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https://www.readbyqxmd.com/read/29046247/optimal-usage-of-radium-223-in-metastatic-castration-resistant-prostate-cancer
#1
REVIEW
Tai-Lung Cha, Tony Tong-Lin Wu, Nicholas John Vogelzang, Chao-Yuan Huang, Shu-Pin Huang, Chia-Chi Lin, Yen-Chuan Ou, See-Tong Pang, Daniel Heung-Yuan Shen, Wen-Jeng Wu, Wayne Yen-Hwa Chang
Radium-223 is a first-in-class α-emitting radiopharmaceutical that targets bone metastases associated with metastatic castration-resistant prostate cancer (mCRPC). In the pivotal phase III trial ALSYMPCA, radium-223 significantly increased overall survival (OS), compared with placebo (median 14.9 vs 11.3 months; hazard ratio 0.70; 95% CI 0.58-0.83; p < 0.001), in patients with mCRPC and symptomatic bone metastases-with a comparable safety profile. To optimize treatment outcomes, selection of appropriate patients is important...
October 15, 2017: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/29038335/preclinical-and-coclinical-studies-in-prostate-cancer
#2
Ming Chen, Pier Paolo Pandolfi
Men who develop metastatic castration-resistant prostate cancer (mCRPC) will invariably succumb to their disease. Thus there remains a pressing need for preclinical testing of new drugs and drug combinations for late-stage prostate cancer (PCa). Insights from the mCRPC genomic landscape have revealed that, in addition to sustained androgen receptor (AR) signaling, there are other actionable molecular alterations and distinct molecular subclasses of PCa; however, the rate at which this knowledge translates into patient care via current preclinical testing is painfully slow and inefficient...
October 16, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/29032717/bet-inhibitors-in-metastatic-prostate-cancer-therapeutic-implications-and-rational-drug-combinations
#3
Mark C Markowski, Angelo M De Marzo, Emmanuel S Antonarakis
The bromodomain and extra-terminal (BET) family of proteins are epigenetic readers of acetylated histones regulating a vast network of protein expression across many different cancers. Therapeutic targeting of BET is an attractive area of clinical development for metastatic castration-resistant prostate cancer (mCRPC), particularly due to its putative effect on c-MYC expression and its interaction with the androgen receptor (AR). Areas Covered: We speculate that a combination approach using BET inhibition with other targeted therapies may be required to improve the therapeutic index of BET inhibition in the management of prostate cancer...
October 16, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29027610/risk-factors-for-and-incidence-of-seizures-in-metastatic-castration-resistant-prostate-cancer-a-real-world-retrospective-cohort-study
#4
Charles Dharmani, Machaon Bonafede, Andrew Krivoshik
BACKGROUND AND OBJECTIVE: This real-world study assessed the prevalence, risk factors for, and incidence of seizures in patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: Patients with mCRPC were selected from MarketScan Commercial and Medicare Supplemental Databases between 1 January 2009 and 31 July 2012. Prevalence of seizure risk factors were described separately and in combination with other risk factors. Seizure incidence was calculated overall and for each risk factor group...
October 13, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/29026946/psma-targeted-radioligandtherapy-in-metastatic-castration-resistant-prostate-cancer-after-chemotherapy-abiraterone-and-or-enzalutamide-a-retrospective-analysis-of-overall-survival
#5
K Rahbar, M Boegemann, A Yordanova, M Eveslage, M Schäfers, M Essler, H Ahmadzadehfar
AIM: Our aim was to evaluate overall survival and parameters prognosticating longer survival in a large and homogeneous group of patients treated with (177)Lu-PSMA-617 radioligand therapy with heavily pretreated advanced metastatic castration resistant prostate cancer. METHODS: A total of 104 patients were treated with 351 cycles of (177)Lu-PSMA-617. Prostate specific antigen (PSA) changes after the first cycle of therapy were documented prior to a second cycle...
October 12, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29026202/loss-of-abhd5-promotes-the-aggressiveness-of-prostate-cancer-cells
#6
Guohua Chen, Guoli Zhou, Siddhesh Aras, Zhenhui He, Stephanie Lucas, Izabela Podgorski, Wael Skar, James G Granneman, Jian Wang
The accumulation of neutral lipids in intracellular lipid droplets has been associated with the formation and progression of many cancers, including prostate cancer (PCa). Alpha-beta Hydrolase Domain Containing 5 (ABHD5) is a key regulator of intracellular neutral lipids that has been recently identified as a tumor suppressor in colorectal cancer, yet its potential role in PCa has not been investigated. Through mining publicly accessible PCa gene expression datasets, we found that ABHD5 gene expression is markedly decreased in metastatic castration-resistant PCa (mCRPC) samples...
October 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28986618/-177-lu-psma-therapy-current-evidence-for-use-in-the-treatment-of-patients-with-metastatic-prostate-cancer
#7
REVIEW
M Boegemann, A J Schrader, K Rahbar
BACKGROUND: Despite significant progress in the treatment of metastatic castration-resistant prostate cancer (mCRPC) in recent years (including agents targeting androgen receptor signaling, chemotherapy, and (223)Ra), most of these patients still succumb to prostate cancer. Recently, (177)lutetium prostate-specific membrane antigen radioligand therapy ((177)Lu-PSMA-RLT) has been increasingly used within compassionate use provisions in these patients in Germany and showed promising efficacy...
October 6, 2017: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/28975586/impact-of-treatment-delay-in-radium-223-therapy-of-metastatic-castration-resistant-prostate-cancer-patients
#8
Marie Øbro Fosbøl, Peter Meidahl Petersen, Gedske Daugaard, Søren Holm, Andreas Kjaer, Jann Mortensen
BACKGROUND: Radium-223-dichloride (Ra-223) is an alpha-emitting, bone seeking radionuclide therapy approved for patients with metastatic castration-resistant prostate cancer (mCRPC). In the fall of 2014, a global temporary shortage of Ra-223 occurred for 2 months due to production irregularities. The aim of this study was to assess whether prolonged interval between Ra-223 cycles to non-disease related causes had a negative impact on clinical outcome of therapy. MATERIALS AND METHODS: Retrospective single-center study of mCRPC patients who initiated Ra-223 therapy in the period from March 2014 to February 2015...
October 3, 2017: Annals of Nuclear Medicine
https://www.readbyqxmd.com/read/28965854/cabazitaxel-conjugated-nanoparticles-for-docetaxel-resistant-and-bone-metastatic-prostate-cancer
#9
Bryan Hoang, Mark J Ernsting, Wei-Hsin Sophia Tang, Joseph Bteich, Elijus Undzys, Taira Kiyota, Shyh-Dar Li
Effective treatment of metastatic castration resistant prostate cancer (mCRPC) remains an unmet challenge. Cabazitaxel (CBZ) is approved for mCRPC after docetaxel (DTX) failure, but the improvement in survival is only moderate (∼2 months) and patients suffer from significant side effects. Here, we report the development of a polymer based delivery system for CBZ to improve its safety and efficacy against DTX-resistant mCRPC. CBZ was conjugated to a carboxymethylcellulose-based polymer (Cellax-CBZ), which self-assembled into ∼100 nm particles in saline and exhibited sustained drug release in serum at 10%/day...
September 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28958629/quality-of-life-in-second-line-treatment-of-metastatic-castration-resistant-prostate-cancer-using-cabazitaxel-or-other-therapies-after-previous-docetaxel-chemotherapy-swiss-observational-treatment-registry
#10
Frank Stenner, Sacha I Rothschild, Daniel Betticher, Clemens Caspar, Rudolf Morant, Razvan Popescu, Daniel Rauch, Urs Huber, Reinhard Zenhäusern, Cyrill Rentsch, Richard Cathomas
BACKGROUND: The aim was to evaluate quality of life (QoL), pain, and fatigue in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with different regimens after first-line docetaxel, as well as disease progression. PATIENTS AND METHODS: Patients with mCRPC having received first-line chemotherapy with docetaxel were eligible. Second-line treatment choice was at the discretion of the local investigator. All patients had regular assessments of QoL with the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire, of fatigue with the Brief Fatigue Inventory, and of pain with the McGill Pain Questionnaire-Short Form...
August 24, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28948170/neutrophil-to-lymphocyte-ratio-predicts-prognosis-in-castration-resistant-prostate-cancer-patients-who-received-cabazitaxel-chemotherapy
#11
Koichi Uemura, Takashi Kawahara, Daisuke Yamashita, Ryosuke Jikuya, Koichi Abe, Tomoyuki Tatenuma, Yumiko Yokomizo, Koji Izumi, Jun-Ichi Teranishi, Kazuhide Makiyama, Yasushi Yumura, Takeshi Kishida, Koichi Udagawa, Kazuki Kobayashi, Yasuhide Miyoshi, Masahiro Yao, Hiroji Uemura
INTRODUCTION AND OBJECTIVES: An elevated neutrophil-to-lymphocyte ratio (NLR) has been suggested to be associated with a poor prognosis in several cancers. We evaluated the utility of an elevated NLR as a biomarker to predict the prognosis of metastatic castration-resistant prostate cancer (mCRPC) patients treated with cabazitaxel (CBZ). METHODS: We analyzed 47 patients who received CBZ chemotherapy for mCRPC in our institutions. The NLR was calculated using the neutrophil and lymphocyte counts before CBZ chemotherapy...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28939004/the-phase-3-cou-aa-302-study-of-abiraterone-acetate-plus-prednisone-in-men-with-chemotherapy-na%C3%A3-ve-metastatic-castration-resistant-prostate-cancer-stratified-analysis-based-on-pain-prostate-specific-antigen-and-gleason-score
#12
Kurt Miller, Joan Carles, Jürgen E Gschwend, Hendrik Van Poppel, Joris Diels, Sabine D Brookman-May
BACKGROUND: In the COU-AA-302 study (NCT00887198), abiraterone acetate plus prednisone (AAP) significantly improved outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) versus prednisone alone. Baseline clinical parameters predicting that treatment response could help inform clinical decisions were explored. OBJECTIVE: To identify patients who derive the greatest clinical benefit from AAP treatment. DESIGN, SETTING, AND PARTICIPANTS: A total of 1088 mCRPC patients treated with either AAP or prednisone in the first-line setting in COU-AA-302 were included in this post hoc analysis...
September 20, 2017: European Urology
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
#13
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/28928853/the-influence-of-prednisone-on-the-efficacy-of-cabazitaxel-in-men-with-metastatic-castration-resistant-prostate-cancer
#14
Carlo Buonerba, Guru Sonpavde, Francesca Vitrone, Davide Bosso, Livio Puglia, Michela Izzo, Simona Iaccarino, Luca Scafuri, Margherita Muratore, Francesca Foschini, Brigitta Mucci, Vincenzo Tortora, Martina Pagliuca, Dario Ribera, Vittorio Riccio, Rocco Morra, Mirta Mosca, Nicola Cesarano, Ileana Di Costanzo, Sabino De Placido, Giuseppe Di Lorenzo
Background: Cabazitaxel is a second-generation taxane that is approved for use with concomitant low dose daily prednisone in metastatic castration resistant prostate cancer (mCRPC) after docetaxel failure. Since the role of daily corticosteroids in improving cabazitaxel efficacy or ameliorating its safety profile has not been adequately investigated so far, we compared outcomes of patients receiving cabazitaxel with or without daily corticosteroids in a retrospective single-Institution cohort of mCRPC patients...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28915573/lipid-catabolism-inhibition-sensitizes-prostate-cancer-cells-to-antiandrogen-blockade
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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