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Abiraterone

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https://www.readbyqxmd.com/read/29774129/combined-abiraterone-acetate-plus-prednisone-salvage-prostate-bed-radiotherapy-and-lh-rh-agonists-carlha-gep12-in-biochemically-relapsing-prostate-cancer-patients-following-prostatectomy-a-phase-i-study-of-the-getug-gep
#1
Stéphane Supiot, Loic Campion, Pascal Pommier, Mélanie Dore, Clément Palpacuer, Séverine Racadot, Emmanuel Rio, Gérard A Milano, Céline Mahier-Ait Oukhatar, Christian Carrie
Background: To establish the maximum tolerated dose of abiraterone acetate plus prednisone (AA) combined with salvage radiotherapy (SRT) and goserelin in a phase 1 study in men with rising PSA following radical prostatectomy. Methods: AA was given during one month before SRT at 1000 mg PO once daily, then 750 mg (Dose Level 1, DL1) or 1000 mg (DL2) during 5 months combined with 6-months goserelin by injection on the first day of irradiation (scheme NEO) or one month before starting SRT (scheme CONCO)...
April 24, 2018: Oncotarget
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
#2
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/29752180/-177-lu-psma-617-radionuclide-treatment-in-patients-with-metastatic-castration-resistant-prostate-cancer-lupsma-trial-a-single-centre-single-arm-phase-2-study
#3
Michael S Hofman, John Violet, Rodney J Hicks, Justin Ferdinandus, Sue Ping Thang, Tim Akhurst, Amir Iravani, Grace Kong, Aravind Ravi Kumar, Declan G Murphy, Peter Eu, Price Jackson, Mark Scalzo, Scott G Williams, Shahneen Sandhu
BACKGROUND: Progressive metastatic castration-resistant prostate cancer is a highly lethal disorder and new effective therapeutic agents that improve patient outcomes are urgently needed. Lutetium-177 [177 Lu]-PSMA-617, a radiolabelled small molecule, binds with high affinity to prostate-specific membrane antigen (PSMA) enabling beta particle therapy targeted to metastatic castration-resistant prostate cancer. We aimed to investigate the safety, efficacy, and effect on quality of life of [177 Lu]-PSMA-617 in men with metastatic castration-resistant prostate cancer who progressed after standard treatments...
May 7, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29743517/identification-of-new-epha4-inhibitors-by-virtual-screening-of-fda-approved-drugs
#4
Shuo Gu, Wing-Yu Fu, Amy K Y Fu, Estella Pui Sze Tong, Fanny C F Ip, Xuhui Huang, Nancy Y Ip
The receptor tyrosine kinase, erythropoietin-producing hepatocellular A4 (EphA4), was recently identified as a molecular target for Alzheimer's disease (AD). We found that blockade of the interaction of the receptor and its ligands, ephrins, alleviates the disease phenotype in an AD transgenic mouse model, suggesting that targeting EphA4 is a potential approach for developing AD interventions. In this study, we identified five FDA-approved drugs-ergoloid, cyproheptadine, nilotinib, abiraterone, and retapamulin-as potential inhibitors of EphA4 by using an integrated approach combining virtual screening with biochemical and cellular assays...
May 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29742084/first-line-use-of-novel-hormonal-agents-in-prostate-cancer-a-critical-appraisal
#5
Derek Raghavan
Castration has been the hallmark of the treatment of advanced prostate cancer for nearly a century. Conventional surgical or medical castration for the management of metastatic prostate cancer has been associated with an initial response rate greater than 60% to 70%, depending on the criteria employed. The median duration of the initial response is usually less than 3 to 5 years, however, depending on the extent of disease. The failure of disease to respond to castration has been associated with an increase in the production of adrenal androgens and/or the evolution of upregulated or mutated androgen receptors...
April 2018: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/29741566/circulating-tumor-cell-increase-as-a-biomarker-of-disease-progression-in-metastatic-castration-resistant-prostate-cancer-patients-with-low-baseline-ctc-counts
#6
D Lorente, D Olmos, J Mateo, D Dolling, D Bianchini, G Seed, P Flohr, M Crespo, I Figueiredo, S Miranda, H I Scher, L W M M Terstappen, J S de Bono
Background: The development of treatment response and surrogate biomarkers for advanced prostate cancer care is an unmet clinical need. Patients with baseline circulating tumor cell counts (BLCTCs)<5/7.5 mL represent a good prognosis subgroup, but are non-evaluable for response assessment (decrease in CTCs). The aim of the study is to determine the value of any increase in CTCs (CTC Progression) as an indicator of progression in prostate cancer patients with low pre-treatment CTCs (<5)...
May 7, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29734647/recent-advances-in-prostate-cancer-treatment-and-drug-discovery
#7
REVIEW
Ekaterina Nevedomskaya, Simon J Baumgart, Bernard Haendler
Novel drugs, drug sequences and combinations have improved the outcome of prostate cancer in recent years. The latest approvals include abiraterone acetate, enzalutamide and apalutamide which target androgen receptor (AR) signaling, radium-223 dichloride for reduction of bone metastases, sipuleucel-T immunotherapy and taxane-based chemotherapy. Adding abiraterone acetate to androgen deprivation therapy (ADT) in order to achieve complete androgen blockade has proven highly beneficial for treatment of locally advanced prostate cancer and metastatic hormone-sensitive prostate cancer (mHSPC)...
May 4, 2018: International Journal of Molecular Sciences
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
#8
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/29725416/baseline-prostate-specific-antigen-levels-following-treatment-with-abiraterone-acetate-as-a-prognostic-factor-in-castration-resistant-prostate-cancer
#9
Tasuku Hiroshige, Yoshiro Eguchi, Osamu Yoshizumi, Katsuaki Chikui, Hisaji Kumagai, Yoshihiro Kawaguchi, Rei Onishi, Tokumasa Hayashi, Kouta Watanabe, Tomotaro Mitani, Koujiro Saito, Tsukasa Igawa
The aim of the present study was to investigate the prognostic factors associated with progression-free survival (PFS) and overall survival (OS) times in patients with castration-resistant prostate cancer (CRPC) who received treatment with abiraterone acetate (AA) in routine clinical settings. A total of 93 patients treated with AA between September 2014 and February 2017 were selected and their medical records were analyzed retrospectively. The median PFS time of docetaxel (DTX)-naïve patients was 171 days, and that of post-DTX patients was 56 days...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29722038/long-term-abiraterone-withdrawal-syndrome
#10
S Marin, R Querol, L Campins, M Miarons, A Font, P Lianes
WHAT IS KNOWN AND OBJECTIVE: Abiraterone acetate (AA) is an androgen receptor axis inhibitor, indicated together with prednisone, for metastatic castration-resistant prostate cancer. Withdrawal syndrome for classical antiandrogen treatments is well known, but not so known for AA. Abiraterone withdrawal syndrome (AWS) could be related to simultaneous prednisone discontinuation or to an androgenic effect of AA metabolites. CASE DESCRIPTION: A case is described of a patient with long-term AWS without prednisone discontinuation...
May 2, 2018: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/29710837/mechanism-of-the-dual-activities-of-human-cyp17a1-and-binding-to-anti-prostate-cancer-drug-abiraterone-revealed-by-a-novel-v366m-mutation-causing-17-20-lyase-deficiency
#11
Mónica Fernández-Cancio, Núria Camats, Christa E Flück, Adam Zalewski, Bernhard Dick, Brigitte M Frey, Raquel Monné, Núria Torán, Laura Audí, Amit V Pandey
The CYP17A1 gene regulates sex steroid biosynthesis in humans through 17&alpha;-hydroxylase/17,20 lyase activities and is a target of anti-prostate cancer drug abiraterone. In a 46, XY patient with female external genitalia, together with a loss of function mutation S441P, we identified a novel missense mutation V366M at the catalytic center of CYP17A1 which preferentially impaired 17,20 lyase activity. Kinetic experiments with bacterially expressed proteins revealed that V366M mutant enzyme can bind and metabolize pregnenolone to 17OH-pregnenolone, but 17OH-pregnenolone binding and conversion to dehydroepiandrosterone (DHEA) was impaired, explaining the patient&rsquo;s steroid profile...
April 29, 2018: Pharmaceuticals
https://www.readbyqxmd.com/read/29688882/withdrawn-disparity-in-public-funding-of-therapies-for-metastatic-castrate-resistant-prostate-cancer-across-canadian-provinces
#12
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/29682197/synthesis-and-anticancer-activity-of-the-derivatives-of-marine-compound-rhizochalin-in-castration-resistant-prostate-cancer
#13
Sergey A Dyshlovoy, Katharina Otte, Kseniya M Tabakmakher, Jessica Hauschild, Tatyana N Makarieva, Larisa K Shubina, Sergey N Fedorov, Carsten Bokemeyer, Valentin A Stonik, Gunhild von Amsberg
Development of resistance to standard therapies complicates treatment of advanced prostate cancer. Alternative splicing variants of the androgen receptor (AR), e.g. AR-V7 can mediate resistance to AR-targeting substances abiraterone and enzalutamide. Semi-synthetic marine natural compound rhizochalinin decreases the expression of AR-V7 in human castration-resistant prostate cancer cells and thus resensitizes cells to enzalutamide. In the current study, we modified the structure of rhizochalin in order to determine structure-activity relationships (SAR) and optimize anticancer properties...
March 30, 2018: Oncotarget
https://www.readbyqxmd.com/read/29682196/testosterone-metabolites-inhibit-proliferation-of-castration-and-therapy-resistant-prostate-cancer
#14
Felix Bremmer, Hubertus Jarry, Valerie Unterkircher, Silke Kaulfuss, Peter Burfeind, Heinz-Joachim Radzun, Philipp Ströbel, Paul Thelen
Novel treatments for castration-resistant prostate cancer (CRPC) such as abiraterone acetate (AA) or enzalutamide effectively target the androgen pathway to arrest aberrant signalling and cell proliferation. Testosterone is able to inhibit tumour cell growth in CRPC. Estrogen receptor-beta (ERβ) binds the testosterone-metabolites 3β-androstanediol and 3α-androstanediol in parallel to the canonical estradiol. In the prostate it is widely accepted that ERβ regulates estrogen signalling, mediating anti-proliferative effects...
March 30, 2018: Oncotarget
https://www.readbyqxmd.com/read/29680098/modeling-clinical-outcomes-in-prostate-cancer-application-and-validation-of-the-discrete-event-simulation-approach
#15
Feng Pan, Odette Reifsnider, Ying Zheng, Irina Proskorovsky, Tracy Li, Jianming He, Sonja V Sorensen
OBJECTIVES: Treatment landscape in prostate cancer has changed dramatically with the emergence of new medicines in the past few years. The traditional survival partition model (SPM) cannot accurately predict long-term clinical outcomes because it is limited by its ability to capture the key consequences associated with this changing treatment paradigm. The objective of this study was to introduce and validate a discrete-event simulation (DES) model for prostate cancer. METHODS: A DES model was developed to simulate overall survival (OS) and other clinical outcomes based on patient characteristics, treatment received, and disease progression history...
April 2018: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/29674118/germline-variant-in-hsd3b1-1245-a-c-and-response-to-abiraterone-acetate-plus-prednisone-in-men-with-new-onset-metastatic-castration-resistant-prostate-cancer
#16
Andrew W Hahn, David M Gill, Roberto H Nussenzveig, Austin Poole, Jim Farnham, Lisa Cannon-Albright, Neeraj Agarwal
BACKGROUND: The HSD3B1 gene encodes the enzyme 3β-hydroxysteroid dehydrogenase-1 (3βHSD1), which catalyzes adrenal androgen precursors into dihydrotestosterone, the most potent androgen. Recently, the HSD3B1 (1245C) variant was shown to predict shorter duration of response to androgen deprivation therapy with medical or surgical castration in the setting of castration-sensitive prostate cancer (CSPC). The HSD3B1 (1245C) variant also predicts longer duration of response to ketoconazole in men with castration-resistant prostate cancer (CRPC)...
March 27, 2018: Clinical Genitourinary Cancer
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
#17
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/29666838/a-brief-history-of-intracrine-androgen-metabolism-by-castration-recurrent-prostate-cancer
#18
REVIEW
James L Mohler
This mini-review describes the evolution of the concept of intracrine androgen metabolism by prostate cancer during androgen deprivation therapy. Persistence of androgen receptor protein in the face of castrate circulating levels of testosterone could not be explained fully by hypersensitization or mutation of the androgen receptor. The hypothesis that castration-recurrent prostate cancer produced its own testosterone was proven using radioimmunoassay and mass spectrometry methods adopted for use in prostate tissue...
2018: American Journal of Clinical and Experimental Urology
https://www.readbyqxmd.com/read/29644451/emerging-therapies-in-metastatic-prostate-cancer
#19
REVIEW
Daniel W Sonnenburg, Alicia K Morgans
PURPOSE OF REVIEW: In the last decade, there have been multiple landmark therapeutic advances for the treatment of metastatic prostate cancer, both in the castration-resistant and hormone-sensitive setting. In this review, we highlight recent progress and ongoing trials for metastatic prostate cancer, including advances in chemotherapy, androgen receptor-directed therapy, targeted therapies, and immunotherapy. RECENT FINDINGS: Several landmark studies for men with metastatic hormone-sensitive prostate cancer demonstrated improvement in overall survival with the addition of docetaxel chemotherapy or abiraterone acetate to standard androgen deprivation therapy...
April 11, 2018: Current Oncology Reports
https://www.readbyqxmd.com/read/29626324/apalutamide-first-global-approval
#20
Zaina T Al-Salama
Apalutamide (ErleadaTM ) is a next-generation oral androgen receptor (AR) inhibitor that is being developed by Janssen for the treatment of prostate cancer (PC). It binds directly to the ligand-binding domain of the AR and blocks the effects of androgens. In February 2018, apalutamide received its first global approval in the USA for the treatment of non-metastatic castration-resistant PC (nmCRPC). Apalutamide is undergoing phase III investigation in chemotherapy-naive patients with metastatic CRPC (in combination with abiraterone acetate plus prednisone), patients with high-risk localized or locally advanced PC receiving primary radiation therapy, and in patients with metastatic hormone-sensitive PC and biochemically-relapsed PC...
April 6, 2018: Drugs
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