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Treatment resistant mCRPC

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https://www.readbyqxmd.com/read/28938672/comparing-the-clinical-efficacy-of-abiraterone-acetate-enzalutamide-and-orteronel-in-patients-with-metastatic-castration-resistant-prostate-cancer-by-performing-a-network-meta-analysis-of-eight-randomized-controlled-trials
#1
Minyong Kang, Chang Wook Jeong, Cheol Kwak, Ja Hyeon Ku, Hyeon Hoe Kim
Various novel androgen receptor (AR) targeting drugs have been developed recently and have shown beneficial effects on survival in patients with metastatic castration-resistant prostate cancer (mCRPC). However, no consensus has been reached regarding which of these agents provides the most favorable oncological outcomes. Here, we aimed to compare the efficacy of novel AR-targeted agents by performing a network meta-analysis of randomized controlled trials (RCTs). We included eight RCTs for men with mCRPC treated with one of the AR targeting agents: abiraterone acetate, enzalutamide, or orteronel...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915573/lipid-catabolism-inhibition-sensitizes-prostate-cancer-cells-to-antiandrogen-blockade
#2
Thomas W Flaig, Maren Salzmann-Sullivan, Lih-Jen Su, Zhiyong Zhang, Molishree Joshi, Miguel A Gijón, Jihye Kim, John J Arcaroli, Adrie Van Bokhoven, M Scott Lucia, Francisco G La Rosa, Isabel R Schlaepfer
Prostate cancer (PCa) is the most common malignancy among Western men and the second leading-cause of cancer related deaths. For men who develop metastatic castration resistant PCa (mCRPC), survival is limited, making the identification of novel therapies for mCRPC critical. We have found that deficient lipid oxidation via carnitine palmitoyltransferase (CPT1) results in decreased growth and invasion, underscoring the role of lipid oxidation to fuel PCa growth. Using immunohistochemistry we have found that the CPT1A isoform is abundant in PCa compared to benign tissue (n=39, p<0...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28906339/multiparametric-magnetic-resonance-imaging-of-prostate-cancer-bone-disease-correlation-with-bone-biopsy-histological-and-molecular-features
#3
Raquel Perez-Lopez, Daniel Nava Rodrigues, Ines Figueiredo, Joaquin Mateo, David J Collins, Dow-Mu Koh, Johann S de Bono, Nina Tunariu
OBJECTIVES: The aim of this study was to correlate magnetic resonance imaging (MRI) of castration-resistant prostate cancer (CRPC) bone metastases with histological and molecular features of bone metastases. MATERIALS AND METHODS: Forty-three bone marrow biopsies from 33 metastatic CRPC (mCRPC) patients with multiparametric MRI and documented bone metastases were evaluated. A second cohort included 10 CRPC patients with no bone metastases. Associations of apparent diffusion coefficient (ADC), normalized b900 diffusion-weighted imaging (nDWI) signal, and signal-weighted fat fraction (swFF) with bone marrow biopsy histological parameters were evaluated using Mann-Whitney U test and Spearman correlations...
September 12, 2017: Investigative Radiology
https://www.readbyqxmd.com/read/28905815/psa-time-to-nadir-as-a-prognostic-factor-of-first-line-docetaxel-treatment-in-castration-resistant-prostate-cancer-evidence-from-patients-in-northwestern-china
#4
Kai-Jie Wu, Xin-Qi Pei, Ge Tian, Da-Peng Wu, Jin-Hai Fan, Yu-Mei Jiang, Da-Lin He
Docetaxel-based chemotherapy remains the first-line treatment for patients with metastatic castration-resistant prostate cancer (mCRPC) in China; however, the prognostic factors associated with effects in these patients are still controversial. In this study, we retrospectively reviewed the data from 71 eligible Chinese patients who received docetaxel chemotherapy from 2009 to 2016 in our hospital and experienced a reduction of prostate-specific antigen (PSA) level ≥50% during the treatment and investigated the potential role of time to nadir (TTN) of PSA...
September 12, 2017: Asian Journal of Andrology
https://www.readbyqxmd.com/read/28903426/the-prognostic-implication-of-intraductal-carcinoma-of-the-prostate-in-metastatic-castration-resistant-prostate-cancer-and-its-potential-predictive-value-in-those-treated-with-docetaxel-or-abiraterone-as-first-line-therapy
#5
Jinge Zhao, Pengfei Shen, Guangxi Sun, Ni Chen, Jiandong Liu, Xin Tang, Rui Huang, Diming Cai, Jing Gong, Xingming Zhang, Zhibin Chen, Xiang Li, Qiang Wei, Peng Zhang, Zhenhua Liu, Jiyan Liu, Hao Zeng
Intraductal carcinoma of the prostate (IDC-P) is recognized as a newly pathological entity in 2016 WHO classification. It's role in metastatic castration-resistant prostate cancer (CRPC) remains obscure. We aimed to explore the association of IDC-P with clinical outcome and to further identify its potential predictive role in making first-line treatment decisions for mCRPC. We retrospectively analyzed data of 131 mCRPC patients. IDC-P was diagnosed by re-biopsy at the time of mCRPC. Among total patients, 45 and 41 received abiraterone or docetaxel as first-line therapies, respectively...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903376/improving-circulating-tumor-cells-enumeration-and-characterization-to-predict-outcome-in-first-line-chemotherapy-mcrpc-patients
#6
Luis León-Mateos, Helena Casas, Alicia Abalo, María Vieito, Manuel Abreu, Urbano Anido, Antonio Gómez-Tato, Rafael López, Miguel Abal, Laura Muinelo-Romay
INTRODUCTION: There is a critical need of new surrogate markers for improving the therapeutic selection and monitoring of metastatic prostate cancer patients. Nowadays clinical management of these patients is been driven by biochemical and clinical parameters without enough accuracy to allow a real personalized medicine. The present study was conducted to go insight the molecular profile of circulating tumor cells (CTCs) isolated from advanced metastatic castration-resistant prostate cancer (mCRPC) with the aim of identifying prognostic marker with potential utility for therapy selection and monitoring...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28895177/a-novel-use-for-olaparib-for-treatment-of-metastatic-castration-recurrent-prostate-cancer
#7
Grace A Martin, Adrienne H Chen, Kinjal Parikh
Although mortality from prostate cancer has declined over the past 20 years as a result of early detection and treatment, the 5-year survival rate for men with prostate cancer who develop metastatic disease is only 29%. Current treatment options for metastatic castration-recurrent prostate cancer (mCRPC) are associated with toxicity and a limited durable response; therefore, additional lines of efficacious and minimally toxic therapy are needed. Olaparib, a poly(adenosine 5'-diphosphate) ribose polymerase (PARP) inhibitor, received United States Food and Drug Administration breakthrough therapy designation in January 2016 for the treatment of patients with BRCA1/2 or ATM gene-mutated mCRPC based on results of a compelling phase II trial of olaparib in patients with advanced castration resistant prostate cancer (TOPARP-A)...
September 12, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28881501/drug-drug-interaction-potential-in-men-treated-with-enzalutamide-mind-the-gap
#8
G E Benoist, I M van Oort, S Smeenk, A Javad, D M Somford, D M Burger, N Mehra, N P van Erp
AIM: Metastatic castration resistant prostate cancer (mCRPC) patients are generally older patients with several co-morbidities and are therefore more at risk for complications due to drug-drug interactions(DDIs). We assessed the prevalence of potential DDIs in a cohort of mCRPC patients treated with enzalutamide. METHODS: We conducted a retrospective review of pharmacy records to retrieve individual drug histories of mCRPC patients who started enzalutamide therapy in a tertiary care setting...
September 7, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28874892/treatment-patterns-and-trends-in-patients-dying-of-prostate-cancer-in-quebec-a-population-based-study
#9
A Dragomir, J Rocha, M Vanhuyse, F L Cury, W Kassouf, J Hu, A G Aprikian
INTRODUCTION: Since just after the year 2000 in Quebec, the management of metastatic castration-resistant prostate cancer (mcrpc) has evolved considerably, with the inclusion of docetaxel-based chemotherapy, bone-targeted therapies (zoledronic acid and denosumab), and more recently, abiraterone, enzalutamide, and cabazitaxel for docetaxel-refractory patients. In the present study, we aimed to analyze contemporary mcrpc management patterns and therapy utilization trends in Quebec. METHODS: The study cohort consisted of patients dying of prostate cancer (pca) between January 2001 and December 2013, selected from Quebec public health care insurance databases...
August 2017: Current Oncology
https://www.readbyqxmd.com/read/28873372/efficacy-and-safety-of-the-oral-multikinase-regorafenib-in-metastatic-colorectal-cancer
#10
Giuseppe Cicero, Rossella De Luca, Francesco Dieli
BACKGROUND/AIM: A clinical trial demonstrated that treatment with oral multikinase regorafenib improved overall survival (OS), progression-free survival (PFS), and disease control [García-Alfonso et al.: J Clin Transl Oncol 2016;18:1072-1081; Bertocchi et al.: J Chemother 2017;29:102-105]. In this study, we aimed to evaluate its effectiveness in Italian patients with hormone-refractory metastatic castration-resistant prostate cancer (mCRPC) progressing after chemotherapy with docetaxel plus prednisone...
September 6, 2017: Oncology
https://www.readbyqxmd.com/read/28870943/prospective-evaluation-of-neuromediator-dynamics-in-castration-resistant-prostate-cancer-patients-during-docetaxel
#11
MULTICENTER STUDY
Jost VON Hardenberg, Maike Schwartz, Thorsten Werner, Stefan Fuxius, Markus Müller, Thomas Frangenheim, Christian Bolenz, Christel Weiss, Elmar Heinrich
AIM: Aim of the study was to detect small cell/neuroendocrine (SCNC) transformation in metastatic castration-resistant prostate cancer (mCRPC) that is a challenging procedure. We investigated the role of neuromediator dynamics as potential evidence of SCNC in patients undergoing docetaxel therapy. PATIENTS AND METHODS: A multi-institutional, prospective observational study was conducted. Patients undergoing docetaxel treatment were included. Chromogranin A (CGA), neuron-specific enolase (NSE), and pro-gastrin releasing peptide (Pro-GRP) were sequentially evaluated at predefined time points...
September 2017: Anticancer Research
https://www.readbyqxmd.com/read/28866255/novel-junction-specific-and-quantifiable-in-situ-detection-of-ar-v7-and-its-clinical-correlates-in-metastatic-castration-resistant-prostate-cancer
#12
Yezi Zhu, Adam Sharp, Courtney M Anderson, John L Silberstein, Maritza Taylor, Changxue Lu, Pei Zhao, Angelo M De Marzo, Emmanuel S Antonarakis, Mindy Wang, Xingyong Wu, Yuling Luo, Nan Su, Daniel Nava Rodrigues, Ines Figueiredo, Jonathan Welti, Emily Park, Xiao-Jun Ma, Ilsa Coleman, Colm Morrissey, Stephen R Plymate, Peter S Nelson, Johann S de Bono, Jun Luo
BACKGROUND: Androgen receptor splice variant 7 (AR-V7) has been implicated in resistance to abiraterone and enzalutamide treatment in men with metastatic castration-resistant prostate cancer (mCRPC). Tissue- or cell-based in situ detection of AR-V7, however, has been limited by lack of specificity. OBJECTIVE: To address current limitations in precision measurement of AR-V7 by developing a novel junction-specific AR-V7 RNA in situ hybridization (RISH) assay compatible with automated quantification...
August 30, 2017: European Urology
https://www.readbyqxmd.com/read/28860817/cabazitaxel-in-the-treatment-of-metastatic-castration-resistant-prostate-cancer-patient-selection-and-special-considerations
#13
REVIEW
Sheel A Patel, Jean Hoffman-Censits
Cabazitaxel is an effective chemotherapeutic agent used in the treatment of metastatic castration-resistant prostate cancer (mCRPC) refractory to docetaxel. With the advent of new antiandrogen therapies, immune-based treatments, and radioactive-targeted therapy, there are now multiple effective and approved agents for this disease state. The optimal sequencing of these agents is unclear as there are no large-scale head-to-head comparisons. Clinicians must familiarize themselves with the most recent studies as well as drug toxicities to determine the best treatment option for their patients...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28844372/antitumour-activity-and-safety-of-enzalutamide-in-patients-with-metastatic-castration-resistant-prostate-cancer-previously-treated-with-abiraterone-acetate-plus-prednisone-for-%C3%A2-24-weeks-in-europe
#14
Johann S de Bono, Simon Chowdhury, Susan Feyerabend, Tony Elliott, Enrique Grande, Amal Melhem-Bertrandt, Benoit Baron, Mohammad Hirmand, Patrick Werbrouck, Karim Fizazi
BACKGROUND: Enzalutamide and abiraterone acetate plus prednisone, which target the androgen receptor axis, have expanded the treatment of advanced prostate cancer. Retrospective analyses suggest some cross-resistance between these two drugs when used sequentially, but robust, prospective studies have not yet been reported. OBJECTIVE: To fulfil a regulatory postregistration commitment by evaluating the efficacy and safety of enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) who progressed following abiraterone acetate plus prednisone treatment...
August 22, 2017: European Urology
https://www.readbyqxmd.com/read/28836852/do-the-expressions-of-epithelial-mesenchymal-transition-proteins-periostin-integrin-%C3%AE-4-and-fibronectin-correlate-with-clinico-pathological-features-and-prognosis-of-metastatic-castration-resistant-prostate-cancer
#15
Ece Konac, Ilker Kiliccioglu, Emrullah Sogutdelen, Asiye U Dikmen, Gulsah Albayrak, Cenk Y Bilen
Development of metastatic castration-resistant prostate cancer is a result of the lack of an apoptotic response by the tumor cells and loss of the ability to stick to adjacent cells through epithelial-mesenchymal transition. Although there are several strongly recommended biomarkers for determining prognosis of metastatic castration-resistant prostate cancer, only few of them may help decide the selection of the optimal treatment option. The mode of treatment sequencing in metastatic castration-resistant prostate cancer will be based on the individual characteristics of the patient...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28836508/circulating-tumor-cells-and-their-role-in-prostate-cancer
#16
REVIEW
Moritz Maas, Miriam Hegemann, Steffen Rausch, Jens Bedke, Arnulf Stenzl, Tilman Todenhöfer
Circulating tumor cells (CTC) have become an important biomarker in patients with advanced prostate cancer. CTC count has been demonstrated to be a prognostic factor for overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC). In localized prostate cancer, a clear correlation between CTC counts and clinicopathological risk parameters and outcome has not been observed. Currently, the focus of research is shifting from CTC enumeration towards molecular characterization of CTC leading to the discovery of markers predicting treatment response...
August 22, 2017: Asian Journal of Andrology
https://www.readbyqxmd.com/read/28826931/comparison-of-sequential-treatment-with-androgen-receptor-targeted-agent-followed-by%C3%A2-another-androgen-receptor-targeted-agent-versus-androgen-receptor-targeted-agent-followed-by-docetaxel-in-chemotherapy-naive-patients-with-metastatic-castration-resistant
#17
Nobuaki Matsubara, Yoko Yamada, Ken-Ichi Tabata, Takefumi Satoh, Naoto Kamiya, Hiroyoshi Suzuki, Takashi Kawahara, Hiroji Uemura, Akihiro Yano, Satoru Kawakami, Masafumi Otsuka, Satoshi Fukasawa
BACKGROUND: An important clinical question of great interest to clinicians is how to best sequence androgen receptor targeted agents (ARTAs) and chemotherapy for metastatic castration-resistant prostate cancer (mCRPC), but the answer is still unclear. MATERIALS AND METHODS: To evaluate and compare the clinical outcomes of ARTA and docetaxel (DTX) as second-line treatment in the post first-line ARTA, we conducted a retrospective analysis of chemotherapy-naive mCRPC patients who had received sequential treatment with ARTA followed by another ARTA (ARTA-ARTA) or ARTA followed by DTX (ARTA-DTX)...
July 26, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28819727/abiraterone-acetate-a-review-in-metastatic-castration-resistant-prostrate-cancer
#18
Lesley J Scott
Oral abiraterone acetate (Zytiga(®)) is a selective inhibitor of CYP17 and thereby inhibits androgen biosynthesis, with androgen signalling crucial in the progression from primary to metastatic prostate cancer (PC) and subsequently, in the development of metastatic castration-resistant PC (mCRPC). In large phase 3 trials and in the clinical practice setting, oral abiraterone acetate in combination with prednisone was an effective treatment and had an acceptable, manageable tolerability and safety profile in chemotherapy-naive and docetaxel-experienced men with mCRPC...
August 17, 2017: Drugs
https://www.readbyqxmd.com/read/28819719/activity-of-cabazitaxel-in-patients-with-metastatic-castration-resistant-prostate-cancer-after-treatment-with-single-or-dual-regimens-of-novel-androgen-receptor-targeting-agents
#19
Yukari Bando, Nobuyuki Hinata, Tomoaki Terakawa, Junya Furukawa, Ken-Ichi Harada, Yuzo Nakano, Masato Fujisawa
The purpose of this study was to evaluate the efficacy of cabazitaxel for patients with metastatic castration-resistant prostate cancer (mCRPC) after sequential therapy with docetaxel (DTX) and single or dual regimens of novel androgen receptor-axis-targeted (ARAT) agents. We retrospectively reviewed 84 consecutive patients treated with cabazitaxel at Kobe University Hospital and related hospitals from September 2014 to September 2016. The association of each prognostic parameter with progression-free survival (PFS) was evaluated, including the sequence of therapy...
August 17, 2017: Medical Oncology
https://www.readbyqxmd.com/read/28819021/phenotypic-heterogeneity-of-circulating-tumor-cells-informs-clinical-decisions-between-ar-signaling-inhibitors-and-taxanes-in-metastatic-prostate-cancer
#20
Howard I Scher, Ryon P Graf, Nicole Schreiber, Brigit McLaughlin, Adam Jendrisak, Yipeng Wang, Jerry Lee, Stephanie Greene, Rachel Krupa, David Lu, Pascal Bamford, Jessica Louw, Lyndsey Dugan, Hebert Alberto Vargas, Martin Fleisher, Mark Landers, Glenn Heller, Ryan V Dittamore
The heterogeneity of an individual patient's tumor has been linked to treatment resistance, but quantitative biomarkers to rapidly and reproducibly evaluate heterogeneity in a clinical setting are currently lacking. Using established tools available in a CAP-accredited and CLIA-certified clinical laboratory, we quantified digital pathology features on 9,225 individual circulating tumor cells (CTCs) from 179 unique metastatic castration-resistant prostate cancer (mCRPC) patients to define phenotypically distinct cell types...
August 17, 2017: Cancer Research
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