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Abiraterone

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https://www.readbyqxmd.com/read/28441112/second-line-hormonal-therapy-for-men-with-chemotherapy-na%C3%A3-ve-castration-resistant-prostate-cancer-american-society-of-clinical-oncology-provisional-clinical-opinion
#1
Katherine S Virgo, Ethan Basch, D Andrew Loblaw, Tom Oliver, R Bryan Rumble, Michael A Carducci, Luke Nordquist, Mary-Ellen Taplin, Eric Winquist, Eric A Singer
Purpose ASCO provisional clinical opinions (PCOs) offer direction to the ASCO membership after publication or presentation of potential practice-changing data. This PCO addresses second-line hormonal therapy for chemotherapy-naïve men with castration-resistant prostate cancer (CRPC) who range from being asymptomatic with only biochemical evidence of CRPC to having documented metastases but minimal symptoms. Clinical Context The treatment goal for CRPC is palliation. Despite resistance to initial androgen deprivation therapy, most men respond to second-line hormonal therapies...
April 25, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28429372/long-term-clinical-impact-of-psa-surge-in-castration-resistant-prostate-cancer-patients-treated-with-abiraterone
#2
Vincenza Conteduca, Orazio Caffo, Cristian Lolli, Michele Aieta, Emanuela Scarpi, Emanuela Bianchi, Francesca Maines, Giuseppe Schepisi, Samanta Salvi, Francesco Massari, Francesco Carrozza, Antonello Veccia, Vincenzo E Chiuri, Enrico Campadelli, Gaetano Facchini, Ugo De Giorgi
BACKGROUND: Early changes in PSA have been evaluated in association to treatment outcome. The aim of this study was to assess PSA surge phenomenon in castration-resistant prostate cancer (CRPC) patients treated with abiraterone and to correlate those variations with long-term treatment outcome. PATIENTS AND METHODS: We retrospectively evaluated 330 CRPC patients in 11 Italian hospitals, monitoring PSA levels at baseline and every 4 weeks. Other clinical, biochemical and molecular parameters were determined at baseline...
April 20, 2017: Prostate
https://www.readbyqxmd.com/read/28427506/recent-advances-in-genitourinary-tumors-a-review-focused-on-biology-and-systemic-treatment
#3
REVIEW
Aránzazu González Del Alba, José Ángel Arranz, Javier Puente, María José Méndez-Vidal, Enrique Gallardo, Enrique Grande, Begoña Pérez-Valderrama, Enrique González-Billalabeitia, Martín Lázaro-Quintela, Álvaro Pinto, Nuria Lainez, Josep M Piulats, Emilio Esteban, José Pablo Maroto Rey, Jorge A García, Cristina Suárez
Updated information published up to 2016 regarding major advances in renal cancer, bladder cancer, and prostate cancer is here presented. Based on an ever better understanding of the genetic and molecular alterations that govern the initial pathogenic mechanisms of tumor oncogenesis, an improvement in the characterization and treatment of urologic tumors has been achieved in the past year. According to the Cancer Genome Atlas (ATLAS) project, alterations in the MET pathway are characteristics of type 1 papillary renal cell carcinomas, and activation of NRF2-ARE pathway is associated with the biologically distinct type 2...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28426121/phase-ii-study-of-cabazitaxel-with-or-without-abiraterone-acetate-and-prednisone-in-patients-with-metastatic-castrate-resistant-prostate-cancer-after-prior-docetaxel-and-abiraterone-acetate
#4
E R Kessler, D Gao, T W Flaig, K Breaker, M Wold, M Wacker, E T Lam
No abstract text is available yet for this article.
March 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28426107/controversies-and-consensus-in-the-innovation-access-for-cancer-therapy-in-the-european-countries-on-the-subject-of-metastatic-prostate-cancer
#5
S Oudard, F Courbon
Innovative cancer therapies and advances in drug development have created new hopes for patients and health providers. The purpose of this article was to evaluate the discrepancies in the assessment of the magnitude of benefit of four new drugs (abiraterone acetate, enzalutamide, cabazitaxel, radium-223 dichloride) for the treatment of metastatic castration-resistant prostate cancer (mCRPC). The comparison was done among three European countries (UK, Germany and France) and Canada, according to the statement of each country and to the European Society of Medical Oncology (ESMO) Magnitude of Clinical Benefit Scale...
February 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28425029/comparison-of-a-novel-formulation-of-abiraterone-acetate-vs-the-originator-formulation-in-healthy-male-subjects-two-randomized-open-label-crossover-studies
#6
Ronald Goldwater, Azra Hussaini, Bill Bosch, Paul Nemeth
BACKGROUND AND OBJECTIVE: Abiraterone acetate is approved for the treatment of metastatic castration-resistant prostate cancer. The originator abiraterone acetate (OAA) formulation is poorly absorbed and exhibits large pharmacokinetic variability in abiraterone exposure. Abiraterone acetate fine particle (AAFP) is a proprietary formulation (using SoluMatrix Fine Particle Technology™) designed to increase the oral bioavailability of abiraterone acetate. Here, we report on two phase I studies in healthy male subjects aged 18-50 years...
April 19, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28414609/association-between-androgen-receptor-splice-variants-and-prostate-cancer-resistance-to-abiraterone-and-enzalutamide
#7
Glenn J Bubley, Steven P Balk
No abstract text is available yet for this article.
April 17, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28411207/transdifferentiation-as-a-mechanism-of-treatment-resistance-in-a-mouse-model-of-castration-resistant-prostate-cancer
#8
Min Zou, Roxanne Toivanen, Antonina Mitrofanova, Nicolas Floc'h, Sheida Hayati, Yanping Sun, Clementine Le Magnen, Daniel Chester, Elahe A Mostaghel, Andrea Califano, Mark A Rubin, Michael M Shen, Cory Abate-Shen
Current treatments for castration-resistant prostate cancer (CPRC) that target androgen receptor (AR) signaling improve patient survival, yet ultimately fail. Here we provide novel insights into treatment response for the anti-androgen abiraterone by analyses of a genetically-engineered mouse model (GEMM) with combined inactivation of Trp53 and Pten, which are frequently co-mutated in human CRPC. These NPp53 mice fail to respond to abiraterone, and display accelerated progression to tumors resembling treatment-related CRPC with neuroendocrine differentiation (CRPC-NE) in humans...
April 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28401143/impact-of-abiraterone-acetate-with-and-without-prior-docetaxel-chemotherapy-on-the-survival-of-patients-with-metastatic-castration-resistant-prostate-cancer-a-population-based-study
#9
Joice Rocha, Armen G Aprikian, Marie Vanhuyse, Fabio L Cury, Jason Hu, Noémie Prévost, Alice Dragomir
BACKGROUND: Abiraterone acetate was introduced in Quebec in 2012 for the treatment of metastatic castration-resistant prostate cancer (mCRPC) in patients who had received chemotherapy with docetaxel. This study describes abiraterone use in the early postapproval period and its clinical effectiveness in Quebec, for both patients who had received docetaxel chemotherapy and those who could not receive docetaxel therapy owing to medical reasons. METHODS: A retrospective cohort study was conducted using Quebec public health care administrative databases...
January 2017: CMAJ Open
https://www.readbyqxmd.com/read/28395931/impact-of-abiraterone-acetate-and-enzalutamide-on-symptom-burden-of-patients-with-chemotherapy-naive-metastatic-castration-resistant-prostate-cancer
#10
S Salem, M Komisarenko, N Timilshina, L Martin, R Grewal, S Alibhai, A Finelli
AIMS: Treatments and disease burden of metastatic castration-resistant prostate cancer (mCRPC) considerably affect a patient's quality of life. However, patient-reported symptom burden data are still largely insufficient. This study sought to compare the self-reported symptom burden of men with chemotherapy-naive (CN) mCRPC treated with abiraterone acetate (AA) or enzalutamide (EZ) in routine clinical practice. MATERIALS AND METHODS: Between 2011 and 2015, 189 CN-mCRPC patients who had received AA (n = 76) or EZ (n = 113) at the Princess Margaret Cancer Centre were included...
April 8, 2017: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/28390646/first-line-management-of-metastatic-castrate-resistant-prostate-cancer-patients-audit-of-real-life-practices
#11
Anthony Turpin, David Pasquier, Christophe Massard, Jean-François Berdah, Stéphane Culine, Nicolas Penel
BACKGROUND: No reliable guidelines are available for choosing the best option between docetaxel and new hormonal therapies (NHTs) (i.e., abiraterone and enzalutamide) in first-line therapy for metastatic castration-resistant prostate cancer (mCRPC) patients. We performed an audit of real-life practices. METHODS: We built an online questionnaire and distributed it with the help of French oncology networks. This questionnaire was sent to 481 physicians who treat patients with mCRPC...
April 5, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/28389510/association-of-tissue-abiraterone-levels-and-slco-genotype-with-intraprostatic-steroids-and-pathologic-response-in-men-with-high-risk-localized-prostate-cancer
#12
Elahe A Mostaghel, Eunpi Cho, Ailin Zhang, Mohammad Alyamani, Arja Kaipainen, Sean Green, Brett Marck, Nima Sharifi, Jonathan L Wright, Roman Gulati, Lawrence D True, Massimo Loda, Alvin M Matsumoto, Daniel Tamae, Trevor N Penning, Steven P Balk, Philip W Kantoff, Peter S Nelson, Mary-Ellen Taplin, Bruce Montgomery
Germline variation in solute carrier organic anion (SLCO) genes influences cellular steroid uptake and is associated with prostate cancer (PCa) outcomes. We hypothesized that, due to its steroidal structure, the CYP17A inhibitor abiraterone may undergo SLCO-mediated transport and that SLCO gene variation may influence intracellular abiraterone levels and outcomes.<br /><br />Experimental Design: Steroid and abiraterone levels were measured by mass spectrometry in serum and tissue from 58 men with localized PCa in a clinical trial of LHRH agonist plus abiraterone acetate plus prednisone for 24 weeks prior to prostatectomy...
April 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28384066/clinical-significance-of-androgen-receptor-splice-variant-7-mrna-detection-in-circulating-tumor-cells-of-men-with-metastatic-castration-resistant-prostate-cancer-treated-with-first-and-second-line-abiraterone-and-enzalutamide
#13
Emmanuel S Antonarakis, Changxue Lu, Brandon Luber, Hao Wang, Yan Chen, Yezi Zhu, John L Silberstein, Maritza N Taylor, Benjamin L Maughan, Samuel R Denmeade, Kenneth J Pienta, Channing J Paller, Michael A Carducci, Mario A Eisenberger, Jun Luo
Purpose We reported previously that the detection of androgen receptor splice variant-7 (AR-V7) mRNA in circulating tumor cells (CTCs) correlated with poor outcomes from the use of abiraterone and enzalutamide in patients with castration-resistant prostate cancer (CRPC). Here, we expanded our cohort size to better characterize the prognostic significance of AR-V7 in this setting. Methods We prospectively enrolled 202 patients with CRPC starting abiraterone or enzalutamide and investigated the prognostic value of CTC detection (+ v -) and AR-V7 detection (+ v -) using a CTC-based AR-V7 mRNA assay...
April 6, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28373265/structural-and-functional-evaluation-of-clinically-relevant-inhibitors-of-steroidogenic-cytochrome-p450-17a1-cyp17a1
#14
Elyse M Petrunak, Steven A Rogers, Jeffrey Aube, Emily E Scott
Human steroidogenic cytochrome P450 17A1 (CYP17A1) is a bifunctional enzyme that performs both hydroxylation and lyase reactions, with the latter required to generate androgens that fuel prostate cancer proliferation. The steroid abiraterone, the active form of the only FDA- approved CYP17A1 inhibitor, binds the catalytic heme iron, nonselectively impeding both reactions and ultimately causing undesirable corticosteroid imbalance. Some non-steroidal inhibitors reportedly inhibit the lyase reaction more than the preceding hydroxylase reaction, which would be clinically advantageous, but the mechanism is not understood...
April 3, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28370882/safety-and-efficacy-of-2-weekly-cabazitaxel-in-metastatic-castration-resistant-prostate-cancer
#15
A Clément-Zhao, M Auvray, H Aboudagga, F Blanc-Durand, A Angelergues, Y A Vano, F Mercier, N El Awadly, B Verret, C Thibault, S Oudard
OBJECTIVES: To evaluate the safety and efficacy of a 2-weekly cabazitaxel schedule in metastatic castration-resistant prostate cancer (mCRPC) patients. MATERIALS AND METHODS: From October 2013 to February 2016, 43 mCRPC patients were treated with cabazitaxel (16 mg/m(2) on days 1 and 15 of a 4-week cycle) with G-CSF support. The safety profile and efficacy (prostate-specific antigen [PSA] response; biological, clinical or radiological progression-free survival [PFS] and overall survival [OS]) were analyzed...
March 28, 2017: BJU International
https://www.readbyqxmd.com/read/28370076/analytical-challenges-in-quantifying-abiraterone-with-lc-ms-ms-in-human-plasma
#16
Guillemette E Benoist, Eric van der Meulen, Floor J E Lubberman, Winald R Gerritsen, Tineke J Smilde, Jack A Schalken, Jan H Beumer, David M Burger, Nielka P van Erp
A method was developed and validated to quantify abiraterone in human plasma. During assay development several analytical challenges were encountered: limited stability in patient samples, adsorption to glass, co-elution with metabolites, and carry-over issues. Limited stability (2 h) was found for abiraterone in fresh plasma as well as whole blood at ambient temperature. When kept at 2-8 °C, abiraterone in plasma was stable for 24 h and in whole blood for 8 h. Adsorption of abiraterone to glass materials was addressed by using polypropylene throughout the method...
April 3, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28368512/androgen-receptor-rearrangement-and-splicing-variants-in-resistance-to-endocrine-therapies-in-prostate-cancer
#17
Yeung Ho, Scott M Dehm
The past few years have witnessed a significant improvement in the survival of patients with castration-resistant prostate cancer (CRPC) due to the development of second generation androgen deprivation therapies (ADT) such as abiraterone and second generation antagonists such as enzalutamide. However, CRPC patients rapidly develop resistance to these drugs, in many cases due to re-activation of the therapeutic target, the androgen receptor (AR) transcription factor. Several mechanisms responsible for AR transcriptional re-activation have been demonstrated, including mutation, amplification, or rearrangement of the AR gene, transcriptional compensation by alternative steroid receptors, and mutation or copy number alteration of genes encoding AR co-regulators...
March 27, 2017: Endocrinology
https://www.readbyqxmd.com/read/28367230/efficacy-of-cabazitaxel-treatment-in-metastatic-castration-resistant-prostate-cancer-in-second-and-later-lines-an-experience-from-two-german-centers
#18
Stefanie Zschäbitz, Sonia Vallet, Boris Hadaschik, Daniel Debatin, Stefan Fuxius, Andreas Karcher, Sascha Pahernik, Cathleen Spath, Stefan Duensing, Dirk Jäger, Markus Hohenfellner, Carsten Grüllich
Purpose: Several new treatment options for patients with metastatic castration resistant prostate cancer (mCRPC) have been approved within the last years - among them cabazitaxel (CAB), abiraterone acetate, enzalutamide, and radium-223. The aim of this study was to assess factors predictive for efficacy of CAB. Methods: We analyzed all patients with mCRPC treated with CAB at our institutions between 2011 and 2016. Data were retrieved retrospectively from the electronical patient chart. Results: 69 patients received CAB (26...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28364014/radium-223-inhibits-osseous-prostate-cancer-growth-by-dual-targeting-of-cancer-cells-and-bone-microenvironment-in-mouse-models
#19
Mari I Suominen, Katja M Fagerlund, Jukka P Rissanen, Yvonne M Konkol, Jukka P Morko, ZhiQi Peng, Esa J Alhoniemi, Salla K Laine, Eva Corey, Dominik Mumberg, Karl Ziegelbauer, Sanna-Maria Käkönen, Jussi Halleen, Robert L Vessella, Arne Scholz
Radium-223 dichloride (radium-223, Xofigo®), a targeted alpha therapy, is currently used for the treatment of patients with castration-resistant prostate cancer (CRPC) with bone metastases. This study examines the mode-of-action and antitumor efficacy of radium-223 in two prostate cancer xenograft models. <br /><br />Experimental Design: Mice bearing intratibial LNCaP or LuCaP 58 tumors were randomized to groups (n = 12-17) based on lesion grade and/or serum PSA level and administered with radium-223 (300 kBq/kg) or vehicle, twice at 4-week intervals...
March 31, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28361167/potential-drug-drug-interactions-with-abiraterone-in-metastatic-castration-resistant-prostate-cancer-patients-a-prevalence-study-in-france
#20
Clément Bonnet, Pascaline Boudou-Rouquette, Esther Azoulay-Rutman, Olivier Huillard, Jean-Louis Golmard, Edith Carton, Gaëlle Noé, Michel Vidal, Galdric Orvoen, Anne Chah Wakilian, Clémentine Villeminey, Benoit Blanchet, Jérôme Alexandre, François Goldwasser, Audrey Thomas-Schoemann
PURPOSE: Abiraterone acetate combined with prednisone improves survival in metastatic castration-resistant prostate cancer (mCRPC) patients. This oral anticancer agent may result in drug-drug interactions (DDI). We aimed to evaluate the prevalence of DDI with abiraterone and the possible determinants for the occurrence of these DDI. METHODS: We performed a single centre retrospective review from electronic medical records of mCRPC patients treated with abiraterone from 2011 to 2015...
March 30, 2017: Cancer Chemotherapy and Pharmacology
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