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https://www.readbyqxmd.com/read/28096932/contemporary-agents-in-the-management-of-metastatic-castration-resistant-prostate-cancer
#1
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
#2
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/28063195/first-line-non-cytotoxic-therapy-in-chemotherapy-naive-patients-with-metastatic-castration-resistant-prostate-cancer-a-systematic-review-of-ten-randomised-clinical-trials
#3
REVIEW
Michiel H F Poorthuis, Robin W M Vernooij, R Jeroen A van Moorselaar, Theo M de Reijke
OBJECTIVE: To systematically evaluate all available treatment options in chemotherapy-naive patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: We systematically searched PubMed, EMBASE, and the Cochrane libraries up to March 1, 2016 for peer-reviewed publications on randomised clinical trials (RCTs). RCTs were included if progression-free survival (PFS), overall survival (OS), quality of life (QoL), or adverse events (AEs) were quantitatively evaluated...
January 6, 2017: BJU International
https://www.readbyqxmd.com/read/28058455/-bone-specific-therapy-with-radium-223-dichloride-castration-resistant-prostate-cancer-with-symptomatic-bone-metastases
#4
R Tauber, J Gschwend, K Scheidhauer, M Eiber, M Krönke
Radium-223 dichloride (Xofigo®, Alpharadin) is approved for the treatment of metastatic castration-resistant prostate cancer with symptomatic bone metastases and no known visceral metastases. As a calcium mimetic, it is integrated into osteoplastic bone lesions and emits alpha particles with high energy which leads to local destruction of tumor cells. In the 2013 published ALSYMPCA trial, a significant advantage for overall survival and quality of life in comparison to placebo was found. Recent data suggest an increased potential in combination with next generation hormonal treatment...
January 2017: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/28048765/su-f-t-57-delivered-activity-accuracy-of-radium-223-dichloride-injections-when-being-administrated-for-castration-resistant-prostate-cancer-symptomatic-bone-metastases-the-impact-of-residual-activity-in-the-spent-syringe-and-dispensing-accuracy-of-ra-223
#5
G Jennings
PURPOSE: To quantify the delivered activity accuracy of Radium 223 dichloride injections, when being administrated for castration - resistant prostate cancer, symptomatic bone metastases. The impact of residual activity in the spent syringe and dispensing accuracy of Ra 223. METHODS: The administration is by slow intravenous injection over 1 minute followed by double flushing of the 10 mL syringe and IV with saline. Eighty (80) procedures was used to investigate variations in the activity from the amount prescribed (µCi) = 1...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28034291/radiopharmaceuticals-for-diagnosis-and-therapy-of-neuroendocrine-differentiated-prostate-cancer
#6
Giampiero Giovacchini, Elisabetta Giovannini, Mattia Riondato, Andrea Ciarmiello
Neuroendocrine differentiation of prostate cancer (PCa) is a relatively frequent event, generally understudied, that carries important prognostic information. It is most frequently observed during the advanced stages of disease, when PCa has lost its sensitivity to androgen deprivation therapy or to chemotherapy, moderate to diffuse bone metastatic spread dominates the imaging scenario and it is responsible for painful clinical symptomatology. However, evidences indicate that neuroendocrine differentiation is a progressive phenomenon that starts at the very early part of the pathogenesis of cancer transformation contributing to it...
December 29, 2016: Current Radiopharmaceuticals
https://www.readbyqxmd.com/read/27990667/clinical-correlates-of-benefit-from-radium-223-therapy-in-metastatic-castration-resistant-prostate-cancer
#7
Ajjai Alva, Luke Nordquist, Stephanie Daignault, Saby George, Jorge Ramos, Costantine Albany, Sudhir Isharwal, Matthew McDonald, Gregory Campbell, Pongwut Danchaivijitr, Sarah Yentz, Aseem Anand, Evan Y Yu
BACKGROUND: We sought to identify potential clinical variables associated with outcomes after radium-223 therapy in routine practice. METHODS: Consecutive non-trial mCRPC patients who received ≥1 dose of radium dichloride-223 at four academic and one community urology-specific cancer centers from May 2013 to June 2014 were retrospectively identified. Association of baseline and on-therapy clinical variables with number of radium doses received and clinical outcomes including overall survival were analyzed using chi-square statistics, cox proportional hazards, and Kaplan-Meier methods...
December 19, 2016: Prostate
https://www.readbyqxmd.com/read/27930924/effect-of-radium-223-dichloride-ra-223-on-hospitalisation-an-analysis-from-the-phase-3-randomised-alpharadin-in-symptomatic-prostate-cancer-patients-alsympca-trial
#8
Christopher Parker, Lin Zhan, Paul Cislo, Jonathan Reuning-Scherer, Nicholas J Vogelzang, Sten Nilsson, Oliver Sartor, Joe M O'Sullivan, Robert E Coleman
Symptomatic skeletal events (SSEs) commonly occur in patients with bone metastases, often leading to hospitalisations and decreased quality-of-life. In the ALSYMPCA trial, radium-223 significantly improved overall survival (hazard ratio 0.70, 95% confidence interval [CI] 0.58-0.83, P < 0.001) and prolonged time to first SSE (hazard ratio 0.66, 95% CI 0.52-0.83, P = 0.00037) and subsequent SSE (hazard ratio 0.65, 95% CI 0.51-0.83, P = 0.00039) versus placebo in patients with castration-resistant prostate cancer with symptomatic bone metastases and no known visceral metastases...
January 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/27911459/evaluation-of-bone-metastases-by-18f-choline-pet-ct-in-a-patient-with-castration-resistant-prostate-cancer-treated-with-radium-223
#9
Piera Scalzi, Cinzia Baiocco, Sabrina Genovese, Antonella Trevisan, Zuzana Sirotova, Carlo Poti
BACKGROUND: To date, bone metastases remain the main cause of morbidity and mortality in patients with metastatic castration-resistant prostate cancer (mCRPC). Therefore, the combination of accurate early detection of bony disease and effective treatment of these lesions is crucial in the management of mCRPC patients, but clinical trials specifically designed to test novel approaches are currently lacking. CASE DESCRIPTION: This report describes the case of a 74-year-old male with bone mCRPC and symptomatic and biochemical progression, who underwent radium-223 therapy, following previous treatment failure...
December 2, 2016: Urologia
https://www.readbyqxmd.com/read/27893426/sublethal-exposure-to-alpha-radiation-223ra-dichloride-enhances-various-carcinomas-sensitivity-to-lysis-by-antigen-specific-cytotoxic-t-lymphocytes-through-calreticulin-mediated-immunogenic-modulation
#10
Anthony S Malamas, Sofia R Gameiro, Karin M Knudson, James W Hodge
Radium-223 dichloride (Xofigo®; 223Ra) is an alpha-emitting radiopharmaceutical FDA-approved for the treatment of bone metastases in patients with advanced castration-resistant prostate cancer. It is also being examined clinically in patients with breast and lung carcinoma and patients with multiple myeloma. As with other forms of radiation, the aim of 223Ra is to reduce tumor burden by directly killing tumor cells. External beam (photon) and proton radiation have been shown to augment tumor sensitivity to antigen-specific CD8+ cytotoxic T lymphocytes (CTLs)...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27885457/-psma-targeted-radioligand-therapy-in-prostate-cancer
#11
M M Heck, M Retz, R Tauber, K Knorr, C Kratochwil, M Eiber
Radioligand therapy (RLT) directed against prostate-specific membrane antigen (PSMA) enables tumor-specific treatment directed against PSMA-overexpressing prostate cancer cells. Several PSMA ligands such as PSMA-617 or PSMA-I&T have been developed that can be labeled with β‑radiating lutetium-177. These are currently applied in compassionate use programs to treat metastatic castration-resistant prostate cancer (mCRPC). PSMA-directed RLT is currently being offered in several nuclear medicine departments throughout Germany...
January 2017: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/27876504/disease-and-treatment-characteristics-of-men-diagnosed-with-metastatic-hormone-sensitive-prostate-cancer-in-real-life-analysis-from-a-commercial-claims-database
#12
Thomas W Flaig, Ravi C Potluri, Yvette Ng, Mary B Todd, Maneesha Mehra, Celestia S Higano
BACKGROUND: Our understanding of the clinical characteristics and treatment patterns of men who present with newly diagnosed metastatic (M1) hormone-sensitive prostate cancer is based mainly on clinical trial data. We sought to characterize the M1 population seen in routine clinical practice using a commercial claims database. PATIENTS AND METHODS: A US claims (2000-2013) database was used to identify patients with an index diagnosis of prostate cancer. M1 patients were identified by "International Classification of Diseases, 9th revision, Clinical Modification" diagnosis codes of metastasis to bone, viscera, distant lymph node, and unspecified sites within 90 days of the prostate cancer diagnosis...
October 18, 2016: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/27843540/radium-223-and-metastatic-castration-resistant-prostate-cancer-all-that-glitters-is-not-gold
#13
REVIEW
Carlo Aprile, Marco G Persico, Lorenzo Lodola, Federica E Buroni
After being approved by the National Drug Agency in several countries, Radium-223 (Ra-223) is gaining wide acceptance in the treatment of bone metastatic castration resistant prostate cancer. The exact mechanism of action remain unclear: The established model of direct alpha-particle irradiation from the remodelling bone surface, where Ra-223 accumulates, surrounding the tumor foci can explain a lethal effect only on metastatic microdeposits, but not on higher tumor burden. According to the "pre-metastatic niche model", it is likely that Ra-223 targets several non-tumoral cell types of the tumor microenvironment involved in the complex mechanism of cancer bone homing and colonization...
October 28, 2016: World Journal of Radiology
https://www.readbyqxmd.com/read/27843209/radioisotopes-in-management-of-metastatic-prostate-cancer
#14
REVIEW
Amar Raval, Tu D Dan, Noelle L Williams, Andrew Pridjian, Robert B Den
INTRODUCTION: Metastatic prostate cancer continues to be a leading cause of morbidity and mortality in men with prostate cancer. Over the last decade, the treatment landscape for patients with castrate-resistant disease has drastically changed, with several novel agents demonstrating an improvement in overall survival in large, multi-institutional randomized trials. Traditional treatment with radioisotopes has largely been in the palliative setting. However, the first in class radiopharmaceutical radium-223 has emerged as the only bone-directed treatment option demonstrating an improvement in overall survival...
October 2016: Indian Journal of Urology: IJU: Journal of the Urological Society of India
https://www.readbyqxmd.com/read/27835737/a-radium-223-microgenerator-from-cyclotron-produced-trace-actinium-227
#15
Diane S Abou, Juile Pickett, John E Mattson, Daniel L J Thorek
The alpha particle emitter Radium-223 dichloride ((223)RaCl2) has recently been approved for treatment of late-stage bone metastatic prostate cancer. There is considerable interest in studying this new agent outside of the clinical setting, however the supply of (223)Ra is limited and expensive. We have engineered a (223)Ra microgenerator using traces of (227)Ac previously generated from cyclotron-produced (225)Ac. Radiochemically pure (223)RaCl2 was made, characterized, evaluated in vivo, and the source was recovered in high yield for regeneration of the microgenerator...
January 2017: Applied Radiation and Isotopes
https://www.readbyqxmd.com/read/27825434/radium-223-therapy-of-bone-metastases-in-prostate-cancer
#16
REVIEW
Sten Nilsson
Metastatic castration-resistant prostate cancer frequently metastasizes to the bone, often resulting in painful skeletal events, reduced quality of life, and reduced survival. Radium-223 is a first-in-class alpha-emitting radiopharmaceutical that has proven to prolong overall survival, delay time to symptomatic skeletal events, and improve quality of life in patients with castration-resistant prostate cancer and symptomatic bone metastases and no visceral metastases. Radium-223 provides survival benefit to patients with castration-resistant prostate cancer and symptomatic bone metastases, regardless of prior docetaxel use...
November 2016: Seminars in Nuclear Medicine
https://www.readbyqxmd.com/read/27822685/sequencing-treatment-for-castration-resistant-prostate-cancer
#17
REVIEW
Catherine E Handy, Emmanuel S Antonarakis
Prostate cancer is the most common non-cutaneous cancer diagnosed in men and the second leading cause of male cancer deaths in the USA. While most cases are diagnosed in early stages, some will present as or progress to metastatic disease and eventually castration-resistant prostate cancer (mCRPC) which has a mortality rate exceeding 50 %. There are currently six approved systemic life-prolonging therapies for use in mCRPC, yet little data to guide sequencing. Clinical factors, including the presence or absence of symptoms and the presence or absence of visceral metastases, should help determine the best therapeutic choice at each treatment node...
December 2016: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/27800631/meeting-report-from-the-prostate-cancer-foundation-scientific-working-group-on-radium-223
#18
REVIEW
Andrea K Miyahira, Michael Morris, Howard R Soule
INTRODUCTION: The Prostate Cancer Foundation (PCF) convened a Scientific Working Group Meeting on Radium-223 on September 8, 2016, at The Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan Kettering Cancer Center. METHODS: The meeting was attended by 18 investigators with expertise in radium-223, bone biology, molecular imaging, biomarkers, and prostate cancer clinical trials. The goal of this meeting was to discuss the known and unknown surroundings the therapeutic effects of the bone targeting agent radium-223, in bone metastatic prostate cancer therapy, and to outline the most critical studies needed to improve the clinical use of this agent...
November 1, 2016: Prostate
https://www.readbyqxmd.com/read/27796762/new-biomarkers-for-selecting-the-best-therapy-regimens-in-metastatic-castration-resistant-prostate-cancer
#19
Isabel Heidegger, Axel Heidenreich, David Pfister
Prostate cancer is the most common cancer in men. In recent years, several new targeted therapeutic agents for the treatment of metastatic castration resistant prostate cancer (mCRPC) have been developed. These include androgen receptor targeting agents, new taxanes, radium-223, and immunotherapies. In this short review, we provide a summary of clinical and preclinical biomarkers for each of these new treatment strategies, also including new markers currently presented in conference papers only. Moreover, we address the role of these biomarkers in clinical routine with the aim to select best-personalized treatment strategies for patients...
October 27, 2016: Targeted Oncology
https://www.readbyqxmd.com/read/27793893/radium-223-insight-and-perspectives-in-bone-metastatic-castration-resistant-prostate-cancer
#20
REVIEW
Federica Eleonora Buroni, Marco Giovanni Persico, Francesca Pasi, Lorenzo Lodola, Rosanna Nano, Carlo Aprile
(223)Ra prolongs overall survival in symptomatic patients affected by multiple bone-metastatic castration-resistant prostatic cancer, without visceral or nodal involvement. However, many questions remain about its mechanisms of action, and its use in clinical practice is still unresolved. First of all, what is the main target of alpha-particle emission, that is, in what way does it influences the tumor microenvironment? When is the best timing in the course of the disease, extending its use to asymptomatic low-volume or even to the micrometastatic phase? What are suitable biomarkers to be employed as prognostic factors and response indicators? Which associations with other drugs and their sequence can offer the best results, and is their effect additive or synergistic? Ultimately, in the current climate of spending review, what is the optimal cost and benefit ratio regarding available treatments? In this review, we tried to answer these questions by analyzing the available scientific literature...
2016: Anticancer Research
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