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https://www.readbyqxmd.com/read/28345444/budgetary-impact-of-cabazitaxel-use-after-docetaxel-treatment-for-metastatic-castration-resistant-prostate-cancer
#1
Kyle Flannery, Ed Drea, Louis Hudspeth, Shelby Corman, Xin Gao, Mei Xue, Raymond Miao
BACKGROUND: With the approval of several new treatments for metastatic castration-resistant prostate cancer (mCRPC), budgetary impact is a concern for health plan decision makers. Budget impact models (BIMs) are becoming a requirement in many countries as part of formulary approval or reimbursement decisions. Cabazitaxel is a second-generation taxane developed to overcome resistance to docetaxel and is approved for the treatment of patients with mCRPC previously treated with a docetaxel-containing regimen...
April 2017: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/28342983/lipid-quantification-by-raman-microspectroscopy-as-a-potential-biomarker-in-prostate-cancer
#2
Jordan O'Malley, Rahul Kumar, Andrey Kuzmin, Artem Pliss, Neelu Yadav, Srimmitha Balachandar, Jianmin Wang, Kristopher Attwood, Paras N Prasad, Dhyan Chandra
Metastatic castration recurrent prostate cancer (mCRPC) remains incurable and is one of the leading causes of cancer-related death among American men. Therefore, detection of prostate cancer (PCa) at early stages may reduce PCa-related mortality in men. We show that lipid quantification by vibrational Raman Microspectroscopy and Biomolecular Component Analysis may serve as a potential biomarker in PCa. Transcript levels of lipogenic genes including sterol regulatory element-binding protein-1 (SREBP-1) and its downstream effector fatty acid synthase (FASN), and rate-limiting enzyme acetyl CoA carboxylase (ACACA) were upregulated corresponding to both Gleason score and pathologic T stage in the PRAD TCGA cohort...
March 23, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28321130/effective-combinatorial-immunotherapy-for-castration-resistant-prostate-cancer
#3
Xin Lu, James W Horner, Erin Paul, Xiaoying Shang, Patricia Troncoso, Pingna Deng, Shan Jiang, Qing Chang, Denise J Spring, Padmanee Sharma, John A Zebala, Dean Y Maeda, Y Alan Wang, Ronald A DePinho
A significant fraction of patients with advanced prostate cancer treated with androgen deprivation therapy experience relapse with relentless progression to lethal metastatic castration-resistant prostate cancer (mCRPC). Immune checkpoint blockade using antibodies against cytotoxic-T-lymphocyte-associated protein 4 (CTLA4) or programmed cell death 1/programmed cell death 1 ligand 1 (PD1/PD-L1) generates durable therapeutic responses in a significant subset of patients across a variety of cancer types. However, mCRPC showed overwhelming de novo resistance to immune checkpoint blockade, motivating a search for targeted therapies that overcome this resistance...
March 20, 2017: Nature
https://www.readbyqxmd.com/read/28319807/targeting-nf-kappa-b-signaling-by-artesunate-restores-sensitivity-of-castrate-resistant-prostate-cancer-cells-to-antiandrogens
#4
Jessica J Nunes, Swaroop K Pandey, Anjali Yadav, Sakshi Goel, Bushra Ateeq
Androgen deprivation therapy (ADT) is the most preferred treatment for men with metastatic prostate cancer (PCa). However, the disease eventually progresses and develops resistance to ADT in majority of the patients, leading to the emergence of metastatic castration-resistant prostate cancer (mCRPC). Here, we assessed artesunate (AS), an artemisinin derivative, for its anticancer properties and ability to alleviate resistance to androgen receptor (AR) antagonists. We have shown AS in combination with bicalutamide (Bic) attenuates the oncogenic properties of the castrate-resistant (PC3, 22RV1) and androgen-responsive (LNCaP) PCa cells...
March 16, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28318331/docetaxel-chemotherapy-in-metastatic-castration-resistant-prostate-cancer-cost-of-care-in-medicare-and-commercial-populations
#5
A Armstrong, C Bui, K Fitch, T Goss Sawhney, B Brown, S Flanders, M Balk, J Deangelis, J Chambers
OBJECTIVE: To estimate the healthcare costs and characteristics of docetaxel chemotherapy episodes of care for men with metastatic castration-resistant prostate cancer (mCRPC). METHODS: We used Medicare 5% sample and MarketScan® Commercial (2010 - 2013) claims data sets to identify men with mCRPC and initial episodes of docetaxel treatment. Docetaxel episodes included docetaxel claim costs from the first claim until 30 days after the last claim, with earlier termination for death, insurance disenrollment, or the end of a 24-month look-forward period from initial docetaxel index date...
March 20, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28314838/a-phase-i-study-of-abiraterone-acetate-combined-with-bez235-a-dual-pi3k-mtor-inhibitor-in-metastatic-castration-resistant-prostate-cancer
#6
Xiao X Wei, Andrew C Hsieh, Won Kim, Terence Friedlander, Amy M Lin, Mirela Louttit, Charles J Ryan
LESSONS LEARNED: The combination of standard dose abiraterone acetate and BEZ235, a pan-class I PI3K and mTORC1/2 inhibitor, was poorly tolerated in men with progressive mCRPC.Although the clinical development of BEZ235 has been discontinued in prostate cancer, agents that more selectively target PI3K-AKT-mTOR signaling may have a more favorable therapeutic index and should continue to be explored. BACKGROUND: Androgen receptor (AR) and phosphatidylinositol-3 kinase (PI3K) signaling are two commonly perturbed pathways in prostate cancer...
March 17, 2017: Oncologist
https://www.readbyqxmd.com/read/28314611/clinical-outcomes-from-androgen-signaling-directed-therapy-after-treatment-with-abiraterone-acetate-and-prednisone-in-patients-with-metastatic-castration-resistant-prostate-cancer-post-hoc-analysis-of-cou-aa-302
#7
Matthew R Smith, Fred Saad, Dana E Rathkopf, Peter F A Mulders, Johann S de Bono, Eric J Small, Neal D Shore, Karim Fizazi, Thian Kheoh, Jinhui Li, Peter De Porre, Mary B Todd, Margaret K Yu, Charles J Ryan
In the COU-AA-302 trial, abiraterone acetate plus prednisone significantly increased overall survival for patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). Limited information exists regarding response to subsequent androgen signaling-directed therapies following abiraterone acetate plus prednisone in patients with mCRPC. We investigated clinical outcomes associated with subsequent abiraterone acetate plus prednisone (55 patients) and enzalutamide (33 patients) in a post hoc analysis of COU-AA-302...
March 14, 2017: European Urology
https://www.readbyqxmd.com/read/28302580/the-role-of-therapeutic-layering-in-optimizing-treatment-for-patients-with-castration-resistant-prostate-cancer-radar-ii
#8
E David Crawford, Daniel P Petrylak, Neal Shore, Fred Saad, Susan F Slovin, Nicholas J Vogelzang, Thomas E Keane, Phillip J Koo, Leonard G Gomella, Joe M O'Sullivan, Bertrand Tombal, Raoul S Concepcion, Paul Sieber, Nelson N Stone, Steven E Finkelstein, Evan Y Yu
OBJECTIVE: To offer recommendations on identification of disease progression, treatment management strategies, and suggestions on timing of initiating and discontinuing specific CRPC treatments. MATERIALS AND METHODS: The RADAR II [Prostate Cancer Radiographic Assessments for Detection of Advanced Recurrence] Working Group convened to provide guidance on sequencing, combination, or layering of approved treatments for mCRPC based on available data and clinical experience...
March 13, 2017: Urology
https://www.readbyqxmd.com/read/28278075/piecing-the-puzzle-together-docetaxel-cycles-and-current-considerations-in-the-treatment-of-metastatic-castration-resistant-prostate-cancer
#9
Hannah E Feinman, Douglas K Price, William D Figg
Docetaxel is the current first line therapy for metastatic castration-resistant prostate cancer (mCRPC), but there is no standard number of docetaxel cycles given to patients. In their post hoc analysis of the Mainsail study, de Morrée et al. show that the number of docetaxel cycles administered to a patient is a significant factor contributing to overall survival. These findings warrant further investigation into the standardization of the number of docetaxel cycles administered.
February 25, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28277852/the-treatment-patterns-of-castration-resistant-prostate-cancer-in-japan-including-symptomatic-skeletal-events-and-associated-treatment-and-healthcare-resource-use
#10
Hiroji Uemura, Marco DiBonaventura, Ed Wang, Dianne Athene Ledesma, Kristen Concialdi, Yasuko Aitoku
BACKGROUND: Real-world treatment patterns of bone metastatic castration-resistant prostate cancer (mCRPC) in Japan were examined, focusing on treatment patterns and resource use differences attributed to symptomatic skeletal events (SSEs). METHODS: Urologists (N=176) provided retrospective chart data for patients with mCRPC (N=445) via online surveys. Descriptive analyses and chi-square tests evaluated treatment patterns and their differences by SSE presence; generalized linear mixed models examined healthcare resource utilization differences as a function of SSEs...
March 6, 2017: Expert Review of Pharmacoeconomics & Outcomes Research
https://www.readbyqxmd.com/read/28263212/a-phase-1-trial-of-cabazitaxel-combined-with-188-re-hydroxyethylidene-diphosphonate-in-patients-with-metastatic-castration-resistant-prostate-cancer-who-progressed-on-or-after-a-docetaxel-containing-treatment-the-recab-trial
#11
Joyce M van Dodewaard-de Jong, Esther W Bouman-Wammes, Haiko J Bloemendal, Henk M W Verheul, John M H de Klerk, Alfons J M van den Eertwegh
PURPOSE: In patients with metastatic castration-resistant prostate cancer (mCRPC), bone-seeking radiopharmaceuticals, such as Re-hydroxyethylidene diphosphonate (HEDP), are effective for pain palliation and have a marked antitumor effect. Cabazitaxel is the standard second-line chemotherapy for mCRPC patients. We performed a phase 1 study investigating the safety and feasibility of the combined treatment with Re-HEDP and cabazitaxel in mCRPC patients. METHODS: Patients with mCRPC and documented disease progression on or after docetaxel were eligible for inclusion...
March 3, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28259476/treatment-outcomes-and-tumor-loss-of-heterozygosity-in-germline-dna-repair-deficient-prostate-cancer
#12
Matti Annala, Werner J Struss, Evan W Warner, Kevin Beja, Gillian Vandekerkhove, Amanda Wong, Daniel Khalaf, Irma-Liisa Seppälä, Alan So, Gregory Lo, Rahul Aggarwal, Eric J Small, Matti Nykter, Martin E Gleave, Kim N Chi, Alexander W Wyatt
BACKGROUND: Germline mutations in DNA repair genes were recently reported in 8-12% of patients with metastatic castration-resistant prostate cancer (mCRPC). It is unknown whether these mutations associate with differential response to androgen receptor (AR)-directed therapy. OBJECTIVE: To determine the clinical response of mCRPC patients with germline DNA repair defects to AR-directed therapies and to establish whether biallelic DNA repair gene loss is detectable in matched circulating tumor DNA (ctDNA)...
March 1, 2017: European Urology
https://www.readbyqxmd.com/read/28258960/which-factors-predict-overall-survival-in-patients-with-metastatic-castration-resistant-prostate-cancer-treated-with-abiraterone-acetate-post-docetaxel
#13
Charles Van Praet, Sylvie Rottey, Fransien Van Hende, Gino Pelgrims, Wim Demey, Filip Van Aelst, Wim Wynendaele, Thierry Gil, Peter Schatteman, Bertrand Filleul, Denis Schallier, Jean-Pascal Machiels, Dirk Schrijvers, Els Everaert, Lionel D'Hondt, Patrick Werbrouck, Joanna Vermeij, Jeroen Mebis, Marylene Clausse, Marika Rasschaert, Joanna Van Erps, Jolanda Verheezen, Jan Van Haverbeke, Jean-Charles Goeminne, Nicolaas Lumen
BACKGROUND: Abiraterone acetate (AA) increases overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel. However, survival time varies substantially between individuals. Our goal was to identify prognostic factors that better estimate OS. MATERIALS AND METHODS: This is a retrospective multicentric analysis of 368 patients with mCRPC starting AA with prednisone after docetaxel. Cox proportional hazards statistics were applied...
February 1, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28239558/role-of-androgen-receptor-splice-variants-in-prostate-cancer-metastasis
#14
Jin Xu, Yun Qiu
Prostate cancer (PCa) is one of the most lethal cancers in western countries. Androgen receptor (AR) signaling pathway plays a key role in PCa progression. Despite the initial effectiveness of androgen deprivation therapy (ADT) for treatment of patients with advanced PCa, most of them will develop resistance to ADT and progress to metastatic castration resistant prostate cancer (mCRPC). Constitutively transcriptional activated AR splice variants (AR-Vs) have emerged as critical players in the development and progression of mCRPC...
October 2016: Asian J Urol
https://www.readbyqxmd.com/read/28219796/simultaneous-quantitation-of-abiraterone-enzalutamide-n-desmethyl-enzalutamide-and-bicalutamide-in-human-plasma-by-lc-ms-ms
#15
Kyu-Pyo Kim, Robert A Parise, Julianne L Holleran, Lionel D Lewis, Leonard Appleman, Nielka van Erp, Michael J Morris, Jan H Beumer
Inhibiting the androgen receptor (AR) pathway is an important clinical strategy in metastatic prostate cancer. Novel agents including abiraterone acetate and enzalutamide have been shown to prolong life in men with metastatic, castration-resistant prostate cancer (mCRPC). To evaluate the pharmacokinetics of AR-targeted agents, we developed and validated an LC-MS/MS assay for the quantitation of enzalutamide, N-desmethyl enzalutamide, abiraterone and bicalutamide in 0.05mL human plasma. After protein precipitation, chromatographic separation was achieved with a Phenomenex Synergi Polar-RP column and a linear gradient of 0...
May 10, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28217987/radiolabeled-prostate-specific-membrane-antigen-small-molecule-inhibitors
#16
Leon Will, Ida Sonni, Klaus Kopka, Clemens Kratochwil, Frederik L Giesel, Uwe Haberkorn
Prostate cancer (PC) is one of the most common malignancies worldwide. Prostate-specific membrane antigen (PSMA) has been found to be expressed in most PCs and represents an ideal target for diagnostic and therapeutic purposes. Numerous PSMA tracers have been recently developed. This review aims to provide an overview on the clinical influence of PSMA tracers in primary staging, biochemical recurrence (BCR) of PC and advanced, metastatic PC. Additionally, the use of PSMA tracers in systemic radioligand therapy (RLT) of metastatic castration-resistant prostate cancer (mCRPC), as well as non-prostatic specific uptake of PSMA tracers and the use of PSMA imaging to manage therapy have been described...
June 2017: Quarterly Journal of Nuclear Medicine and Molecular Imaging
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
#17
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
#18
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/28212321/therapeutic-approaches-targeting-myc-driven-prostate-cancer
#19
REVIEW
Richard J Rebello, Richard B Pearson, Ross D Hannan, Luc Furic
The transcript encoding the proto-oncogene MYC is commonly overexpressed in prostate cancer (PC). MYC protein abundance is also increased in the majority of cases of advanced and metastatic castrate-resistant PC (mCRPC). Accordingly, the MYC-directed transcriptional program directly contributes to PC by upregulating the expression of a number of pro-tumorigenic factors involved in cell growth and proliferation. A key cellular process downstream of MYC activity is the regulation of ribosome biogenesis which sustains tumor growth...
February 16, 2017: Genes
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
#20
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
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