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https://www.readbyqxmd.com/read/29237083/relationship-between-patient-reported-outcomes-and-clinical-outcomes-in-metastatic-castration-resistant-prostate-cancer-post-hoc-analysis-of-cou-aa-301-and-cou-aa-302
#1
D Cella, S Traina, T Li, K Johnson, K F Ho, A Molina, N D Shore
Background: Patient-reported outcomes (PROs) are used to assess benefit-risk in drug development. The relationship between PROs and clinical outcomes is not well understood. We aimed to elucidate the relationships between changes in PRO measures and clinical outcomes in metastatic castration-resistant prostate cancer (mCRPC). Patients and methods: We investigated relationships between changes in self-reported fatigue, pain, functional well-being (FWB), physical well-being (PWB) and prostate cancer-specific symptoms with overall survival (OS) and radiographic progression-free survival (rPFS) after 6 and 12 months of treatment in COU-AA-301 (N = 1195) or COU-AA-302 (N = 1088)...
December 11, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29230006/platinum-sensitivity-in-metastatic-prostate-cancer-does-histology-matter
#2
Michael S Humeniuk, Rajan T Gupta, Patrick Healy, Megan McNamara, Sundhar Ramalingam, Michael Harrison, Daniel George, Tian Zhang, Yuan Wu, Andrew J Armstrong
BACKGROUND: Platinum-based chemotherapy is effective in men with neuroendocrine prostate cancer (NEPC), but it is unclear whether histology (adenocarcinoma vs. non-adenocarcinoma NEPC variants) is predictive of platinum sensitivity. Given that NEPC exists as a spectrum, there may be men with adenocarcinoma who might benefit from platinum chemotherapy, particularly those men with DNA repair defects. METHODS: This was a retrospective study of all of the men seen at Duke University since 2005 who had metastatic castration-resistant prostate cancer (mCRPC) and were treated with a platinum agent...
December 11, 2017: Prostate Cancer and Prostatic Diseases
https://www.readbyqxmd.com/read/29222530/seizure-rates-in-enzalutamide-treated-men-with-metastatic-castration-resistant-prostate-cancer-and-risk-of-seizure-the-upward-study
#3
Susan Slovin, William Clark, Joan Carles, Andrew Krivoshik, Jung Wook Park, Fong Wang, Daniel George
Importance: The androgen receptor inhibitor enzalutamide prolongs survival in men with metastatic castration-resistant prostate cancer (mCRPC). In controlled clinical studies, 0.5% (10 of 2051) of patients experienced seizure, but patients with a history of or risk factors for seizure were excluded. Men with mCRPC and seizure risk factors have an estimated seizure rate of 2.8 per 100 patient-years without enzalutamide exposure. Objective: To assess seizure incidence in patients with seizure risk factors who were receiving enzalutamide for mCRPC...
December 7, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/29206995/concordance-of-circulating-tumor-dna-and-matched-metastatic-tissue-biopsy-in-prostate-cancer
#4
Alexander W Wyatt, Matti Annala, Rahul Aggarwal, Kevin Beja, Felix Feng, Jack Youngren, Adam Foye, Paul Lloyd, Matti Nykter, Tomasz M Beer, Joshi J Alumkal, George V Thomas, Robert E Reiter, Matthew B Rettig, Christopher P Evans, Allen C Gao, Kim N Chi, Eric J Small, Martin E Gleave
Background: Real-time knowledge of the somatic genome can influence management of patients with metastatic castration-resistant prostate cancer (mCRPC). While routine metastatic tissue biopsy is challenging in mCRPC, plasma circulating tumor DNA (ctDNA) has emerged as a minimally invasive tool to sample the tumor genome. However, no systematic comparisons of matched "liquid" and "solid" biopsies have been performed that would enable ctDNA profiling to replace the need for direct tissue sampling...
December 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29191639/population-based-analysis-of-treatment-toxicity-among-men-with-castration-resistant-prostate-cancer-a-phase-iv-study
#5
Christopher J D Wallis, Raj Satkunasivam, Refik Saskin, Symron Bansal, Girish S Kulkarni, Urban Emmenegger, Robert K Nam
OBJECTIVE: To assess the toxicity and effectiveness of contemporary metastatic castrate-resistant prostate cancer (mCRPC) treatments at a population-level, among all patients in Ontario particularly treated with newer agents including abiraterone, enzalutamide, docetaxel and cabazitaxel. METHODS: We performed a population-based, retrospective cohort study of 2439 men aged ≥65 years treated for mCRPC with abiraterone, enzalutamide, docetaxel, or cabazitaxel from 2003-2015 in Ontario, Canada...
November 27, 2017: Urology
https://www.readbyqxmd.com/read/29187435/evaluating-metformin-as-a-potential-chemosensitizing-agent-when-combined-with-docetaxel-chemotherapy-in-castration-resistant-prostate-cancer-cells
#6
Michelle J Mayer, Laurence H Klotz, Vasundara Venkateswaran
BACKGROUND/AIM: Docetaxel, the first-line chemotherapy for metastatic castration-resistant prostate cancer (mCRPC), provides certain survival benefits, but is associated with significant toxicity. A novel therapeutic approach for mCRPC is combining docetaxel with a chemosensitizing agent. We hypothesized that metformin, a potential chemosensitizer, would improve docetaxel efficacy in CRPC cells. MATERIALS AND METHODS: MTS assays were used to determine the effect of metformin-docetaxel treatment on PC3 and DU145 cell viability...
December 2017: Anticancer Research
https://www.readbyqxmd.com/read/29185010/preliminary-results-on-response-assessment-using-68ga-hbed-cc-psma-pet-ct-in-patients-with-metastatic-prostate-cancer-undergoing-docetaxel-chemotherapy
#7
Anna Katharina Seitz, Isabel Rauscher, Bernhard Haller, Markus Krönke, Sophia Luther, Matthias M Heck, Thomas Horn, Jürgen E Gschwend, Markus Schwaiger, Matthias Eiber, Tobias Maurer
PURPOSE: To investigate the value of 68Ga-HBED-CC PSMA (68Ga-PSMA) PET/CT for response assessment in metastatic castration-sensitive and castration-resistant prostate cancer (mCSPC and mCRPC) during docetaxel chemotherapy. METHODS: 68Ga-PSMA PET/CT was performed in seven mCSPC patients before and after six cycles of upfront docetaxel chemotherapy and in 16 mCRPC patients before and after three cycles of palliative docetaxel chemotherapy. Radiographic treatment response was evaluated separately on the 68Ga-PSMA PET and CT datasets...
November 28, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29183960/radium-223-safety-efficacy-and-concurrent-use-with-abiraterone-or-enzalutamide-first-u-s-experience-from-an-expanded-access-program
#8
Oliver Sartor, Nicholas J Vogelzang, Christopher Sweeney, Daniel C Fernandez, Fabio Almeida, Andrei Iagaru, Alan Brown, Matthew R Smith, Manish Agrawal, Adam P Dicker, Jorge A Garcia, Jose Lutzky, Yu-Ning Wong, Oana Petrenciuc, Jeremy Gratt, Neal D Shore, Michael J Morris
BACKGROUND: In the phase III ALSYMPCA trial, metastatic castration-resistant prostate cancer (mCRPC) patients had few prior life-prolonging therapies. Following ALSYMPCA, which demonstrated radium-223 survival benefit, and before radium-223 U.S. commercial availability, an expanded access program (EAP) providing early-access radium-223 allowed life-prolonging therapies in current use. SUBJECTS, MATERIALS, AND METHODS: This phase II, open-label, single-arm, multicenter U...
November 28, 2017: Oncologist
https://www.readbyqxmd.com/read/29164346/impact-of-prior-androgen-receptor-axis-targeted-agents-on-the-clinical-activity-of-subsequent-docetaxel-in-patients-with-metastatic-castration-resistant-prostate-cancer-comparative-assessment-between-abiraterone-acetate-and-enzalutamide
#9
Hideaki Miyake, Yuto Matsushita, Keita Tamura, Daisuke Motoyama, Toshiki Ito, Takayuki Sugiyama, Atsushi Otsuka
The objective of this study was to investigate the impact of prior treatment with androgen receptor-axis-targeted (ARAT) agents, abiraterone acetate (AA) and enzalutamide (Enz), on the activity of subsequently introduced docetaxel in patients with metastatic castration-resistant prostate cancer (mCRPC). This study included a total of 114 mCRPC patients consisting of 54 and 60 who progressed following treatment with AA and Enz, respectively, prior to the introduction of docetaxel, and compared oncological outcomes with docetaxel between these two groups...
November 21, 2017: Medical Oncology
https://www.readbyqxmd.com/read/29163793/rapid-ultra-low-coverage-copy-number-profiling-of-cell-free-dna-as-a-precision-oncology-screening-strategy
#10
Daniel H Hovelson, Chia-Jen Liu, Yugang Wang, Qing Kang, James Henderson, Amy Gursky, Scott Brockman, Nithya Ramnath, John C Krauss, Moshe Talpaz, Malathi Kandarpa, Rashmi Chugh, Missy Tuck, Kirk Herman, Catherine S Grasso, Michael J Quist, Felix Y Feng, Christine Haakenson, John Langmore, Emmanuel Kamberov, Tim Tesmer, Hatim Husain, Robert J Lonigro, Dan Robinson, David C Smith, Ajjai S Alva, Maha H Hussain, Arul M Chinnaiyan, Muneesh Tewari, Ryan E Mills, Todd M Morgan, Scott A Tomlins
Current cell-free DNA (cfDNA) next generation sequencing (NGS) precision oncology workflows are typically limited to targeted and/or disease-specific applications. In advanced cancer, disease burden and cfDNA tumor content are often elevated, yielding unique precision oncology opportunities. We sought to demonstrate the utility of a pan-cancer, rapid, inexpensive, whole genome NGS of cfDNA approach (PRINCe) as a precision oncology screening strategy via ultra-low coverage (~0.01x) tumor content determination through genome-wide copy number alteration (CNA) profiling...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29151928/serum-pre-albumin-predicts-the-clinical-outcome-in-metastatic-castration-resistant-prostate-cancer-patients-treated-with-abiraterone
#11
Liancheng Fan, Chenfei Chi, Sanwei Guo, Yanqing Wang, Wen Cai, Xiaoguang Shao, Fan Xu, Jiahua Pan, Yinjie Zhu, Xun Shangguan, Zhixiang Xin, Jianian Hu, Hongyang Qian, Shaowei Xie, Rui Wang, Lixin Zhou, Baijun Dong, Wei Xue
Objective To determine the prognostic utility of serum pre-albumin in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone (AA). Patients and Methods 112 chemotherapy pretreated or chemotherapy-naive patients were scheduled for systemic treatment with AA. Serum pre-albumin levels were measured before and after 3 months of AA treatment. Univariate and multivariate analyses were performed to determine prognostic factors that were associated with PSA progression-free survival (PSA-PFS), radiographic PFS (rPFS) and overall survival (OS)...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29150561/influence-of-enzalutamide-on-cabazitaxel-pharmacokinetics-a-drug-drug-interaction-study-in-metastatic-castration-resistant-prostate-cancer-mcrpc-patients
#12
Bodine P S Belderbos, Sander Bins, Roelof W F van Leeuwen, Esther Oomen-de Hoop, Nelly van der Meer, Peter de Bruijn, Paul Hamberg, Esther N M Overkleeft, Wendy M van der Deure, Martijn Lolkema, Ronald de Wit, Ron H J Mathijssen
PURPOSE: In ongoing clinical research on metastatic castration-resistant prostate cancer (mCRPC) treatment, the potential enhanced efficacy of the combination of taxanes with AR-targeted agents, i.e. enzalutamide and abiraterone, is currently being explored. Since enzalutamide induces the CYP3A4 enzyme and taxanes are metabolized by this enzyme, a potential drug-drug interaction needs to be investigated. DESIGN: Therefore, we performed a pharmacokinetic cross-over study in mCRPC patients who were scheduled for treatment with cabazitaxel Q3W (25 mg/m(2))...
November 17, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29150328/randomized-phase-2-therapeutic-equivalence-study-of-abiraterone-acetate-fine-particle-formulation-vs-originator-abiraterone-acetate-in-patients-with-metastatic-castration-resistant-prostate-cancer-the-staar-study
#13
Cy A Stein, Richard Levin, Robert Given, Celestia S Higano, Paul Nemeth, Bill Bosch, Jillian Chapas-Reed, Robert Dreicer
BACKGROUND: This multicenter, randomized, open-label, active-controlled study evaluated therapeutic equivalence, steady-state pharmacokinetics, and safety of a novel abiraterone acetate fine particle formulation (AAFP) 500mg plus methylprednisolone vs. the originator AA (OAA) 1000mg plus prednisone in men with metastatic castrate-resistant prostate cancer (mCRPC). The primary endpoint was a comparison of average of serum testosterone levels on treatment days 9 and 10 between groups. METHODS: Men with progressive mCRPC, receiving gonadotropin-releasing hormone agonist or antagonist therapy, and with a serum testosterone level of <50ng/dl were randomized 1:1 to either AAFP 500mg daily plus 4mg methylprednisolone orally twice daily (BID), or OAA 1000mg daily plus 5mg prednisone BID for 84 days...
November 14, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/29138500/circulating-androgen-receptor-combined-with-18f-fluorocholine-pet-ct-metabolic-activity-and-outcome-to-androgen-receptor-signalling-directed-therapies-in-castration-resistant-prostate-cancer
#14
V Conteduca, E Scarpi, P Caroli, S Salvi, C Lolli, S L Burgio, C Menna, G Schepisi, S Testoni, G Gurioli, G Paganelli, V Casadio, F Matteucci, U De Giorgi
The association between choline uptake and androgen receptor (AR) expression is suggested by the upregulation of choline kinase-alpha in prostate cancer. Recently, detection of AR aberration in cell-free DNA as well as early 18F-fluorocholine positron emission tomography/computed tomography (FCH-PET/CT) were associated with outcome in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone and enzalutamide. We aimed to make a direct comparison between circulating AR copy number (CN) and choline uptake at FCH-PET/CT...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29137449/differential-side-effects-profile-in-patients-with-mcrpc-treated-with-abiraterone-or-enzalutamide-a-meta-analysis-of-randomized-controlled-trials
#15
REVIEW
Raphael B Moreira, Marcio Debiasi, Edoardo Francini, Pier V Nuzzo, Guillermo De Velasco, Fernando C Maluf, Andre P Fay, Joaquim Bellmunt, Toni K Choueiri, Fabio A Schutz
Background: Abiraterone and enzalutamide are currently approved for mCRPC patients. Both drugs have distinct mechanisms of action and may have different toxicity profile. There are limited data comparing the side effects of abiraterone and enzalutamide. We performed a meta-analysis of randomized controlled trials (RCT) to better characterize the risk of adverse events associated with both drugs. Methods: We performed a literature search on MEDLINE for studies reporting abiraterone and enzalutamide side effects from January 1966 to July 31, 2015...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29126389/safety-and-efficacy-of-abiraterone-acetate-in-chemotherapy-naive-patients-with-metastatic-castration-resistant-prostate-cancer-an-italian-multicenter-real-life-study
#16
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, Stefano Boccasile, Pasquale Ditonno, Paolo Chiodini, Paolo Verze, Vincenzo Mirone, Luigi Schips
BACKGROUND: To evaluate the safety and efficacy of abiraterone acetate (AA) in the "real life" clinical practice for men with chemotherapy-naïve metastatic castration-resistant prostate. METHODS: A consecutive series of patients with mCRPC in 9 Italian tertiary centres treated with AA was collected. Demographics, clinical parameters, treatment outcomes and toxicity were recorded. The Brief Pain Inventory scale Q3 was tracked and patient treatment satisfaction was evaluated...
November 10, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29123266/sox5-contributes-to-prostate-cancer-metastasis-and-is-a-master-regulator-of-tgf-%C3%AE-induced-epithelial-mesenchymal-transition-through-controlling-twist1-expression
#17
Jieping Hu, Jing Tian, Shimiao Zhu, Libin Sun, Jianpeng Yu, Hao Tian, Qian Dong, Qiang Luo, Ning Jiang, Yuanjie Niu, Zhiqun Shang
BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) is one of the main contributors to the death of prostate cancer patients. To date, the detailed molecular mechanisms underlying mCRPC are unclear. Given the crucial role of epithelial-mesenchymal transition (EMT) in cancer metastasis, we aimed to analyse the expression and function of Transforming growth factor-beta (TGF-β) signal-associated protein named Sox5 in mCRPC. METHODS: The protein expression levels were analysed by western blot, immunohistochemistry and immunofluorescence...
November 9, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29121144/positron-emission-tomography-computed-tomography-based-assessments-of-androgen-receptor-expression-and-glycolytic-activity-as-a-prognostic-biomarker-for-metastatic-castration-resistant-prostate-cancer
#18
Josef J Fox, Somali C Gavane, Estelle Blanc-Autran, Sadek Nehmeh, Mithat Gönen, Brad Beattie, Hebert A Vargas, Heiko Schöder, John L Humm, Samson W Fine, Jason S Lewis, Stephen B Solomon, Joseph R Osborne, Darren Veach, Charles L Sawyers, Wolfgang A Weber, Howard I Scher, Michael J Morris, Steven M Larson
Importance: Androgen receptor-signaling inhibitor (ARSi) drugs prolong life in metastatic castration-resistant prostate cancer (mCRPC), but such tumors eventually become resistant and progress. Comprehensive positron emission tomography/computed tomography (PET/CT) imaging using fluoro-2-D-deoxyglucose F 18 ([18F]-FDG) for glycolysis (Glyc) and fluorodihydrotestosterone F 18 ([18F]-FDHT) for androgen receptor (AR) expression determine heterogeneity of imaging phenotypes, which may be useful in distinguishing patients who will benefit from ARSi drugs from those who need alternative treatments...
November 9, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/29111539/external-validation-and-newly-development-of-a-nomogram-to-predict-overall-survival-of-abiraterone-treated-castration-resistant-patients-with-metastatic-prostate-cancer
#19
Yun-Jie Yang, Guo-Wen Lin, Gao-Xiang Li, Bo Dai, Ding-Wei Ye, Jun-Long Wu, Hu-Yang Xie, Yao Zhu
Abiraterone acetate is approved for the treatment of castration-resistant prostate cancer (CRPC); however, its effects vary. An accurate prediction model to identify patient groups that will benefit from abiraterone treatment is therefore urgently required. The Chi model exhibits a good profile for risk classification, although its utility for the chemotherapy-naive group is unclear. This study aimed to externally validate the Chi model and develop a new nomogram to predict overall survival (OS). We retrospectively analyzed a cohort of 110 patients...
November 7, 2017: Asian Journal of Andrology
https://www.readbyqxmd.com/read/29110971/the-effects-of-enzalutamide-and-abiraterone-on-skeletal-related-events-and-bone-radiological-progression-free-survival-in-castration-resistant-prostate-cancer-patients-an-indirect-comparison-of-randomized-controlled-trials
#20
REVIEW
Sergio Rizzo, Antonio Galvano, Francesco Pantano, Michele Iuliani, Bruno Vincenzi, Francesco Passiglia, Silvia Spoto, Giuseppe Tonini, Viviana Bazan, Antonio Russo, Daniele Santini
Two new drugs, the CYP17 inhibitor abiraterone acetate and the androgen receptor (AR) antagonist enzalutamide, have recently shown to prolong OS prior chemotherapy or in docetaxel treated mCRPC patients, using steroidal therapy or placebo as control group. Updated analyses underlined the role of these new agents on two prostate-specific endpoints as radiographic progression-free survival (rPFS) and time to first skeletal-related event (tSRE). On the basis of these reports, we made an indirect comparison between abiraterone and enzalutamide...
October 16, 2017: Critical Reviews in Oncology/hematology
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