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https://www.readbyqxmd.com/read/29453313/multigene-profiling-of-ctcs-in-mcrpc-identifies-a-clinically-relevant-prognostic-signature
#1
Udit Singhal, Yugang Wang, James Henderson, Yashar S Niknafs, Yuanyuan Qiao, Amy Gursky, Alexander Zaslavsky, Jae-Seung Chung, David C Smith, R Jeffrey Karnes, S Laura Chang, Felix Y Feng, Ganesh S Palapattu, Russell S Taichman, Arul M Chinnaiyan, Scott A Tomlins, Todd M Morgan
The trend towards precision-based therapeutic approaches dictated by molecular alterations offers substantial promise for men with metastatic castration resistant prostate cancer (mCRPC). However, current approaches for molecular characterization are primarily tissue based, necessitating serial biopsies to understand changes over time and are limited by the challenges inherent to extracting genomic material from predominantly bone metastases. Therefore, a circulating tumor cell (CTC)-based assay was developed to determine gene expression across a panel of clinically relevant and potentially actionable prostate cancer related genes...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29439820/germline-dna-repair-gene-mutations-and-outcomes-in-men-with-metastatic-castration-resistant-prostate-cancer-receiving-first-line-abiraterone-and-enzalutamide
#2
Emmanuel S Antonarakis, Changxue Lu, Brandon Luber, Chao Liang, Hao Wang, Yan Chen, John L Silberstein, Danilo Piana, Zhao Lai, Yidong Chen, William B Isaacs, Jun Luo
BACKGROUND: Inherited DNA-repair gene mutations are more prevalent in men with advanced prostate cancer than previously thought, but their clinical implications are not fully understood. OBJECTIVE: To investigate the clinical significance of germline DNA-repair gene alterations in men with metastatic castration-resistant prostate cancer (mCRPC) receiving next-generation hormonal therapy (NHT), with a particular emphasis on BRCA/ATM mutations. DESIGN, SETTING, AND PARTICIPANTS: We interrogated 50 genes for pathogenic or likely pathogenic germline mutations using leukocyte DNA from 172 mCRPC patients beginning treatment with first-line NHT with abiraterone or enzalutamide...
February 10, 2018: European Urology
https://www.readbyqxmd.com/read/29431540/pharmacokinetic-pharmacodynamic-drug-evaluation-of-enzalutamide-for-treating-prostate-cancer
#3
Jeong Hee Hong
Enzalutamide is the first approved second-generation androgen receptor (AR) antagonist in the treatment of metastatic castration-resistant prostate cancer (mCRPC) with or without docetaxel-based chemotherapy. Over the past 5 years, a number of attempts were made to determine the efficacy of enzalutamide in the different clinical settings. Areas covered: A literature search was performed at the PubMed, Embase, and Web of Science database to collect the most relevant and impactful studies, including basic science investigations, clinical trials, and reviews...
February 12, 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29431193/circulating-tumor-cells-and-survival-in-abiraterone-and-enzalutamide-treated-patients-with-castration-resistant-prostate-cancer
#4
Bram De Laere, Steffi Oeyen, Peter Van Oyen, Christophe Ghysel, Jozef Ampe, Piet Ost, Wim Demey, Lucien Hoekx, Dirk Schrijvers, Barbara Brouwers, Willem Lybaert, Els Everaert, Piet Van Kerckhove, Daan De Maeseneer, Michiel Strijbos, Alain Bols, Karen Fransis, Nick Beije, Inge de Kruijff, Valerie van Dam, Anja Brouwer, Pieter-Jan van Dam, Gert Van den Eynden, Annemie Rutten, Stefan Sleijfer, Jean Vandebroek, Steven Van Laere, Luc Dirix
BACKGROUND: The outcome to treatment administered to patients with metastatic castration-resistant prostate cancer (mCRPC) greatly differs between individuals, underlining the need for biomarkers guiding treatment decision making. OBJECTIVE: To investigate the prognostic value of circulating tumor cell (CTC) enumeration and dynamics, in the context of second-line endocrine therapies (ie, abiraterone acetate or enzalutamide), irrespective of prior systemic therapies...
February 12, 2018: Prostate
https://www.readbyqxmd.com/read/29419479/the-effect-of-total-tumor-volume-on-the-biologically-effective-dose-of-tumor-and-kidneys-for-177lu-labelled-psma-peptides
#5
Nusrat Begum, Anne Thieme, Nina Eberhardt, Robert Tauber, Ambros J Beer, Gerhard Glatting, Matthias Eiber, Peter Kletting
Aim: To simulate the effect of PSMA positive total tumor volume (TTV) on the tumor and organs at risk (OARs) biologically effective doses (BEDs) in patients with metastatic castration resistant prostate cancer (mCRPC) in 177Lu-PSMA radioligand therapy. Methods: A physiologically-based pharmacokinetic model was fitted to data of 13 patients treated with 177Lu-PSMA I&T. The tumor, kidneys and salivary glands BEDs were simulated for TTVs of 0.1-10 l. The activity and peptide amounts leading to an optimal tumor-to-kidneys BED ratio were also investigated...
February 1, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29402534/association-among-metabolic-syndrome-inflammation-and-survival-in-prostate-cancer
#6
Vincenza Conteduca, Orazio Caffo, Luca Galli, Antonio Maugeri, Emanuela Scarpi, Francesca Maines, Vincenzo Emanuele Chiuri, Cristian Lolli, Stefania Kinspergher, Giuseppe Schepisi, Matteo Santoni, Daniele Santini, Lucia Fratino, Salvatore Luca Burgio, Samanta Salvi, Cecilia Menna, Ugo De Giorgi
BACKGROUND: Metabolic syndrome (MS) and inflammation (INF) alterations are among the factors involved in cancer progression. The study aimed to assess the relationship between MS and INF and its effect on progression-free/overall survival (PFS/OS) in metastatic castration-resistant prostate cancer (mCRPC) treaed with abiraterone or enzalutamide. METHODS: We, retrospectively, evaluated patients with mCRPC in 7 Italian Institutes between March 2011 and October 2016...
February 2, 2018: Urologic Oncology
https://www.readbyqxmd.com/read/29398263/expression-of-androgen-receptor-splice-variant-7-or-9-in-whole-blood-does-not-predict-response-to-androgen-axis-targeting-agents-in-metastatic-castration-resistant-prostate-cancer
#7
Sarah Q To, Edmond M Kwan, Heidi C Fettke, Andrew Mant, Maria M Docanto, Luciano Martelotto, Patricia Bukczynska, Nicole Ng, Lisa-Jane K Graham, Phillip Parente, Carmel Pezaro, Kate Mahon, Lisa Horvath, Tilman Todenhöfer, Arun A Azad
In 2014, a landmark study was published demonstrating that the expression of androgen receptor splice variant (AR-V) 7 was a negative predictive biomarker for response to abiraterone acetate and enzalutamide in metastatic castration-resistant prostate cancer (mCRPC) patients. However, these results were not supported by the recently reported ARMOR3-SV phase III clinical trial, which employed an identical circulating tumour cell assay to assess AR-V7 expression. Therefore, the predictive utility of AR-V7 expression in mCRPC remains uncertain, as does any potential association between other AR-Vs and treatment response...
February 2, 2018: European Urology
https://www.readbyqxmd.com/read/29388415/innovations-in-imaging-modalities-for-recurrent-and-metastatic-prostate-cancer-a-systematic-review
#8
Simone Albisinni, Fouad Aoun, Quentin Marcelis, Claude Jungels, Walid Al Hajj Obeid, Marc Zanaty, Andrea Tubaro, Thierry Roumeguere, Cosimo DE Nunzio
INTRODUCTION: The last decade has witnessed tremendous changes in the management of advanced and metastatic castration resistant prostate cancer (mCRPC). In the current systematic review, we analyze novel imaging techniques in the setting of recurrent and metastatic PCa, exploring available data and highlighting future exams which could enter clinical practice in the upcoming years. EVIDENCE ACQUISITION: The National Library of Medicine Database was searched for relevant articles published between January 2012 and August 2017...
January 31, 2018: Minerva Urologica e Nefrologica, the Italian Journal of Urology and Nephrology
https://www.readbyqxmd.com/read/29388324/taxane-chemotherapy-versus-anti-androgen-agents-as-first-line-therapy-for-metastatic-castration-resistant-prostate-cancer
#9
Guru Sonpavde, Ahong Huang, Li Wang, Onur Baser, Raymond Miao
OBJECTIVES: To assess treatment patterns and outcomes of patients with metastatic castration-resistant prostate cancer (mCRPC) receiving first-line chemotherapy or anti-androgen therapy. PATIENTS AND METHODS: Patients initiating first-line anti-androgen therapy (abiraterone, enzalutamide) or chemotherapy (taxane) from Oct/2012-Sept/2014 were retrospectively identified in the US Veterans Health Administration (VHA) database. The impact of anti-androgen therapy versus chemotherapy on overall survival (OS) and time to discontinuation was assessed using Cox proportional hazard models, adjusting for prior androgen deprivation therapy (ADT) duration and available prognostic factors...
February 1, 2018: BJU International
https://www.readbyqxmd.com/read/29381456/a-prognostic-model-for-stratifying-clinical-outcomes-in-chemotherapy-naive-metastatic-castration-resistant-prostate-cancer-patients-treated-with-abiraterone-acetate
#10
D J Khalaf, C M Avilés, A A Azad, K Sunderland, T Todenhöfer, B J Eigl, D Finch, L Le, A Atwell, B Keith, C Kollmannsberger, K N Chi
INTRODUCTION: Recently, a prognostic index including six risk factors (RFs) (unfavourable ECOG performance status [PS], presence of liver metastases, short response to luteinizing hormone-releasing hormone [LHRH] agonists/antagonists, low albumin, increased alkaline phosphatase [ALP] and lactate dehydrogenase [LDH]) was developed from the COU-AA-301 trial in post-chemotherapy metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone acetate. Our primary objective was to evaluate this model in a cohort of chemotherapy-naive mCRPC patients receiving abiraterone...
December 1, 2017: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
https://www.readbyqxmd.com/read/29367197/circulating-tumor-dna-genomics-correlate-with-resistance-to-abiraterone-and-enzalutamide-in-prostate-cancer
#11
Matti Annala, Gillian Vandekerkhove, Daniel Khalaf, Sinja Taavitsainen, Kevin Beja, Evan W Warner, Katherine Sunderland, Christian Kollmannsberger, Bernhard J Eigl, Daygen Finch, Conrad D Oja, Joanna Vergidis, Muhammad Zulfiqar, Arun A Azad, Matti Nykter, Martin E Gleave, Alexander W Wyatt, Kim N Chi
Primary resistance to androgen receptor (AR) directed therapies in metastatic castration-resistant prostate cancer (mCRPC) is poorly understood. We randomized 202 treatment-naive mCRPC patients to abiraterone or enzalutamide, and performed whole exome and deep targeted 72-gene sequencing of plasma cell-free DNA prior to therapy. For these agents, which have never been directly compared, time to progression was similar. Defects in BRCA2 and ATM were strongly associated with poor clinical outcomes independently of clinical prognostic factors and circulating tumor DNA abundance...
January 24, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29352714/effect-of-single-agent-daily-prednisone-on-outcomes-and-toxicities-in-metastatic-castration-resistant-prostate-cancer-pooled-analysis-of-prospective-studies
#12
REVIEW
Pooja Ghatalia, Gregory R Pond, Arnoud J Templeton, Guru Sonpavde
The clinical effect of prednisone in metastatic castration-resistant prostate cancer (mCRPC) is unknown. We performed a pooled analysis of control arms of randomized controlled trials that had or had not administered single-agent prednisone. Randomized controlled trials with a control arm that included single-agent placebo (or no anticancer therapy) or single-agent prednisone (with or without placebo) were eligible for analysis. Patients receiving prednisone combined with other agents in the control arm were excluded...
December 27, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29352713/clinical-variables-associated-with-overall-survival-in-metastatic-castration-resistant-prostate-cancer-patients-treated-with-sipuleucel-t-immunotherapy
#13
Xiao X Wei, Jaselle Perry, Emily Chang, Li Zhang, Robert A Hiatt, Charles J Ryan, Eric J Small, Lawrence Fong
BACKGROUND: Sipuleucel-T is an autologous cell-based cancer immunotherapy for men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). Its approval by the Food and Drug Administration was based on demonstration of an overall survival (OS) benefit in randomized placebo-controlled phase III trials. However, treatment was associated with a prostate-specific antigen (PSA) decline in only a small minority of patients. Understanding the clinical factors that are associated with OS could help guide treatment decisions, including patient selection and the timing of sipuleucel-T relative to other therapies...
December 27, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29340285/quantitative-bone-scan-lesion-area-as-an-early-surrogate-outcome-measure-indicative-of-overall-survival-in-metastatic-prostate-cancer
#14
Matthew S Brown, Grace Hyun J Kim, Gregory H Chu, Bharath Ramakrishna, Martin Allen-Auerbach, Cheryce P Fischer, Benjamin Levine, Pawan K Gupta, Christiaan W Schiepers, Jonathan G Goldin
A clinical validation of the bone scan lesion area (BSLA) as a quantitative imaging biomarker was performed in metastatic castration-resistant prostate cancer (mCRPC). BSLA was computed from whole-body bone scintigraphy at baseline and week 12 posttreatment in a cohort of 198 mCRPC subjects (127 treated and 71 placebo) from a clinical trial involving a different drug from the initial biomarker development. BSLA computation involved automated image normalization, lesion segmentation, and summation of the total area of segmented lesions on bone scan AP and PA views as a measure of tumor burden...
January 2018: Journal of Medical Imaging
https://www.readbyqxmd.com/read/29340049/pharmacological-treatment-with-inhibitors-of-nuclear-export-enhances-the-antitumor-activity-of-docetaxel-in-human-prostate-cancer
#15
Giovanni Luca Gravina, Andrea Mancini, Alessandro Colapietro, Francesco Marampon, Roberta Sferra, Simona Pompili, Leda Assunta Biordi, Roberto Iorio, Vincenzo Flati, Christian Argueta, Yosef Landesman, Michael Kauffman, Sharon Shacham, Claudio Festuccia
Background and aims: Docetaxel (DTX) modestly increases patient survival of metastatic castration-resistant prostate cancer (mCRPC) due to insurgence of pharmacological resistance. Deregulation of Chromosome Region Maintenance (CRM-1)/ exportin-1 (XPO-1)-mediated nuclear export may play a crucial role in this phenomenon. Material and methods: Here, we evaluated the effects of two Selective Inhibitor of Nuclear Export (SINE) compounds, selinexor (KPT-330) and KPT-251, in association with DTX by using 22rv1, PC3 and DU145 cell lines with their...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29334610/phase-ii-study-of-dovitinib-in-patients-with-castration-resistant-prostate-cancer-kcsg-gu11-05
#16
Yoon Ji Choi, Hye Sook Kim, Se Hoon Park, Bong-Seog Kim, Kyoung Ha Kim, Hyo Jin Lee, Hong Suk Song, Dong-Yeop Shin, Ha Young Lee, Hoon-Gu Kim, Kyung Hee Lee, Jae Lyun Lee, Kyong Hwa Park
Purpose: Fibroblast growth factor (FGF) signals are important in carcinogenesis and progression of prostate cancer. Dovitinib is an oral, pan-class inhibitor of vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, and fibroblast growth factor receptor (FGFR). We evaluated the efficacy and toxicity of dovitinib in men with metastatic castration resistant prostate cancer (mCRPC). Materials and Methods: This study was a single-arm, phase II, open-label, multicenter trial of dovitinib 500mg/day (5-days-on/2-days-off schedule)...
January 2, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29331381/clinical-outcomes-of-first-line-abiraterone-acetate-or-enzalutamide-for-metastatic-castration-resistant-prostate-cancer-after-androgen-deprivation-therapy%C3%A2-docetaxel-or-adt-alone-for-metastatic-hormone-sensitive-prostate-cancer
#17
Edoardo Francini, Steven Yip, Shubidito Ahmed, Haocheng Li, Luke Ardolino, Carolyn P Evan, Marina Kaymakcalan, Grace K Shaw, Philip W Kantoff, Mary-Ellen Taplin, Nimira S Alimohamed, Anthony M Joshua, Daniel Y C Heng, Christopher J Sweeney
BACKGROUND: The CHAARTED (ChemoHormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer) and STAMPEDE (Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy) trials showed that the addition of docetaxel (D) to androgen deprivation therapy (ADT) prolonged longevity of men with metastatic hormone-sensitive prostate cancer (mHSPC). However, the impact of upfront D on subsequent therapies is still unexplored. As abiraterone acetate (AA) and enzalutamide (E) are the most commonly used first-line treatment for metastatic castration-resistant prostate cancer (mCRPC), we aimed to assess whether they maintained their efficacy after ADT+D versus ADT alone...
December 27, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29327812/hyper-acetylation-contributes-to-the-sensitivity-of-chemo-resistant-prostate-cancer-cells-to-histone-deacetylase-inhibitor-trichostatin-a
#18
Qingqing Xu, Xiaofei Liu, Shiqin Zhu, Xuelei Hu, Huanmin Niu, Xiulei Zhang, Deyu Zhu, Effat Un Nesa, Keli Tian, Huiqing Yuan
Therapeutic agents are urgently needed for treating metastatic castration-refractory prostate cancer (mCRPC) that is unresponsive to androgen deprivation and chemotherapy. Our screening assays demonstrated that chemotherapy-resistant prostate cancer (PCa) cells are more sensitive to HDAC inhibitors than paired sensitive PCa cells, as demonstrated by cell proliferation and apoptosis in vitro and in vivo. Kinetic study revealed that TSA-induced apoptosis was significantly dependent on enhanced transcription and protein synthesis in an early stage, which subsequently caused ER stress and apoptosis...
January 12, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29326358/targeted-alpha-therapy-of-mcrpc-with-225actinium-psma-617-swimmer-plot-analysis-suggests-efficacy-regarding-duration-of-tumor-control
#19
Clemens Kratochwil, Frank Bruchertseifer, Hendrik Rathke, Markus Hohenfellner, Frederik L Giesel, Uwe Haberkorn, Alfred Morgenstern
The aim of this evaluation is to identify first indicators regarding the efficacy of 225Ac-PSMA-617 therapy in a retrospectively analyzed group of patients. Methods: Forty patients with metastatic castration-resistant prostate cancer were selected for treatment with 3 cycles of 100 kBq/kgBW 225Ac-PSMA-617 in 2 months intervals. Prostate-specific antigen (PSA) and blood cell count were measured every 4 weeks. Prostate-specific membrane antigen (PSMA)-PET/CT or PSMA-SPECT/CT were used for baseline staging and imaging follow-up at month six...
January 11, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29319382/ctc-derived-ar-v7-detection-as-a-prognostic-and-predictive-biomarker-in-advanced-prostate-cancer
#20
Diogo A Bastos, Emmanuel S Antonarakis
Prostate cancer is a highly heterogeneous disease, with remarkably different prognosis across all stages. Increased circulating tumor cell (CTC) count (≥ 5) using the CellSearch assay has been identified as one of the markers that can be used to predict survival, with added value beyond currently available prognostic factors. Recently, androgen receptor splice variant 7 (AR-V7) detection has been associated with worse outcomes for patients with castration-resistant prostate cancer (CRPC) treated with novel androgen receptor-signaling (ARS) inhibitors such as abiraterone and enzalutamide but not taxane chemotherapies...
January 10, 2018: Expert Review of Molecular Diagnostics
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