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Treatment resistant mCRPC

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https://www.readbyqxmd.com/read/29781343/issues-and-promises-of-bevacizumab-in-prostate-cancer-treatment
#1
Vittore Cereda, Vincenzo Formica, Mario Roselli
There is general agreement that increased angiogenesis is an important factor in determining prostate cancer development and prognosis. Vascular Endothelial Growth Factor (VEGF) is thought to play a primary role in the molecular events that lead to prostate cancer progression, from androgen-dependency to castration-resistance until dissemination to the skeleton. Bevacizumab is a recombinant anti-VEGF monoclonal antibody that has exhibited clinical activity in different cancer types. Areas covered: In this review we summarize the data of clinical trials, investigating the effects of bevacizumab in prostate cancer patients...
May 21, 2018: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/29778323/is-there-a-flare-phenomenon-on-bone-scintigraphy-in-men-with-advanced-prostate-cancer-treated-with-radium-223
#2
Gesa Isensee, Anne Péporté, Joachim Müller, Sabine Schmid, Silke Gillessen, Aurelius Omlin
INTRODUCTION: Radium-223 is an approved survival-prolonging treatment option in men with castration-resistant prostate cancer (mCRPC) and bone metastases. In the registration trial (ALSYMPCA), no regular imaging was mandated. We aimed to analyze men with metastatic mCRPC treated with radium-223 who had bone scintigraphy for staging and treatment monitoring. PATIENTS AND METHODS: Retrospective chart review was performed of mCRPC patients who received 6 cycles of radium-223 and who underwent bone scintigraphy before start of radium-223 and after 3 and 6 cycles of treatment...
April 23, 2018: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29764892/intense-exercise-for-survival-among-men-with-metastatic-castrate-resistant-prostate-cancer-interval-gap4-a-multicentre-randomised-controlled-phase-iii-study-protocol
#3
Robert U Newton, Stacey A Kenfield, Nicolas H Hart, June M Chan, Kerry S Courneya, James Catto, Stephen P Finn, Rosemary Greenwood, Daniel C Hughes, Lorelei Mucci, Stephen R Plymate, Stephan F E Praet, Emer M Guinan, Erin L Van Blarigan, Orla Casey, Mark Buzza, Sam Gledhill, Li Zhang, Daniel A Galvão, Charles J Ryan, Fred Saad
INTRODUCTION: Preliminary evidence supports the beneficial role of physical activity on prostate cancer outcomes. This phase III randomised controlled trial (RCT) is designed to determine if supervised high-intensity aerobic and resistance exercise increases overall survival (OS) in patients with metastatic castrate-resistant prostate cancer (mCRPC). METHODS AND ANALYSIS: Participants (n=866) must have histologically documented metastatic prostate cancer with evidence of progressive disease on androgen deprivation therapy (defined as mCRPC)...
May 14, 2018: BMJ Open
https://www.readbyqxmd.com/read/29757368/the-long-noncoding-rna-landscape-of-neuroendocrine-prostate-cancer-and-its-clinical-implications
#4
Varune Rohan Ramnarine, Mohammed Alshalalfa, Fan Mo, Noushin Nabavi, Nicholas Erho, Mandeep Takhar, Robert Shukin, Sonal Brahmbhatt, Alexander Gawronski, Maxim Kobelev, Mannan Nouri, Dong Lin, Harrison Tsai, Tamara L Lotan, R Jefferey Karnes, Mark A Rubin, Amina Zoubeidi, Martin E Gleave, Cenk Sahinalp, Alexander W Wyatt, Stanislav V Volik, Himisha Beltran, Elai Davicioni, Yuzhuo Wang, Colin C Collins
Background: Treatment induced neuroendocrine prostate cancer (tNEPC) is an aggressive variant of late-stage metastatic castrate resistant (mCRPC) prostate cancer that commonly arises through neuroendocrine transdifferentiation (NEtD). Treatment options are limited, ineffective, and for most patients, results in death in less than a year. We previously developed a first-in-field patient-derived xenograft (PDX) model of NEtD. Longitudinal deep transcriptome profiling of this model enabled monitoring of dynamic transcriptional changes during NEtD and in the context of androgen deprivation...
May 10, 2018: GigaScience
https://www.readbyqxmd.com/read/29731989/statin-use-and-survival-in-patients-with-metastatic-castration-resistant-prostate-cancer-treated-with-abiraterone-or-enzalutamide-after-docetaxel-failure-the-international-retrospective-observational-staben-study
#5
Jacob A Gordon, Carlo Buonerba, Gregory Pond, Daniel Crona, Silke Gillessen, Giuseppe Lucarelli, Sabrina Rossetti, Tanya Dorff, Salvatore Artale, Jennifer A Locke, Davide Bosso, Matthew Ivan Milowsky, Mira Sofie Witek, Michele Battaglia, Sandro Pignata, Cyrus Cherhroudi, Michael E Cox, Pietro De Placido, Dario Ribera, Aurelius Omlin, Gaetano Buonocore, Kim Chi, Christian Kollmannsberger, Daniel Khalaf, Gaetano Facchini, Guru Sonpavde, Sabino De Placido, Bernhard J Eigl, Giuseppe Di Lorenzo
Background: Statins may potentiate the effects of anti-hormonal agents for metastatic castration-resistant prostate cancer (mCRPC) through further disruption of essential steroidogenic processes. We investigated the effects of statin use on clinical outcomes in patients with mCRPC receiving abiraterone or enzalutamide. Materials and methods: This was a retrospective multicenter study including patients that received abiraterone or enzalutamide for mCRPC. The effect of concurrent statin use on outcomes was evaluated...
April 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29716525/prognostic-value-of-an-automated-bone-scan-index-for-men-with-metastatic-castration-resistant-prostate-cancer-treated-with-cabazitaxel
#6
Koichi Uemura, Yasuhide Miyoshi, Takashi Kawahara, Jikuya Ryosuke, Daisuke Yamashita, Shuko Yoneyama, Yumiko Yokomizo, Kazuki Kobayashi, Takeshi Kishida, Masahiro Yao, Hiroji Uemura
BACKGROUND: A computer-assisted diagnostic system for analyzing bone scans (BONENAVI) calculates the automated bone scan index (aBSI). Here we evaluated the aBSI as a prognostic imaging biomarker for men with metastatic castration-resistant prostate cancer (mCRPC) treated with cabazitaxel. METHODS: We retrospectively analyzed 48 patients who received cabazitaxel for mCRPC and evaluated the ability of the aBSI to predict overall survival (OS). The Cox proportional hazards model was used to investigate the associations between baseline aBSI at cabazitaxel treatment and OS with the clinical variables as follows: age, number of cycles of docetaxel, serum prostate-specific antigen, hemoglobin (Hb), lactate dehydrogenase (LDH), and alkaline phosphatase...
May 2, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29700205/laboratory-based-biomarkers-and-liver-metastases-in-metastatic-castration-resistant-prostate-cancer
#7
Patrick M Cotogno, Lahiru K Ranasinghe, Elisa M Ledet, Brian E Lewis, Oliver Sartor
BACKGROUND: Metastatic castrate-resistant prostate cancer (mCRPC) patients with liver metastases have a poor prognosis. No large studies have investigated the clinical and biochemical parameters associated with liver metastases in this population. MATERIALS AND METHODS: Patient data made available via Project Data Sphere were collected from 1,281 men with mCRPC who were enrolled on to three phase III clinical trials for the treatment of their disease. Multiple logistic regression was performed on eight clinical and biochemical baseline variables to test their association with the presence of liver metastases on baseline radiographic imaging...
April 26, 2018: Oncologist
https://www.readbyqxmd.com/read/29688882/withdrawn-disparity-in-public-funding-of-therapies-for-metastatic-castrate-resistant-prostate-cancer-across-canadian-provinces
#8
Dixon T S Woon, Thenappan Chandrasekar, Lorne Aaron, Naveen S Basappa, Kim N Chi, Henry J Conter, Brita Danielson, Sebastien J Hotte, Shawn Malone, Fred Saad, Bobby Shayegan, Laura Park-Wyllie, Robert J Hamilton
Ahead of print article withdrawn by publisher.
April 12, 2018: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
https://www.readbyqxmd.com/read/29685343/weekly-versus-3-weekly-cabazitaxel-for-the-treatment-of-castration-resistant-prostate-cancer-a-randomised-phase-ii-trial-concab
#9
Jeffrey Yachnin, Bjørnar Gilje, Kristian Thon, Hemming Johansson, Yvonne Brandberg, Theocharis Panaretakis, Anders Ullén
AIM: Patients treated with cabazitaxel for metastatic castration-resistant prostate cancer (mCRPC) may experience dose delays and reductions or terminate treatment because of toxicity. A lower and more frequent dose of cabazitaxel could improve dose intensity. PATIENTS AND METHODS: This prospective, multi-center, phase II study randomly assigned 101 patients to Arm A, cabazitaxel Q3W, 25 mg/m2 or Arm B, Q1W, 10 mg/m2 5 of 6 weeks. The primary end-point was dose intensity, and we hypothesised that the experimental arm (Arm B) would result in a 20% absolute increase in the relative cumulative dose by week 18...
April 20, 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29684274/preclinical-development-of-novel-psma-targeting-radioligands-modulation-of-albumin-binding-properties-to-improve-prostate-cancer-therapy
#10
Christoph A Umbricht, Martina Benešová, Roger Schibli, Cristina Müller
The treatment of metastatic castration-resistant prostate cancer (mCRPC) remains challenging with current treatment options. The development of more effective therapies is, therefore, urgently needed. Targeted radionuclide therapy with prostate-specific membrane antigen (PSMA)-targeting ligands has revealed promising clinical results. In an effort to optimize this concept, it was the aim of this study to design and investigate PSMA ligands comprising different types of albumin binders. PSMA-ALB-53 and PSMA-ALB-56 were designed by combining the glutamate-urea-based PSMA-binding entity, a DOTA chelator and an albumin binder based on the 4-( p-iodophenyl)-moiety or p-(tolyl)-moiety...
May 2, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29673712/update-on-systemic-prostate-cancer-therapies-management-of-metastatic-castration-resistant-prostate-cancer-in-the-era-of-precision-oncology
#11
REVIEW
Philipp Nuhn, Johann S De Bono, Karim Fizazi, Stephen J Freedland, Maurizio Grilli, Philip W Kantoff, Guru Sonpavde, Cora N Sternberg, Srinivasan Yegnasubramanian, Emmanuel S Antonarakis
CONTEXT: Introduction of novel agents for the management of advanced prostate cancer provides a range of treatment options with notable benefits for men with metastatic castration-resistant prostate cancer (mCRPC). At the same time, understanding of optimal patient selection, effective sequential use, and development of resistance patterns remains incomplete. OBJECTIVE: To review current systemic therapies and recent advances in drug development for mCRPC and strategies to aid in patient selection and optimal sequencing...
April 16, 2018: European Urology
https://www.readbyqxmd.com/read/29656854/radical-prostatectomy-in-metastatic-castration-resistant-prostate-cancer-feasibility-safety-and-quality-of-life-outcomes
#12
Chad A Reichard, Justin R Gregg, Mary F Achim, Ana M Aparicio, Curtis A Pettaway, Louis L Pisters, John F Ward, John W Davis, Brian F Chapin
Ongoing prospective studies are evaluating treatment of the primary tumor in men with de novo metastatic prostate cancer (PCa). One potential benefit is prevention of morbidity from local progression. Thus, local therapy may be best applied selectively to men with local progression once resistance to first-line therapies has occurred. Here, we gather support for the hypothesis that radical prostatectomy (RP) is safe and preserves quality of life (QOL) when applied in men with metastatic castration-resistant PCa (mCRPC)...
April 12, 2018: European Urology
https://www.readbyqxmd.com/read/29651569/external-radiation-exposure-excretion-and-effective-half-life-in-177-lu-psma-targeted-therapies
#13
J Kurth, B J Krause, S M Schwarzenböck, L Stegger, M Schäfers, K Rahbar
BACKGROUND: Prostate-specific membrane antigen (PSMA)-targeted therapy with 177 Lu-PSMA-617 is a therapeutic option for patients with metastatic castration-resistant prostate cancer (mCRPC). To optimize the therapy procedure, it is necessary to determine relevant parameters to define radiation protection and safety necessities. Therefore, this study aimed at estimating the ambient radiation exposure received by the patient. Moreover, the excreted activity was quantified. RESULTS: In total, 50 patients with mCRPC and treated with 177 Lu-PSMA-617 (mean administered activity 6...
April 12, 2018: EJNMMI Research
https://www.readbyqxmd.com/read/29588330/onc201-targets-ar-and-ar-v7-signaling-reduces-psa-and-synergizes-with-everolimus-in-prostate-cancer
#14
Avital Lev, Amriti R Lulla, Brian C Ross, Marie D Ralff, Petr B Makhov, David T Dicker, Wafik S El-Deiry
Androgen receptor (AR) signaling plays a key role in prostate cancer progression, and androgen deprivation therapy (ADT) is a mainstay clinical treatment regimen for patients with advanced disease. Unfortunately, most prostate cancers eventually become androgen-independent and resistant to ADT with patients progressing to metastatic castration-resistant prostate cancer (mCRPC). Constitutively activated AR variants (AR-V) have emerged as mediators of resistance to AR-targeted therapy and the progression of mCRPC, and they represent an important therapeutic target...
March 27, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29574703/genomic-alterations-in-plasma-dna-from-patients-with-metastasized-prostate-cancer-receiving-abiraterone-or-enzalutamide
#15
Jelena Belic, Ricarda Graf, Thomas Bauernhofer, Yauheniya Cherkas, Peter Ulz, Julie Waldispuehl-Geigl, Samantha Perakis, Michael Gormley, Jaymala Patel, Weimin Li, Jochen B Geigl, Denis Smirnov, Ellen Heitzer, Mitchell Gross, Michael R Speicher
In patients with metastatic castrate resistant prostate cancer (mCRPC), circulating tumor DNA (ctDNA) analysis offers novel opportunities for the development of non-invasive biomarkers informative of treatment response with novel agents targeting the androgen-receptor (AR) pathway, such as abiraterone or enzalutamide. However, the relationship between ctDNA abundance, detectable somatic genomic alterations and clinical progression of mCRPC remains unexplored. Our study aimed to investigate changes in plasma DNA during disease progression and their associations with clinical variables in mCRPC patients...
March 25, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29565650/recent-advances-in-theranostics-and-challenges-for-the-future
#16
J Harvey Turner
Theranostic nuclear oncology is on the cusp of adoption into routine clinical management of neuroendocrine tumours (NETs) following publication of the Phase 3 randomised controlled trial, NETTER-1. For the first time, level 1b evidence of efficacy and safety of 68-gallium/177-lutetium-DOTA-octreotate peptide receptor radionuclide therapy, of mid-gut neuroendocrine tumours was established. Multicentre Phase 2 studies of 68-gallium/177-lutetium-prostate specific membrane antigen theranostic approaches to management of end-stage metastatic castrate-resistant prostate cancer, are also very encouraging...
March 29, 2018: British Journal of Radiology
https://www.readbyqxmd.com/read/29562686/profiling-prostate-cancer-therapeutic-resistance
#17
REVIEW
Cameron A Wade, Natasha Kyprianou
The major challenge in the treatment of patients with advanced lethal prostate cancer is therapeutic resistance to androgen-deprivation therapy (ADT) and chemotherapy. Overriding this resistance requires understanding of the driving mechanisms of the tumor microenvironment, not just the androgen receptor (AR)-signaling cascade, that facilitate therapeutic resistance in order to identify new drug targets. The tumor microenvironment enables key signaling pathways promoting cancer cell survival and invasion via resistance to anoikis...
March 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29556815/optimizing-the-treatment-of-metastatic-castration-resistant-prostate-cancer-a-latin-america-perspective
#18
REVIEW
Juan Pablo Sade, Carlos Alberto Vargas Báez, Martin Greco, Carlos Humberto Martínez, Miguel Ángel Álvarez Avitia, Carlos Palazzo, Narciso Hernández Toriz, Patricia Isabel Bernal Trujillo, Diogo Assed Bastos, Fabio Augusto Schutz, Santiago Bella, Lucas Nogueira, Neal D Shore
Prostate cancer is a significant burden and cause of mortality in Latin America. This article reviews the treatment options for patients with metastatic castration-resistant prostate cancer (mCRPC) and provides consensus recommendations to assist Latin American prostate cancer specialists with clinical decision making. A multidisciplinary expert panel from Latin America reviewed the available data and their individual experience to develop clinical consensus opinions for the use of life-prolonging agents in mCRPC, with consideration given to factors influencing patient selection and treatment monitoring...
March 19, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29556486/differences-in-clinical-outcome-between-docetaxel-and-abiraterone-acetate-as-the-first-line-treatment-in-chemo-na%C3%A3-ve-metastatic-castration-resistant-prostate-cancer-patients-with-or-without-the-ineligible-clinical-factors-of-the-cou-aa-302-study
#19
Darren M C Poon, Kuen Chan, Siu H Lee, Tim W Chan, Henry Sze, Eric K C Lee, Daisy Lam, Michelle F T Chan
Background: This study aimed to compare the efficacy of abiraterone acetate (AA) versus docetaxel (T) as first-line treatment in chemo-naïve metastatic castration-resistant prostate cancer (mCRPC) patients with or without the ineligible factors of the COU-AA-302 study (presence of visceral metastases, symptomatic disease, and/or Eastern Cooperative Oncology Group performance status ≥ 2). Materials and methods: The clinical records of chemo-naïve mCRPC patients who received AA in six public oncology centers or T in two of these centers between 2003 and 2014 were reviewed...
March 2018: Prostate International
https://www.readbyqxmd.com/read/29555412/the-resounding-effect-of-dna-repair-deficiency-in-prostate-cancer
#20
REVIEW
Heather H Cheng
An estimated one-fifth or more of metastatic castration-resistant prostate cancer (mCRPC) harbor defects in genes involved in DNA repair pathway (e.g., BRCA2, BRCA1, and others). Early evidence suggests these alterations may be predictive of therapeutic response to PARP inhibitors and platinum chemotherapy, thought to reflect principles of synthetic lethality and are currently being investigated in an increasing number of prospective clinical trials. Other studies have examined these alterations as prognostic biomarkers and in association with response to currently available treatments...
March 16, 2018: Urologic Oncology
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