling-of-cell-free-dna-as-a-precision-oncology-screening-strategy
#20
Daniel H Hovelson, Chia-Jen Liu, Yugang Wang, Qing Kang, James Henderson, Amy Gursky, Scott Brockman, Nithya Ramnath, John C Krauss, Moshe Talpaz, Malathi Kandarpa, Rashmi Chugh, Missy Tuck, Kirk Herman, Catherine S Grasso, Michael J Quist, Felix Y Feng, Christine Haakenson, John Langmore, Emmanuel Kamberov, Tim Tesmer, Hatim Husain, Robert J Lonigro, Dan Robinson, David C Smith, Ajjai S Alva, Maha H Hussain, Arul M Chinnaiyan, Muneesh Tewari, Ryan E Mills, Todd M Morgan, Scott A Tomlins
Current cell-free DNA (cfDNA) next generation sequencing (NGS) precision oncology workflows are typically limited to targeted and/or disease-specific applications. In advanced cancer, disease burden and cfDNA tumor content are often elevated, yielding unique precision oncology opportunities. We sought to demonstrate the utility of a pan-cancer, rapid, inexpensive, whole genome NGS of cfDNA approach (PRINCe) as a precision oncology screening strategy via ultra-low coverage (~0.01x) tumor content determination through genome-wide copy number alteration (CNA) profiling...
October 27, 2017: Oncotarget
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