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Treatment resistant mCRPC

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https://www.readbyqxmd.com/read/28096932/contemporary-agents-in-the-management-of-metastatic-castration-resistant-prostate-cancer
#1
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/28074331/a-retrospective-analysis-of-the-first-41-mcrpc-patients-with-bone-pain-treated-with-radium-223-at-the-national-institute-of-oncology-in-hungary
#2
Zs Küronya, I Sinkovics, P Ágoston, K Bíró, I Bodrogi, I Böde, M Dank, F Gyergyay, T Vajdics, Zs Kolonics, K Nagyiványi, Á Rúzsa, L Géczi
Radium-223 dichloride is an alpha-emitting radiopharmaceutical which significantly prolongs overall survival in patients with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases. This was a retrospective analysis of the efficacy and safety of Radium-223 in the first 41 patients treated at a single center in Hungary. Radium-223 was given at a dose of 50 kBq/kg intravenously every 4 weeks for up to 6 cycles. Between 23rd July 2014 and 23rd February 2016, 41 patients were treated. Patient demographics, laboratory values, treatment outcomes and adverse events were collected from medical records...
January 10, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28068151/prognostic-impact-of-pretreatment-neutrophil-to-lymphocyte-ratio-in-castration-resistant-prostate-cancer-patients-treated-with-first-line-docetaxel
#3
Consuelo Buttigliero, Chiara Pisano, Marcello Tucci, Francesca Vignani, Valentina Bertaglia, Davide Iaconis, Pamela Guglielmini, Gianmauro Numico, Giorgio V Scagliotti, Massimo Di Maio
BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR), a measure of systemic inflammatory response, has been associated with poor outcome in several solid tumors, including prostate cancer. We retrospectively investigated the prognostic role of pretreatment NLR in metastatic castration-resistant prostate cancer (mCRPC) patients treated with first-line docetaxel. METHODS: All CRPC patients treated with first-line docetaxel at two Italian institutions, with available data about baseline neutrophil and lymphocyte values, were included in this retrospective analysis...
January 9, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28067867/germline-brca2-mutations-drive-prostate-cancers-with-distinct-evolutionary-trajectories
#4
Renea A Taylor, Michael Fraser, Julie Livingstone, Shadrielle Melijah G Espiritu, Heather Thorne, Vincent Huang, Winnie Lo, Yu-Jia Shiah, Takafumi N Yamaguchi, Ania Sliwinski, Sheri Horsburgh, Alice Meng, Lawrence E Heisler, Nancy Yu, Fouad Yousif, Melissa Papargiris, Mitchell G Lawrence, Lee Timms, Declan G Murphy, Mark Frydenberg, Julia F Hopkins, Damien Bolton, David Clouston, John D McPherson, Theodorus van der Kwast, Paul C Boutros, Gail P Risbridger, Robert G Bristow
Germline mutations in the BRCA2 tumour suppressor are associated with both an increased lifetime risk of developing prostate cancer (PCa) and increased risk of aggressive disease. To understand this aggression, here we profile the genomes and methylomes of localized PCa from 14 carriers of deleterious germline BRCA2 mutations (BRCA2-mutant PCa). We show that BRCA2-mutant PCa harbour increased genomic instability and a mutational profile that more closely resembles metastastic than localized disease. BRCA2-mutant PCa shows genomic and epigenomic dysregulation of the MED12L/MED12 axis, which is frequently dysregulated in metastatic castration-resistant prostate cancer (mCRPC)...
January 9, 2017: Nature Communications
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
#5
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
#6
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/28053513/metastatic-castration-resistant-prostate-cancer-in-very-elderly-patients-challenges-and-solutions
#7
REVIEW
Orazio Caffo, Francesca Maines, Mimma Rizzo, Stefania Kinspergher, Antonello Veccia
The treatment of elderly patients with cancer is usually viewed by clinicians as a challenge, because of the age-related decline in normal organ function and the frequent concomitant administration of multiple drugs for comorbid conditions. Clinicians therefore tend not to prescribe antineoplastic agents (mainly in the case of chemotherapy) to elderly patients, with the fear of excess toxicity leading to an unfavorable cost:benefit ratio. The cutoff age defining a cancer patient as elderly is usually 70 years, but over the last 10 years clinicians have paid more attention to functional status, as evaluated by means of a comprehensive geriatric assessment and comorbidity burden, rather than chronological age...
2017: Clinical Interventions in Aging
https://www.readbyqxmd.com/read/28047654/mo-ab-bra-05-18f-naf-pet-ct-imaging-biomarkers-in-metastatic-prostate-cancer
#8
S Harmon, T Perk, C Lin, J Eickhoff, P Choyke, W Dahut, A Apolo, J Humm, S Larson, M J Morris, S Perlman, G Liu, R Jeraj
PURPOSE: Clinical use of (18) F-Sodium Fluoride (NaF) PET/CT in metastatic settings often lacks technology to quantitatively measure full disease dynamics due to high tumor burden. This study assesses radiomics-based extraction of NaF PET/CT measures, including global metrics of overall burden and local metrics of disease heterogeneity, in metastatic prostate cancer for correlation to clinical outcomes. METHODS: Fifty-six metastatic Castrate-Resistant Prostate Cancer (mCRPC) patients had NaF PET/CT scans performed at baseline and three cycles into chemotherapy (N=16) or androgen-receptor (AR) inhibitors (N=39)...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28047036/we-fg-202-05-quantification-of-bone-flare-on-f-18-naf-pet-ct-in-metastatic-prostate-cancer
#9
A Weisman, S Harmon, T Perk, M Scarpelli, G Liu, R Jeraj
PURPOSE: Bone flare has been observed on Tc-99m bone scans during early assessment in metastatic Castration-Resistant Prostate Cancer (mCRPC) patients receiving select androgen-signaling pathway (AR) targeted treatments, including CYP17-inhibitor Abiraterone. This study investigates the appearance and potential clinical impact of bone flare in mCRPC patients receiving CYP17-inhibitors using (18) F-NaF PET/CT. METHODS: Twenty-three mCRPC patients being treated with CYP17-inhibitors received NaF PET/CT scans at baseline, week 6, and week 12 of treatment...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28039155/phase-i-ii-trial-of-cabazitaxel-plus-abiraterone-in-patients-with-metastatic-castration-resistant-prostate-cancer-mcrpc-progressing-after-docetaxel-and-abiraterone
#10
C Massard, J Mateo, Y Loriot, C Pezaro, L Albiges, N Mehra, A Varga, D Bianchini, C J Ryan, D P Petrylak, G Attard, L Shen, K Fizazi, J de Bono
BACKGROUND: Abiraterone and cabazitaxel improve survival in patients with metastatic castration-resistant prostate cancer (mCRPC). We conducted an open-label phase I/II trial of cabazitaxel plus abiraterone to assess the antitumor activity and tolerability in patients with progressive mCRPC after docetaxel (phase I), and after docetaxel and abiraterone (phase II) (NCT01511536). PATIENTS AND METHODS: The primary objectives were to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of cabazitaxel plus abiraterone (phase I), and the prostate-specific antigen (PSA) response defined as a ≥ 50% decrease confirmed ≥3 weeks later with this combination (phase II)...
October 18, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28038931/safety-of-same-day-pegfilgrastim-administration-in-metastatic-castration-resistant-prostate-cancer-treated-with-cabazitaxel-with-or-without-carboplatin
#11
Mehmet Asim Bilen, Diana H Cauley, Bradley J Atkinson, Hsiang-Chun Chen, Diana H Kaya, Xuemei Wang, Raghu Vikram, Shi-Ming Tu, Paul G Corn, Jeri Kim
INTRODUCTION: Although myeloid growth factors are commonly used to treat metastatic castration-resistant prostate cancer (mCRPC), the optimal timing of administration has not been well studied. We assessed the effects of same-day pegfilgrastim, a neutrophil stimulator, after cabazitaxel treatment with or without carboplatin in patients with mCRPC. We also evaluated the frequency of urinary tract inflammation during treatment. PATIENTS AND METHODS: Between September 2010 and September 2014, 151 consecutive patients with mCRPC underwent cabazitaxel treatment with or without the addition of carboplatin at a single institution...
December 13, 2016: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28027708/re-emergence-of-an-orphan-therapeutic-target-for-the-treatment-of-resistant-prostate-cancer-a-thorough-conformational-and-binding-analysis-for-ror-%C3%AE-protein
#12
Umar Ndagi, Ndumiso N Mhlongo, Mahmoud E Soliman
Recent studies have linked a deadly form of prostate cancer known as metastatic castration-resistant prostate cancer (mCRPC) to retinoic acid-related orphan-receptor gamma (ROR-γ). Most of these studies continued to place ROR-γ as orphan because of unidentifiable inhibitor. Recently identified inhibitors of ROR-γ and their therapeutic potential were evaluated, among which inhibitor XY018 was the potent. However, molecular understanding of the conformational features of XY018-ROR-γ complex is still elusive...
December 28, 2016: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28027516/relation-between-plasma-trough-concentration-of-abiraterone-and-prostate-specific-antigen-response-in-metastatic-castration-resistant-prostate-cancer-patients
#13
E Carton, G Noe, O Huillard, L Golmard, J Giroux, A Cessot, N E B Saidu, M Peyromaure, M Zerbib, C Narjoz, J Guibourdenche, A Thomas, M Vidal, F Goldwasser, B Blanchet, J Alexandre
BACKGROUND: Abiraterone (ABI) is a major oral agent for the treatment of metastatic castration-resistant prostate cancer (mCRPC) patients but its systemic exposure is subject to a large inter-individual variability. We aimed to explore the relationship between ABI trough plasma concentration and prostate-specific antigen (PSA) response in mCRPC patients and to identify the critical determinants for its activity. PATIENTS AND METHODS: This is a monocentric prospective observational study in mCRPC patients treated with ABI...
December 24, 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/28026865/factors-predicting-skeletal-related-events-in-patients-with-bone-metastatic-castration-resistant-prostate-cancer
#14
Zachary Klaassen, Lauren E Howard, Amanda de Hoedt, Christopher L Amling, William J Aronson, Matthew R Cooperberg, Christopher J Kane, Martha K Terris, Stephen J Freedland
BACKGROUND: Skeletal-related events (SREs) are common complications of bone metastatic castration-resistant prostate cancer (mCRPC). To the authors' knowledge, there are limited data regarding which factors predict SREs. The authors identified risk factors for SREs in men with bone mCRPC using characteristics commonly available in the medical record. METHODS: Data from 454 patients with nonmetastatic CRPC were identified from 2 Veteran Affairs Medical Centers from 2000 through 2013...
December 27, 2016: Cancer
https://www.readbyqxmd.com/read/28008755/an-exploratory-analysis-of-the-association-between-levels-of-hormones-implied-in-steroid-biosynthesis-and-activity-of-abiraterone-in-patients-with-metastatic-castration-resistant-prostate-cancer
#15
Valentina Bertaglia, Marcello Tucci, Francesca Vignani, Consuelo Buttigliero, Emiliano Aroasio, Alfredo Berruti, Giorgio V Scagliotti, Massimo DI Maio
BACKGROUND: Abiraterone acetate, approved for patients with metastatic castration-resistant prostate cancer (mCRPC), blocks androgen byosinthesis. We aimed to describe changes determined by abiraterone in hormones implied in steroid biosynthesis, exploring association between hormonal levels and drug activity. METHODS: Patients with mCRPC, receiving standard abiraterone + prednisone after docetaxel failure, were studied. We determined serum levels of progesterone, 17OH-progesterone, cortisol, ACTH, DHEA-sulphate, androstenedione, testosterone, sex hormone-binding globulin, aldosterone, plasma renin activity, and cholesterol, baseline and every 12 weeks...
December 22, 2016: Minerva Urologica e Nefrologica, the Italian Journal of Urology and Nephrology
https://www.readbyqxmd.com/read/27990667/clinical-correlates-of-benefit-from-radium-223-therapy-in-metastatic-castration-resistant-prostate-cancer
#16
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/27990267/two-step-feature-selection-for-predicting-survival-time-of-patients-with-metastatic-castrate-resistant-prostate-cancer
#17
Motoki Shiga
Metastatic castrate resistant prostate cancer (mCRPC) is the major cause of death in prostate cancer patients. Even though some options for treatment of mCRPC have been developed, the most effective therapies remain unclear. Thus finding key patient clinical variables related with mCRPC is an important issue for understanding the disease progression mechanism of mCRPC and clinical decision making for these patients. The Prostate Cancer DREAM Challenge is a crowd-based competition to tackle this essential challenge using new large clinical datasets...
2016: F1000Research
https://www.readbyqxmd.com/read/27981431/adjusting-overall-survival-estimates-after-treatment-switching-a-case-study-in-metastatic-castration-resistant-prostate-cancer
#18
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/27979426/nuclear-specific-ar-v7-protein-localization-is-necessary-to-guide-treatment-selection-in-metastatic-castration-resistant-prostate-cancer
#19
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/27960186/cabazitaxel-in-metastatic-castration-resistant-prostate-cancer-patients-progressing-after-docetaxel-a-prospective-single-center-study
#20
Giuseppe Cicero, Rossella De Luca, Patrizia Dorangricchia, Antonio Galvano, Giuseppe Lo Re, Vincenzo Serretta, Nino Dispensa, Francesco Dieli
PURPOSE: The present study aims to evaluate the efficacy of cabazitaxel in combination with prednisone treatment in Italian patients affected by hormone-refractory metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel plus prednisone. METHODS: Thirty patients with mCRPC were enrolled between June 2013 and January 2016 (the last follow-up was in January 2016). Cabazitaxel was used according to the summary of product characteristics and administered at a dose of 25 mg/m2 every 3 weeks plus oral prednisone at a dose of 5-mg tablets twice a day continuously...
December 14, 2016: Oncology
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