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Treatment resistant mCRPC

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https://www.readbyqxmd.com/read/28548924/comparing-the-clinical-efficacy-of-abiraterone-acetate-enzalutamide-and-orteronel-in-patients-with-metastatic-castration-resistant-prostate-cancer-by-performing-a-network-meta-analysis-of-eight-randomized-controlled-trials
#1
Minyong Kang, Chang Wook Jeong, Cheol Kwak, Ja Hyeon Ku, Hyeon Hoe Kim
Various novel androgen receptor (AR) targeting drugs have been developed recently and have shown beneficial effects on survival in patients with metastatic castration-resistant prostate cancer (mCRPC). However, no consensus has been reached regarding which of these agents provides the most favorable oncological outcomes. Here, we aimed to compare the efficacy of novel AR-targeted agents by performing a network meta-analysis of randomized controlled trials (RCTs). We included eight RCTs for men with mCRPC treated with one of the AR targeting agents: abiraterone acetate, enzalutamide, or orteronel...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28545997/factors-associated-with-survival-following-radium-223-treatment-for-metastatic-castration-resistant-prostate-cancer
#2
William W Wong, Eric M Anderson, Homan Mohammadi, Thomas B Daniels, Steve E Schild, Sameer R Keole, C Richard Choo, Katherine S Tzou, Alan H Bryce, Thai H Ho, Fernando J Quevedo, Sujay A Vora
BACKGROUND: Radium-223 ((223)Ra) improves survival in patients with metastatic castration-resistant prostate cancer (mCRPC). This retrospective analysis was performed to better understand its efficacy in routine clinical practice and identify factors associated with survival. MATERIALS AND METHODS: Sixty-four patients with mCRPC who received (223)Ra between 2013 and 2015 were the basis of this retrospective study. Clinical outcomes and patient characteristics were obtained...
April 26, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28545929/a-simple-hplc-uv-method-for-quantification-of-enzalutamide-and-its-active-metabolite-n-desmethyl-enzalutamide-in-patients-with-metastatic-castration-resistant-prostate-cancer
#3
Alicja Puszkiel, Alain Plé, Olivier Huillard, Gaëlle Noé, Constance Thibault, Stéphane Oudard, François Goldwasser, Michel Vidal, Jérome Alexandre, Benoit Blanchet
Enzalutamide is currently approved for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). To date, a single liquid chromatographic-tandem mass spectroscopy method is available to measure plasma enzalutamide concentrations in mCRPC patients. In this work, an accurate and sensitive HPLC-UV method has been developed for the simultaneous determination of enzalutamide and its active metabolite, N-desmethyl enzalutamide in plasma from mCRPC patients. Before precipitation of proteins with acetonitrile, samples were spiked with nilutamide (internal standard)...
April 5, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28532278/tackling-non-metastatic-castration-resistant-prostate-cancer-special-considerations-in-treatment
#4
Archana Anantharaman, Eric J Small
Prostate cancer (PCa) is currently the second most common cancer affecting men worldwide. Metastatic castration-resistant prostate cancer (mCRPC) is the incurable form of PCa, carrying the poorest prognosis, and can develop from non-metastatic CRPC (M0 CRPC). CRPC is defined as progression of the disease with castrate level testosterone levels, achieved with primary androgen deprivation therapy (ADT). M0 CRPC is a highly heterogeneous disease process lacking clear standard of care therapies. Areas covered: In this review, a broad literature search was undertaken to explore data available for therapeutic options and guidelines in the management of M0 CRPC...
May 23, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28529549/abiraterone-acetate-and-prednisone-in-chemotherapy-na%C3%A3-ve-prostate-cancer-patients-rationale-evidence-and-clinical-utility
#5
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
#6
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/28488360/cabazitaxel-in-patients-with-metastatic-castration-resistant-prostate-cancer-safety-and-quality-of-life-data-from-the-australian-early-access-program
#7
Phillip Parente, Siobhan Ng, Francis Parnis, Alex Guminski, Howard Gurney
AIM: Cabazitaxel is a next generation taxane that has been shown to improve overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC) whose disease progressed during or after docetaxel-based therapy. A worldwide early access program (EAP) study was established to provide access to cabazitaxel ahead of commercial availability and to evaluate its safety and tolerability. The Australian EAP included patient-reported outcomes to evaluate the impact of cabazitaxel on quality of life (QoL)...
May 10, 2017: Asia-Pacific Journal of Clinical Oncology
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
#8
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/28473655/lipid-catabolism-inhibition-sensitizes-prostate-cancer-cells-to-antiandrogen-blockade
#9
Thomas W Flaig, Maren Salzmann-Sullivan, Lih-Jen Su, Zhiyong Zhang, Molishree Joshi, Miguel A Gijón, Jihye Kim, John J Arcaroli, Adrie Van Bokhoven, M Scott Lucia, Francisco G La Rosa, Isabel R Schlaepfer
Prostate cancer (PCa) is the most common malignancy among Western men and the second leading-cause of cancer related deaths. For men who develop metastatic castration resistant PCa (mCRPC), survival is limited, making the identification of novel therapies for mCRPC critical. We have found that deficient lipid oxidation via carnitine palmitoyltransferase (CPT1) results in decreased growth and invasion, underscoring the role of lipid oxidation to fuel PCa growth. Using immunohistochemistry we have found that the CPT1A isoform is abundant in PCa compared to benign tissue (n=39, p<0...
April 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28449621/emerging-role-of-radium-223-in-the-growing-therapeutic-armamentarium-of-metastatic-castration-resistant-prostate-cancer
#10
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...
June 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28440324/lutetium-177-labelled-anti-prostate-specific-membrane-antigen-antibody-and-ligands-for-the-treatment-of-metastatic-castrate-resistant-prostate-cancer-a-systematic-review-and-meta-analysis
#11
R J S Calopedos, V Chalasani, R Asher, L Emmett, H H Woo
BACKGROUND: Promising therapeutic results of the prostate-specific membrane antigen (PSMA) ligand have been shown when labelling with lutetium-177 ((177)Lu). We performed a systematic review and meta-analysis to assess the therapeutic response of (177)Lu-PSMA in the treatment of metastatic castration-resistant prostate cancer (mCRPC). METHODS: A systematic review was conducted using electronic databases up to December 2016. Two reviewers independently extracted data and assessed methodological quality...
April 25, 2017: Prostate Cancer and Prostatic Diseases
https://www.readbyqxmd.com/read/28440320/a-review-of-pomegranate-in-prostate-cancer
#12
REVIEW
C J Paller, A Pantuck, M A Carducci
BACKGROUND: Preclinical studies showing that pomegranate juice and its components inhibit prostate cancer led to multiple clinical trials to determine whether pomegranate products could slow the growth of prostate cancer. This review summarizes the preclinical data and discusses the results of the clinical trials. METHODS: Trials targeted patients on active surveillance, neoadjuvant patients, patients with biochemical recurrence (BCR) following local therapy for prostate cancer, and patients with metastatic castration-resistant prostate cancer (mCRPC)...
April 25, 2017: Prostate Cancer and Prostatic Diseases
https://www.readbyqxmd.com/read/28428880/long-term-complete-remission-with-ipilimumab-in-metastatic-castrate-resistant-prostate-cancer-case-report-of-two-patients
#13
Luc Cabel, Elika Loir, Gwenaelle Gravis, Pernelle Lavaud, Christophe Massard, Laurence Albiges, Giulia Baciarello, Yohann Loriot, Karim Fizazi
BACKGROUND: Prostate cancer is one of the most common cancers in men and the fourth leading cause of cancer mortality worldwide. Although major progress has been achieved in the last years for patients with metastatic castrate-resistant prostate cancer (mCRPC), thanks to next-generation androgen receptor axis targeted drugs, taxanes, and bone-targeted agents, immunotherapy has not been widely approved and used for the treatment of prostate cancer. Two large studies with ipilimumab, an anti-CTLA-4 (cytotoxic T-lymphocyte antigen 4) antibody reported improved progression-free survival, but not statistically improved overall survival at the primary analysis (CA184 043 and CA184 095)...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28427521/management-of-metastatic-castration-resistant-prostate-cancer-a-focus-on-radium-223-opinions-and-suggestions-from-an-expert-multidisciplinary-panel
#14
REVIEW
Sergio Baldari, Giuseppe Boni, Roberto Bortolus, Orazio Caffo, Giario Conti, Giuseppe De Vincentis, Fabio Monari, Giuseppe Procopio, Daniele Santini, Ettore Seregni, Riccardo Valdagni
Radium-223, a calcium mimetic bone-seeking radionuclide that selectively targets bone metastases with alpha particles, is approved for the treatment of men with metastatic castration-resistant prostate cancer (mCRPC) and symptomatic bone metastases. In patients with mCRPC, treatment with radium-223 has been associated with survival benefit, regardless of prior docetaxel use, and also has a positive impact on symptomatic skeletal events and quality of life. Radium-223 is best suited for patients with symptomatic mCRPC and bone-predominant disease and no visceral metastases, and may lead to better outcomes when given early in the course of the disease...
May 2017: Critical Reviews in Oncology/hematology
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
#15
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/28415742/androgen-receptor-amplification-is-concordant-between-circulating-tumor-cells-and-biopsies-from-men-undergoing-treatment-for-metastatic-castration-resistant-prostate-cancer
#16
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)...
March 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28408529/targeted-alpha-therapy-of-mcrpc-with-225-actinium-psma-617-dosimetry-estimate-and-empirical-dose-finding
#17
Clemens Kratochwil, Frank Bruchertseifer, Hendrik Rathke, Marcus Bronzel, Christos Apostolidis, Wilko Weichert, Uwe Haberkorn, Frederick Lars Giesel, Alfred Morgenstern
To develop a treatment protocol for (225)Ac-PSMA-617 alpha-radiation therapy in advanced stage, metastatic castration-resistant prostate cancer patients with PSMA-positive tumor phenotype. Methods: A dosimetry estimate was calculated based on time-activity-curves derived from serially performed (177)Lu-PSMA-617 scans extrapolated to the physical half-life of (225)Ac, assuming instant decay of instable daughter nuclides. Salvage therapies empirically conducted with 50kBq/kg (n = 4), 100kBq/kg (n = 4), 150kBq/kg (n = 2), 200kBq/kg (n = 4) (225)Ac-PSMA-617 were evaluated retrospectively regarding toxicity and treatment response...
April 13, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
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
#18
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
https://www.readbyqxmd.com/read/28395931/impact-of-abiraterone-acetate-and-enzalutamide-on-symptom-burden-of-patients-with-chemotherapy-naive-metastatic-castration-resistant-prostate-cancer
#19
S Salem, M Komisarenko, N Timilshina, L Martin, R Grewal, S Alibhai, A Finelli
AIMS: Treatments and disease burden of metastatic castration-resistant prostate cancer (mCRPC) considerably affect a patient's quality of life. However, patient-reported symptom burden data are still largely insufficient. This study sought to compare the self-reported symptom burden of men with chemotherapy-naive (CN) mCRPC treated with abiraterone acetate (AA) or enzalutamide (EZ) in routine clinical practice. MATERIALS AND METHODS: Between 2011 and 2015, 189 CN-mCRPC patients who had received AA (n = 76) or EZ (n = 113) at the Princess Margaret Cancer Centre were included...
April 8, 2017: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/28392429/-management-of-a-progressing-prostate-cancer-results-of-a-national-study
#20
F Rozet, M Roupret, C Hennequin, C Massard, P Blanchard, S Le Moulec
INTRODUCTION: The introduction of new treatments in metastatic castration resistant prostate cancer (mCRPC) requires a close follow-up to detect a progression and then to adapt the treatment. In that context, a national survey was proposed to a group of experts and the aim was to identify the modalities of surveillance in different clinical situations. METHODS: A questionnaire was sent to 1464 urologists, medical oncologists and radiotherapists, about a clinical case; it was about a patient presenting a prostate cancer, evolving from a biologic progression after radical prostatectomy to a situation of metastasis resistant to the castration...
May 2017: Progrès en Urologie
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