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Abiraterone

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https://www.readbyqxmd.com/read/28529549/abiraterone-acetate-and-prednisone-in-chemotherapy-na%C3%A3-ve-prostate-cancer-patients-rationale-evidence-and-clinical-utility
#1
REVIEW
E David Crawford, Neal D Shore, Daniel P Petrylak, Celestia S Higano, Charles J Ryan
Abiraterone acetate 1000 mg/day, combined with prednisone 5 mg PO twice daily, is indicated for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Abiraterone acetate is the oral prodrug of abiraterone, a specific CYP17 inhibitor that blocks androgen biosynthesis within the adrenal glands, testes and tumor microenvironment. In a phase III trial of men with asymptomatic or minimally symptomatic, chemotherapy-naïve mCRPC, treatment with oral abiraterone acetate plus prednisone led to a statistically significant improvement in the co-primary endpoints of overall survival and radiographic progression-free survival when compared with placebo plus prednisone...
May 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28527407/mechanisms-of-resistance-to-systemic-therapy-in-metastatic-castration-resistant-prostate-cancer
#2
REVIEW
Giuseppe Galletti, Benjamin I Leach, Linda Lam, Scott T Tagawa
Patients with metastatic castration-resistant prostate cancer (mCPRC) now have an unprecedented number of approved treatment options, including chemotherapies (docetaxel, cabazitaxel), androgen receptor (AR)-targeted therapies (enzalutamide, abiraterone), a radioisotope (radium-223) and a cancer vaccine (sipuleucel-T). However, the optimal treatment sequencing pathway is unknown, and this problem is exacerbated by the issues of primary and acquired resistance. This review focuses on mechanisms of resistance to AR-targeted therapies and taxane-based chemotherapy...
May 8, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28490267/darolutamide-odm-201-for-the-treatment-of-prostate-cancer
#3
Neal D Shore
Androgen deprivation therapy (ADT) is a mainstay initial treatment for advanced hormone-sensitive prostate cancer (HSPC), but disease progression to castration-resistant prostate cancer (CRPC) invariably occurs when patients do not succumb to another disease or comorbidity. Recognition that the androgen receptor (AR) axis continues to drive disease progression has led to the development of several AR-directed approved agents, including abiraterone acetate and enzalutamide. An investigational agent, darolutamide (ODM-201, BAY-1841788), has completed early-phase clinical trials, and two global Phase III trials are currently accruing patients...
May 11, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28490047/development-and-validation-of-an-lc-ms-ms-method-for-the-simultaneous-quantification-of-abiraterone-enzalutamide-and-their-major-metabolites-in-human-plasma
#4
Merel van Nuland, M J X Hillebrand, H Rosing, J H M Schellens, J H Beijnen
BACKGROUND: Abiraterone acetate and enzalutamide are 2 novel drugs for the treatment of metastatic castration-resistant prostate cancer. The metabolism of these drugs is extensive. Major metabolites are N-desmethyl enzalutamide, enzalutamide carboxylic acid, abiraterone N-oxide sulfate, and abiraterone sulfate; of which N-desmethyl enzalutamide is reported to possess antiandrogen capacities. A liquid chromatography-tandem mass spectrometry method for simultaneous quantification of abiraterone, enzalutamide, and the main metabolites has been developed and validated to support therapeutic drug monitoring...
June 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28478884/abiraterone-acetate-for-treatment-of-metastatic-castration-resistant-prostate-cancer-in-chemotherapy-naive-patients-an-italian-analysis-of-patients-satisfaction
#5
Luca Cindolo, Clara Natoli, Cosimo De Nunzio, Michele De Tursi, Maurizio Valeriani, Silvana Giacinti, Salvatore Micali, Mino Rizzo, Giampaolo Bianchi, Eugenio Martorana, Marcello Scarcia, Giuseppe Mario Ludovico, Pierluigi Bove, Anastasia Laudisi, Oscar Selvaggio, Giuseppe Carrieri, Maida Bada, Pietro Castellan, Luca Topazio, Stefano Boccasile, Pasquale Ditonno, Paolo Chiodini, Luigi Schips
INTRODUCTION: Abiraterone acetate (AA) gives a significant improvement in survival for patients with metastatic castration-resistant prostate cancer (mCRPC) before and after chemotherapy and has a favorable effect on patients' health-related quality of life and pain. Only a few studies have investigated patient-reported outcomes (PROs) in AA treatment for mCRPC. The aim of this study was to investigate patients' satisfaction in men affected by mCRPC treated with AA. MATERIALS AND METHODS: This was a retrospective analysis of a database of consecutive chemonaive patients with progressive mCRPC...
April 11, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28473535/androgen-receptor-variant-ar-v9-is-co-expressed-with-ar-v7-in-prostate-cancer-metastases-and-predicts-abiraterone-resistance
#6
Manish Kohli, Yeung Ho, David W Hillman, Jamie L Van Etten, Christine Henzler, Rendong Yang, Jame M Sperger, Yingming Li, Elizabeth Tseng, Ting Hon, Tyson Clark, Winston Tan, Rachel E Carlson, Liguo Wang, Hugues Sicotte, Ho Thai, Rafael Jimenez, Haojie Huang, Peter T Vedell, Bruce W Eckloff, J Fernando Quevedo, Henry C Pitot, Brian Costello, Jin Jen, Eric D Wieben, Kevin A T Silverstein, Joshua M Lang, Liewei Wang, Scott M Dehm
Purpose: Androgen receptor (AR) variant AR-V7 is a ligand-independent transcription factor that promotes prostate cancer resistance to AR-targeted therapies.  Accordingly, efforts are underway to develop strategies for monitoring and inhibiting AR-V7 in castration-resistant prostate cancer (CRPC).  The purpose of this study was to understand whether other AR variants may be co-expressed with AR-V7 and promote resistance to AR-targeted therapies.<br /><br /> Experimental Design:  We utilized complementary short- and long-read sequencing of intact AR mRNA isoforms to characterize AR expression in CRPC models...
May 4, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28472366/androgen-receptor-gene-status-in-plasma-dna-associates-with-worse-outcome-on-enzalutamide-or-abiraterone-for-castration-resistant-prostate-cancer-a-multi-institution-correlative-biomarker-study
#7
V Conteduca, D Wetterskog, M T A Sharabiani, E Grande, M P Fernandez-Perez, A Jayaram, S Salvi, D Castellano, A Romanel, C Lolli, V Casadio, G Gurioli, D Amadori, A Font, S Vazquez-Estevez, A González Del Alba, B Mellado, O Fernandez-Calvo, M J Méndez-Vidal, M A Climent, I Duran, E Gallardo, A Rodriguez, C Santander, M I Sáez, J Puente, D Gasi Tandefelt, A Wingate, D Dearnaley, F Demichelis, U De Giorgi, E Gonzalez-Billalabeitia, G Attard
Background: There is an urgent need to identify biomarkers to guide personalized therapy in castration-resistant prostate cancer (CRPC). We aimed to clinically qualify androgen receptor (AR) gene status measurement in plasma DNA using multiplex droplet digital PCR (ddPCR) in pre- and post-chemotherapy CRPC. Methods: We optimized ddPCR assays for AR copy number and mutations and retrospectively analyzed plasma DNA from patients recruited to one of the three biomarker protocols with prospectively collected clinical data...
May 3, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28463227/androgen-receptor-antagonism-drives-cytochrome-p450-17a1-inhibitor-efficacy-in-prostate-cancer
#8
John D Norris, Stephanie J Ellison, Jennifer G Baker, David B Stagg, Suzanne E Wardell, Sunghee Park, Holly M Alley, Robert M Baldi, Alexander Yllanes, Kaitlyn J Andreano, James P Stice, Scott A Lawrence, Joel R Eisner, Douglas K Price, William R Moore, William D Figg, Donald P McDonnell
The clinical utility of inhibiting cytochrome P450 17A1 (CYP17), a cytochrome p450 enzyme that is required for the production of androgens, has been exemplified by the approval of abiraterone for the treatment of castration-resistant prostate cancer (CRPC). Recently, however, it has been reported that CYP17 inhibitors can interact directly with the androgen receptor (AR). A phase I study recently reported that seviteronel, a CYP17 lyase-selective inhibitor, demonstrated a sustained reduction in prostate-specific antigen in a patient with CRPC, and another study showed seviteronel's direct effects on AR function...
May 2, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28455853/exploring-the-optimal-sequence-of-abiraterone-and-enzalutamide-in-patients-with-chemotherapy-na%C3%A3-ve-castration-resistant-prostate-cancer-the-kyoto-baltimore-collaboration
#9
Naoki Terada, Benjamin L Maughan, Shusuke Akamatsu, Takashi Kobayashi, Toshinari Yamasaki, Takahiro Inoue, Tomomi Kamba, Osamu Ogawa, Emmanuel S Antonarakis
OBJECTIVES: To evaluate and compare the efficacy of sequential treatment with abiraterone followed by enzalutamide or vice versa for castration-resistant prostate cancer. METHODS: We retrospectively evaluated data on 198 consecutive chemotherapy-naïve patients who had received both abiraterone and enzalutamide for castration-resistant prostate cancer at Kyoto University Hospital (including satellite hospitals) and at Johns Hopkins Cancer Center. Prostate-specific antigen progression-free survival and overall survival in patients treated with sequential abiraterone-to-enzalutamide versus enzalutamide-to-abiraterone without intervening therapies were compared...
April 28, 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/28452846/abiraterone-associated-fulminant-liver-failure
#10
Prabhsimranjot Singh, Ankur Sinha, Tsering G Lama Tamang, Abhinav B Chandra, Yiwu Jim Huang
No abstract text is available yet for this article.
April 25, 2017: American Journal of Therapeutics
https://www.readbyqxmd.com/read/28449621/emerging-role-of-radium-223-in-the-growing-therapeutic-armamentarium-of-metastatic-castration-resistant-prostate-cancer
#11
Maria Picciotto, Tindara Franchina, Alessandro Russo, Giuseppina Rosaria Rita Ricciardi, Giusy Provazza, Serena Sava, Sergio Baldari, Orazio Caffo, Vincenzo Adamo
During the last few years, the therapeutic armamentarium of castration resistant prostate cancer (mCRPC) has been enriched with the introduction of new effective therapies with proved survival benefit and quality of life gain, including cabazitaxel, abiraterone, enzalutamide, and Radium-223. Areas covered: Bone metastases represent a substantial cause of morbidity in mCRPC with a high rate of related skeletal events (SREs). In case of multifocal pain due to diffuse osteoblastic metastases, treatment with bone-targeting radiopharmaceutical agents can provide palliation from pain...
May 8, 2017: Expert Opinion on Pharmacotherapy
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
#12
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
#13
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...
June 2017: Prostate
https://www.readbyqxmd.com/read/28427506/recent-advances-in-genitourinary-tumors-a-review-focused-on-biology-and-systemic-treatment
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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