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Treatment resistant mCRPC

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https://www.readbyqxmd.com/read/28213364/safety-and-antitumor-activity-of-apalutamide-arn-509-in-metastatic-castration-resistant-prostate-cancer-with-and-without-prior-abiraterone-acetate-and-prednisone
#1
Dana E Rathkopf, Emmanuel S Antonarakis, Neal D Shore, Ronald F Tutrone, Joshi J Alumkal, Charles J Ryan, Mansoor Saleh, Ralph J Hauke, Rajesh Bandekar, Edna Chow Maneval, Carla J de Boer, Margaret K Yu, Howard I Scher
PURPOSE: To evaluate the efficacy of apalutamide before or after treatment with abiraterone acetate and prednisone (AAP) in patients with progressive metastatic castration-resistant prostate cancer (mCRPC). EXPERIMENTAL DESIGN: Two cohorts were studied: AAP-naïve and post-AAP patients who had received ≥6 months of AAP. Patients had progressive mCRPC per rising prostate-specific antigen (PSA) and/or imaging, without prior chemotherapy exposure. All received apalutamide 240 mg/day...
February 17, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28212536/targeting-the-stress-oncoprotein-ledgf-p75-to-sensitize-chemoresistant-prostate-cancer-cells-to-taxanes
#2
Leslimar Ríos-Colón, Christina K Cajigas-Du Ross, Anamika Basu, Catherine Elix, Ivana Alicea-Polanco, Tino W Sanchez, Vinodh Radhakrishnan, Chien-Shing Chen, Carlos A Casiano
Prostate cancer (PCa) is associated with chronic prostate inflammation resulting in activation of stress and pro-survival pathways that contribute to disease progression and chemoresistance. The stress oncoprotein lens epithelium-derived growth factor p75 (LEDGF/p75), also known as DFS70 autoantigen, promotes cellular survival against environmental stressors, including oxidative stress, radiation, and cytotoxic drugs. Furthermore, LEDGF/p75 overexpression in PCa and other cancers has been associated with features of tumor aggressiveness, including resistance to cell death and chemotherapy...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28188090/independent-association-between-time-to-prostate-specific-antigen-psa-nadir-and-psa-progression-free-survival-in-patients-with-docetaxel-na%C3%A3-ve-metastatic-castration-resistant-prostate-cancer-receiving-abiraterone-acetate-but-not-enzalutamide
#3
Hideaki Miyake, Takuto Hara, Keita Tamura, Takayuki Sugiyama, Hiroshi Furuse, Seiichiro Ozono, Masato Fujisawa
PURPOSE: The objective of this study was to compare the prognostic effect of time to prostate-specific antigen (PSA) nadir (TTPN) after treatment with abiraterone acetate (AA) and enzalutamide (Enz) in patients with docetaxel-naïve, metastatic castration-resistant prostate cancer (mCRPC). METHODS: This study included a total of 297 consecutive patients with mCRPC, of whom 125 and 172 received AA and Enz, respectively, without previous treatment with docetaxel and subsequently achieved any degree of PSA reduction after the administration of either agent...
February 7, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28185462/-options-of-chemotherapy-in-the-treatment-of-prostate-cancer
#4
I Richter, J Dvořák, J Bartoš
BACKGROUND: Prostate cancer is one of the most common malignancies in men. Chemotherapy has an important role in the management of prostate cancer, especially for the treatment of castrate resistant prostate cancer (mCRPC). According to recently published studies, chemotherapy can also be used to treat advanced hormone sensitive disease. AIM: The aim of this report is to review the currently available options for chemotherapy of prostate cancer. RESULTS: Docetaxel is a chemotherapeutic agent used for standard treatment of mCRPC as 1st line therapy...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/28171710/clinical-outcomes-and-survival-surrogacy-studies-of-prostate-specific-antigen-declines-following-enzalutamide-in-men-with-metastatic-castration-resistant-prostate-cancer-previously-treated-with-docetaxel
#5
Andrew J Armstrong, Fred Saad, De Phung, Carl Dmuchowski, Neal D Shore, Karim Fizazi, Mohammad Hirmand, David Forer, Howard I Scher, Johann De Bono
BACKGROUND: In the AFFIRM trial, enzalutamide significantly increased overall survival (OS) for men with metastatic castration-resistant prostate cancer (mCRPC) after chemotherapy versus placebo and significantly decreased prostate-specific antigen (PSA) levels. The goal of this post hoc analysis was to associate levels of PSA decline from baseline after enzalutamide with clinical outcomes in the postchemotherapy mCRPC setting. METHODS: Men in the AFFIRM trial (n = 1199) were grouped by maximal PSA decline in the first 90 days of treatment...
February 7, 2017: Cancer
https://www.readbyqxmd.com/read/28161841/prognostic-factors-of-first-line-docetaxel-treatment-in-castration-resistant-prostate-cancer-roles-of-neutrophil-to-lymphocyte-ratio-in-patients-from-northwestern-china
#6
Xin-Qi Pei, Da-Lin He, Ge Tian, Wei Lv, Yu-Mei Jiang, Da-Peng Wu, Jin-Hai Fan, Kai-Jie Wu
OBJECTIVE: To evaluate the potential role of neutrophil-to-lymphocyte ratio (NLR) with therapeutic response in patients who were treated with docetaxel for mCRPC. MATERIALS AND METHODS: We retrospectively analyzed the clinical data from 111 consecutive patients who were treated with docetaxel for mCRPC from 2009 to 2016 in a single center from Northwestern China. Pretreatment baseline and follow-up data including age, PSA response, Gleason score, and cycle number were reviewed, and multivariable Cox regression models and Kaplan-Meier analysis were used to predict overall survival (OS) and progression-free survival (PFS)...
February 4, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28161323/a-multicenter-phase-i-study-of-cabazitaxel-mitoxantrone-and-prednisone-for-chemotherapy-na%C3%A3-ve-patients-with-metastatic-castration-resistant-prostate-cancer-a-department-of-defense-prostate-cancer-clinical-trials-consortium-study
#7
Rahul Aggarwal, Alan Bryce, Charles J Ryan, Andrea Harzstark, Christina Derleth, Won Kim, Terence Friedlander, Amy M Lin, Tammy Rodvelt-Bagchi, Mallika Dhawan, Li Zhang, Mina Lee, Eric Siebeneck, Jeffrey Hough, Eric J Small
BACKGROUND: Cabazitaxel plus prednisone has significant activity in patients with chemotherapy-naïve and pretreated metastatic castration-resistant prostate cancer (mCRPC). Mitoxantrone has antitumor activity in mCRPC and nonoverlapping mechanism of action and toxicity profile. OBJECTIVE: To establish the maximally tolerated dose of the combination of cabazitaxel, mitoxantrone, and prednisone. METHODS AND MATERIALS: Patients with chemotherapy-naïve mCRPC were prospectively enrolled in a multicenter phase 1 trial...
February 1, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28151974/assessment-of-a-prognostic-model-psa-metrics-and-toxicities-in-metastatic-castrate-resistant-prostate-cancer-using-data-from-project-data-sphere-pds
#8
Bethany Pitcher, Leila Khoja, Robert J Hamilton, Kald Abdallah, Melania Pintilie, Anthony M Joshua
BACKGROUND: Prognostic models in metastatic castrate resistant prostate cancer (mCRPC) may have clinical utility. Using data from PDS, we aimed to 1) validate a contemporary prognostic model (Templeton et al., 2014) 2) evaluate prognostic impact of concomitant medications and PSA decrease 3) evaluate factors associated with docetaxel toxicity. METHODS: We accessed data on 2,449 mCRPC patients in PDS. The existing model was validated with a continuous risk score, time-dependent receiver operating characteristic (ROC) curves, and corresponding time-dependent Area under the Curve (tAUC)...
2017: PloS One
https://www.readbyqxmd.com/read/28144789/procaid-a-phase-i-clinical-trial-to-combine-the-akt-inhibitor-azd5363-with-docetaxel-and-prednisolone-chemotherapy-for-metastatic-castration-resistant-prostate-cancer
#9
Simon J Crabb, Alison J Birtle, Karen Martin, Nichola Downs, Ian Ratcliffe, Tom Maishman, Mary Ellis, Gareth Griffiths, Stuart Thompson, Lidia Ksiazek, Vincent Khoo, Robert J Jones
Background Docetaxel and prednisolone chemotherapy (DP) extends survival in metastatic castration resistant prostate cancer (mCRPC). However, emergent clinical resistance is almost inevitable. AKT pathway activation is highly prevalent in mCRPC contributing to disease progression and DP resistance. AZD5363 is a potent oral pan-AKT inhibitor with pre-clinical data indicating activity in mCRPC and synergy with docetaxel. Methods This phase I trial was to determine an AZD5363 recommended phase II dose (RP2D) for combination with DP...
February 1, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28131750/efficacy-of-eplerenone-in-the-management-of-mineralocorticoid-excess-in-men-with-metastatic-castration-resistant-prostate-cancer-treated-with-abiraterone-without-prednisone
#10
David Gill, David Gaston, Erin Bailey, Andrew Hahn, Sumati Gupta, Julia Batten, Anitha Alex, Kenneth Boucher, David Stenehjem, Neeraj Agarwal
BACKGROUND: Abiraterone acetate has been approved for metastatic castration-resistant prostate cancer (mCRPC). Coadministration with prednisone has been recommended to prevent the toxicity from secondary mineralocorticoid excess, such as hypertension, hypokalemia, and edema. However, the use of prednisone is often not desired by patients because of the potential for detrimental effects of long-term therapy with corticosteroids, especially in those with comorbidities such as diabetes or who have received previous immunotherapeutic agents...
January 5, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28126272/prostate-specific-antigen-response-in-black-and-white-patients-treated-with-abiraterone-acetate-for-metastatic-castrate-resistant-prostate-cancer
#11
Sundhar Ramalingam, Michael S Humeniuk, Rachel Hu, Julia Rasmussen, Patrick Healy, Yuan Wu, Michael R Harrison, Andrew J Armstrong, Daniel J George, Tian Zhang
PURPOSE: Evidence suggests differences in androgen receptor AR signaling between black (B) and white (W) patients with prostate cancer, but pivotal trials of abiraterone acetate (AA) for patients with metastatic castration-resistant prostate cancer (mCRPC) enrolled few black patients, a population with a higher mortality from prostate cancer. Our primary objective was to determine differences in response to AA between B and W patients. METHODS: We performed a retrospective case-control study of B vs...
January 23, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28125362/duration-of-treatment-in-prostate-cancer-patients-treated-with-abiraterone-acetate-or-enzalutamide
#12
Dominic Pilon, Ajay S Behl, Lorie A Ellis, Bruno Emond, Patrick Lefebvre, Nancy A Dawson
BACKGROUND: Abiraterone acetate (AA) and enzalutamide (ENZ) are oral therapies offering survival benefit to metastatic castration-resistant prostate cancer (mCRPC) patients. Despite the availability of multiple treatment options for mCRPC, there is a lack of information on the effect that being initiated on AA or ENZ has on the combined prostate cancer treatment duration. OBJECTIVE: To compare the combined duration of prostate cancer treatments of patients initiated on AA with that of patients initiated on ENZ...
February 2017: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/28123517/role-of-free-testosterone-levels-in-patients-with-metastatic-castration-resistant-prostate-cancer-receiving-second-line-therapy
#13
Christoph A von Klot, Markus A Kuczyk, Alena Boeker, Christoph Reuter, Florian Imkamp, Thomas R W Herrmann, Hossein Tezval, Mario W Kramer, Sven Perner, Axel S Merseburger
A range of new treatment options has recently become available for patients with advanced metastatic castration-resistant prostate cancer (mCRPC). Androgen deprivation therapy (ADT) with luteinizing hormone-releasing hormone is continued when performing chemotherapy or androgen deprivation with new second-generation therapeutic agents such as enzalutamide or abiraterone acetate. Despite the fact that free testosterone (FT) is the biologically active form, it is common practice that androgen suppression is monitored via total testosterone levels only...
January 2017: Oncology Letters
https://www.readbyqxmd.com/read/28107595/chromogranin-a-and-neurone-specific-enolase-variations-during-the-first-three-months-of-abiraterone-therapy-predict-outcomes-in-patients-with-metastatic-castration-resistant-prostate-cancer
#14
Liancheng Fan, Yanqing Wang, Chi Chenfei, Jiahua Pan, Xun Shangguan, Zhixiang Xin, Jianian Hu, Zhou Lixin, Baijun Dong, Wei Xue
OBJECTIVE: To determine the prognostic factors of circulating chromogranin A (CgA) and neurone-specific enolase (NSE) variations during the first 3 months of abiraterone Acetate (AA) treatment in metastatic castration-resistant prostate cancer (mCRPC) patients. PATIENTS AND METHODS: The serum levels of CgA, NSE were measured at baseline and after 3 months of AA treatments in 40 mCRPC patients. Outcome measures were PSA progression-free survival (PSA-PFS), radiographic PFS (rPFS) and overall survival (OS)...
January 20, 2017: BJU International
https://www.readbyqxmd.com/read/28103574/68ga-psma-11-pet-ct-for-prostate-cancer-staging-and-risk-stratification-in-chinese-patients
#15
Shiming Zang, Guoqiang Shao, Can Cui, Tian-Nv Li, Yue Huang, Xiaochen Yao, Qiu Fan, Zejun Chen, Jin Du, Ruipeng Jia, Hongbin Sun, Zichun Hua, Jun Tang, Feng Wang
We evaluated the clinical utility of 68Ga-PSMA-11 PET/CT for staging and risk stratification of treatment-naïve prostate cancer (PCa) and metastatic castrate-resistant prostate cancer (mCRPC). Twenty-two consecutive patients with treatment-naïve PCa and 18 with mCRPC were enrolled. 68Ga-PSMA-11 PET/CT and magnetic resonance imaging (MRI) were performed for the evaluation of primary prostatic lesions, and bone scans were used for evaluation bone metastasis. Among the 40 patients, 37 (92.5% [22 treatment-naïve PCa, 15 mCRPC]) showed PSMA-avid lesions on 68Ga-PSMA-11 images...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28096932/contemporary-agents-in-the-management-of-metastatic-castration-resistant-prostate-cancer
#16
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
#17
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
#18
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
#19
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
#20
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
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