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Treatment resistant mCRPC

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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
#1
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
#2
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
#3
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/29126389/safety-and-efficacy-of-abiraterone-acetate-in-chemotherapy-naive-patients-with-metastatic-castration-resistant-prostate-cancer-an-italian-multicenter-real-life-study
#4
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/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
#5
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
#6
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/29102858/weekly-cabazitaxel-plus-prednisone-is-effective-and-less-toxic-for-unfit-metastatic-castration-resistant-prostate-cancer-phase-ii-spanish-oncology-genitourinary-group-sogug-trial
#7
Miguel Ángel Climent, Begoña Pérez-Valderrama, Begoña Mellado, Eva María Fernández Parra, Ovidio Fernández Calvo, María Ochoa de Olza, Laura Muinelo Romay, Urbano Anido, Montserrat Domenech, Susana Hernando Polo, José Ángel Arranz Arija, Cristina Caballero, María José Juan Fita, Daniel Castellano
AIM: Cabazitaxel (CBZ), a novel tubulin-binding taxane, improves overall survival in metastatic castration-resistant prostate cancer (mCRPC) that progresses during or after docetaxel treatment. We have designed a phase II study to evaluate the efficacy and safety of CBZ as a weekly schedule for 'unfit' mCRPC patients after docetaxel failure. METHODS: In this single arm phase II study. CBZ was weekly administered in 1-hour infusion on days 1, 8, 15 and 22, every 5 weeks at 10 mg/m(2) to eligible 'unfit' patients; oral prednisone (5 mg) was administered twice a day...
November 2, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29101113/treatment-of-advanced-prostate-cancer-a-review-of-current-therapies-and-future-promise
#8
Semini Sumanasuriya, Johann De Bono
Despite many recent advances in the therapy for metastatic castration-resistant prostate cancer (mCRPC), the disease remains incurable, although men suffering from this disease are living considerably longer. In this review, we discuss the current treatment options available for this disease, such as taxane-based chemotherapy, the novel hormone therapies abiraterone and enzalutamide, and treatments such as radium-223 and sipuleucel-T. We also highlight the need for ongoing research in this field, because, despite numerous recent advances, the prognosis for mCRPC remains poor...
November 3, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/29098556/selection-and-monitoring-of-patients-with-metastatic-castration-resistant-prostate-cancer-for-treatment-with-radium-223
#9
REVIEW
A Rodriguez-Vida, M D Torregrosa, Á Pinto, M Á Climent, D Olmos, J Carles
Despite the improvement provided by androgenic suppression in the treatment of prostate cancer, most of tumors develop resistance to castration. However, new therapies have demonstrated an increase in patient survival such as radium-223 (Ra-223), an alpha emitter and calcium mimetic with the capability of targeting osteoblastic metastatic lesions. According to results of the ALSYMPCA phase III trial, Ra-223 has demonstrated its activity by improving symptoms and survival of patients with metastatic castration-resistant prostate cancer (mCRPC), symptomatic bone metastases, and no known visceral metastatic disease, without interfering with subsequent treatments...
November 2, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/29096157/the-association-between-health-related-quality-of-life-scores-and-clinical-outcomes-in-metastatic-castration-resistant-prostate-cancer-patients-exploratory-analyses-of-affirm-and-prevail-studies
#10
Tomasz M Beer, Kurt Miller, Bertrand Tombal, David Cella, De Phung, Stefan Holmstrom, Cristina Ivanescu, Konstantina Skaltsa, Shevani Naidoo
BACKGROUND: Our exploratory analysis examined the association between health-related quality of life (HRQoL) (baseline and change over time) and clinical outcomes (overall survival [OS]/radiographic progression-free survival [rPFS]) in metastatic castration-resistant prostate cancer (mCRPC). METHODS: HRQoL, OS and rPFS were assessed in phase III trials comparing enzalutamide with placebo in chemotherapy-naïve (PREVAIL; NCT01212991) or post-chemotherapy (AFFIRM; NCT00974311) mCRPC...
October 30, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29079165/the-contemporary-use-of-radium-223-in-metastatic-castration-resistant-prostate-cancer
#11
Daniel Heinrich, Jasmin Bektic, Andries M Bergman, Orazio Caffo, Richard Cathomas, Kim N Chi, Gedske Daugaard, Daniel Keizman, Jon Kindblom, Gero Kramer, David Olmos, Aurelius Omlin, Srikala S Sridhar, Marcello Tucci, Inge van Oort, Sten Nilsson
Radium-223 dichloride (radium-223) was approved for the treatment of patients with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases in the United States and Europe in 2013. This followed a reported overall survival benefit for patients treated with radium-223 and best standard of care (BSoC) when compared with placebo and BSoC in the ALpharadin in SYMptomatic Prostate CAncer (ALSYMPCA) trial. At that time, docetaxel was the standard first-line choice for patients with metastatic CRPC (mCRPC)...
September 6, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29074061/anticancer-activity-and-tolerance-of-treatments-received-beyond-progression-in-men-treated-upfront-with-androgen-deprivation-therapy-with-or-without-docetaxel-for-metastatic-castration-na%C3%A3-ve-prostate-cancer-in-the-getug-afu-15-phase-3-trial
#12
Pernelle Lavaud, Gwenaëlle Gravis, Stéphanie Foulon, Florence Joly, Stéphane Oudard, Frank Priou, Igor Latorzeff, Loïc Mourey, Michel Soulié, Remy Delva, Ivan Krakowski, Brigitte Laguerre, Christine Théodore, Jean Marc Ferrero, Philippe Beuzeboc, Muriel Habibian, Frédéric Rolland, Gael Deplanque, Damien Pouessel, Sylvie Zanetta, Jean François Berdah, Jerome Dauba, Marjorie Baciuchka, Christian Platini, Claude Linassier, Nicole Tubiana-Mathieu, Jean Pascal Machiels, Claude El Kouri, Alain Ravaud, Etienne Suc, Jean Christophe Eymard, Ali Hasbini, Guilhem Bousquet, Stéphane Culine, Jean-Marie Boher, Gabrielle Tergemina-Clain, Clémence Legoupil, Karim Fizazi
BACKGROUND: Androgen deprivation therapy (ADT) plus docetaxel is the standard of care in fit men with metastatic castration-naive prostate cancer (mCNPC) following results from GETUG-AFU 15, CHAARTED, and STAMPEDE. No data are available on the efficacy of treatments used for metastatic castration-resistant prostate cancer (mCRPC) in men treated upfront with ADT plus docetaxel for mCNPC. OBJECTIVE: To investigate the efficacy and tolerance of subsequent treatments in patients treated upfront with chemo-hormonal therapy for mCNPC...
October 23, 2017: European Urology
https://www.readbyqxmd.com/read/29071398/-metastatic-castration-resistant-prostate-cancer-use-of-cabazitaxel-taking-into-consideration-current-data
#13
J E Gschwend, P Albers, M Bögemann, P Goebell, A Heidenreich, J Klier, F König, S Machtens, K Pantel, C Thomas
BACKGROUND: At the 2016 ASCO annual meeting, new data from two randomized phase III studies concerning taxane-based chemotherapy as a treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC) were presented. OBJECTIVES: The focus is on the clinical impact of these data. MATERIALS AND METHODS: A group of German experts in the field of urogenital-oncologic expertise discussed the clinical impact with respect to the current data...
October 25, 2017: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/29069718/androgen-receptor-amplification-is-concordant-between-circulating-tumor-cells-and-biopsies-from-men-undergoing-treatment-for-metastatic-castration-resistant-prostate-cancer
#14
Jennifer Podolak, Kristi Eilers, Timothy Newby, Rachel Slottke, Erin Tucker, Susan B Olson, Hui-Wen Lue, Jack Youngren, Rahul Aggarwal, Eric J Small, Julie N Graff, Joshi J Alumkal, Tomasz M Beer, George V Thomas
Increased AR activity has been shown to be preserved in spatially distinct metastatic tumors from the same patient suggesting the requirement for lineage-specific dependencies for metastatic castration resistant prostate cancer (mCRPC). Amplification of the AR gene is a common mechanism by which mCRPC increase AR activity. To determine whether AR amplification in circulating tumor cells (CTC) could complement metastatic tissue biopsies in men undergoing treatment for mCRPC, we developed a novel two-step assay to isolate CTCs and subsequently analyzed AR amplification status in CTCs and matched biopsy tissue from the same patient by fluorescence in situ hybridization (FISH)...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29069303/a-prospective-genome-wide-study-of-prostate-cancer-metastases-reveals-association-of-wnt-pathway-activation-and-increased-cell-cycle-proliferation-with-primary-resistance-to-abiraterone-acetate-prednisone
#15
L Wang, S M Dehm, D W Hillman, H Sicotte, W Tan, M Gormley, V Bhargava, R Jimenez, F Xie, P Yin, S Qin, F Quevedo, B A Costello, H C Pitot, T Ho, A H Bryce, Z Ye, Y Li, P Eiken, P T Vedell, P Barman, B P McMenomy, T D Atwell, R E Carlson, M Ellingson, B Eckloff, R Qin, F Ou, S N Hart, H Huang, J Jen, E D Wieben, K R Kalari, R M Weinshilboum, L Wang, M Kohli
Background: Genomic aberrations have been identified in metastatic castration-resistant prostate cancer (mCRPC), but molecular predictors of resistance to abiraterone acetate/prednisone (AA/P) treatment are not known. Patients and Methods: In a prospective clinical trial, mCRPC patients underwent whole exome sequencing (n = 82) and RNA-sequencing (n = 75) of metastatic biopsies before initiating AA/P with the objective of identifying genomic alterations associated with resistance to AA/P...
October 23, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29063869/role-of-chemotherapy-in-prostate-cancer
#16
REVIEW
Rita Nader, Joelle El Amm, Jeanny B Aragon-Ching
Chemotherapy in prostate cancer (PCa) has undergone dramatic landscape changes. While earlier studies utilized varying chemotherapy regimens which were found to be largely palliative in nature and hardly resulted in durable or meaningful responses, docetaxel resulted in the first chemotherapy agent that showed improvement in overall survival in metastatic castration-resistant prostate cancer (mCRPC). However, combination chemotherapy or any agents added to docetaxel have failed to yield incremental benefits...
October 20, 2017: Asian Journal of Andrology
https://www.readbyqxmd.com/read/29063171/-neuroendocrine-prostate-cancer
#17
S Tritschler, R Erdelkamp, C Stief, M Hentrich
Neuroendocrine prostate cancer (NEPC) mostly occurs as a treatment-emergent adaptive response under the pressure of intensive androgen deprivation treatment (t-NEPC). Approximately 30-40% of patients with metastatic castration-resistant prostate cancer (mCRPC) also have neuroendocrine involvement. In contrast primary small cell prostate cancer is very rare (<1%). A t‑NEPC should be clinically suspected in patients who have particularly aggressive mCRPC but a disproportionately low prostate-specific antigen (PSA) level and elevated neuroendocrine tumor markers, such as chromogranin A and neuron-specific enolase...
November 2017: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/29046247/optimal-usage-of-radium-223-in-metastatic-castration-resistant-prostate-cancer
#18
REVIEW
Tai-Lung Cha, Tony Tong-Lin Wu, Nicholas John Vogelzang, Chao-Yuan Huang, Shu-Pin Huang, Chia-Chi Lin, Yen-Chuan Ou, See-Tong Pang, Daniel Heung-Yuan Shen, Wen-Jeng Wu, Wayne Yen-Hwa Chang
Radium-223 is a first-in-class α-emitting radiopharmaceutical that targets bone metastases associated with metastatic castration-resistant prostate cancer (mCRPC). In the pivotal phase III trial ALSYMPCA, radium-223 significantly increased overall survival (OS), compared with placebo (median 14.9 vs 11.3 months; hazard ratio 0.70; 95% CI 0.58-0.83; p < 0.001), in patients with mCRPC and symptomatic bone metastases-with a comparable safety profile. To optimize treatment outcomes, selection of appropriate patients is important...
November 2017: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/29032717/bet-inhibitors-in-metastatic-prostate-cancer-therapeutic-implications-and-rational-drug-combinations
#19
Mark C Markowski, Angelo M De Marzo, Emmanuel S Antonarakis
The bromodomain and extra-terminal (BET) family of proteins are epigenetic readers of acetylated histones regulating a vast network of protein expression across many different cancers. Therapeutic targeting of BET is an attractive area of clinical development for metastatic castration-resistant prostate cancer (mCRPC), particularly due to its putative effect on c-MYC expression and its interaction with the androgen receptor (AR). Areas covered: We speculate that a combination approach using inhibitors of BET proteins (BETi) with other targeted therapies may be required to improve the therapeutic index of BET inhibition in the management of prostate cancer...
October 27, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28986618/-177-lu-psma-therapy-current-evidence-for-use-in-the-treatment-of-patients-with-metastatic-prostate-cancer
#20
REVIEW
M Boegemann, A J Schrader, K Rahbar
BACKGROUND: Despite significant progress in the treatment of metastatic castration-resistant prostate cancer (mCRPC) in recent years (including agents targeting androgen receptor signaling, chemotherapy, and (223)Ra), most of these patients still succumb to prostate cancer. Recently, (177)lutetium prostate-specific membrane antigen radioligand therapy ((177)Lu-PSMA-RLT) has been increasingly used within compassionate use provisions in these patients in Germany and showed promising efficacy...
November 2017: Der Urologe. Ausg. A
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