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radium-223 post docetaxel

Tomasz M Beer
Metastatic castration-resistant prostate cancer that is progressing despite docetaxel chemotherapy is difficult to treat and often aggressive. If not previously used, modern androgen signaling inhibitors have established clinical activity in this setting. Cabazitaxel and radium-223 have also been shown to extend survival in appropriately selected patients. Carboplatin-containing chemotherapy regimens have not been studied in randomized trials with a survival endpoint, but they have demonstrated activity in phase II trials and are occasionally considered in the post-docetaxel setting...
August 15, 2017: Oncology (Williston Park, NY)
Jan Norum, Carsten Nieder
BACKGROUND: Prostate cancer (PC) is the most common cancer in Western countries. More than one third of PC patients develop metastatic disease, and the 5-year expected survival in distant disease is about 35%. During the last few years, new treatments have been launched for metastatic castrate-resistant prostate cancer (mCRPC). OBJECTIVES: We aimed to review the current literature on health economic analysis on the treatment of metastatic prostate cancer (mPC), compare the studies, summarize the findings and make the results available to administrators and decision makers...
December 2017: PharmacoEconomics
M Unda-Urzaiz, R Sousa-Campo, A Rodríguez-Antolín, C Silva-Marins, A Juárez-Soto, B Miñana-López, A Figueiredo-de Castro, J M Cozar-Olmos
CONTEXT: Radium-223 is an □ -particle transmitter with specific action on bone metastases. The Alpharadin in Symptomatic Prostate Cancer Patients (ALSYMPCA) study showed that radium-223 extended overall survival and delayed the onset of bone events in patients with symptomatic castration-resistant prostate cancer with bone metastases (mCRPC) and without visceral metastases, with a good safety profile. OBJECTIVE: To review the new scientific evidence on radium-223 based on prespecified and post-hoc analyses of the ALSYMPCA study and on early-access programs after the publication of the ALSYMPCA study, thereby providing new data on the management of patients with mCRPC...
July 12, 2017: Actas Urologicas Españolas
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
D Keizman, M O Fosboel, H Reichegger, A Peer, E Rosenbaum, M-C Desax, V Neiman, P M Petersen, J Mueller, R Cathomas, M Gottfried, H Dresler, D Sarid, W Mermershtain, K Rouvinov, J Mortensen, S Gillessen, G Daugaard, A Omlin
BACKGROUND: The imaging response to radium-223 therapy is at present poorly described. We aimed to describe the imaging response to radium-223 treatment. METHODS: We retrospectively evaluated the computed tomography (CT) and bone scintigraphy response of metastatic castration-resistant prostate cancer (CRPC) patients treated with radium-223, in eight centers in three countries. RESULTS: A total of 130 patients were included, the majority (n=84, 65%) received radium-223 post docetaxel...
February 28, 2017: Prostate Cancer and Prostatic Diseases
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
Benjamin Kearns, Abdullah Pandor, Matt Stevenson, Jean Hamilton, Duncan Chambers, Mark Clowes, John Graham, M Satish Kumar
As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the company that manufactures cabazitaxel (Jevtana(®), Sanofi, UK) to submit evidence for the clinical and cost effectiveness of cabazitaxel for treatment of patients with metastatic hormone-relapsed prostate cancer (mHRPC) previously treated with a docetaxel-containing regimen. The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG)...
April 2017: PharmacoEconomics
Chad R Ritch, Michael S Cookson
Docetaxel based chemotherapy showed survival benefit and emerged as the mainstay of treatment for castration resistant prostate cancer (CRPC) in 2004. However, therapeutic options have expanded rapidly since 2011. The spectrum of new agents is broad and includes drugs that target the androgen axis (enzalutamide, abiraterone), immunotherapy (sipuleucel-T), bone seeking radionuclides (radium-223), and second line chemotherapy (cabazitaxel). In addition, new agents have been developed to reduce skeletal related events (denosumab)...
October 17, 2016: BMJ: British Medical Journal
Nicholas J Vogelzang, Robert E Coleman, Jeff M Michalski, Sten Nilsson, Joe M O'Sullivan, Christopher Parker, Anders Widmark, Marcus Thuresson, Lei Xu, Joseph Germino, Oliver Sartor
BACKGROUND: Myelosuppression is common in patients with progressive castration-resistant prostate cancer and bone metastases. Radium-223 prolongs overall survival in these patients but may cause myelosuppression; understanding risk factors will improve clinical decision making. We describe hematologic safety of radium-223 in ALSYMPCA and post hoc analyses identifying patients at increased risk for hematologic toxicity. PATIENTS AND METHODS: Hematologic parameters and adverse events were analyzed...
February 2017: Clinical Genitourinary Cancer
S Nilsson, P Cislo, O Sartor, N J Vogelzang, R E Coleman, J M O'Sullivan, J Reuning-Scherer, M Shan, L Zhan, C Parker
BACKGROUND: Radium-223 dichloride (radium-223), a first-in-class α-emitting radiopharmaceutical, is recommended in both pre- and post-docetaxel settings in patients with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases based on overall survival benefit demonstrated in the phase III ALSYMPCA study. ALSYMPCA included prospective measurements of health-related quality of life (QOL) using two validated instruments: the general EuroQoL 5D (EQ-5D) and the disease-specific Functional Assessment of Cancer Therapy-Prostate (FACT-P)...
May 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Benjamin A Gartrell, Fred Saad
The treatment armamentarium for metastatic castration-resistant prostate cancer (mCRPC) has increased significantly over the past several years. Approved drugs associated with improved survival include androgen pathway-targeted agents (abiraterone acetate and enzalutamide), chemotherapeutics (docetaxel and cabazitaxel), an autologous vaccine (sipuleucel-T) and a radiopharmaceutical (radium-223). Abiraterone acetate, a prodrug of abiraterone, inhibits the CYP17A enzyme, a critical enzyme in androgen biosynthesis...
August 2015: Therapeutic Advances in Urology
Sten Nilsson
INTRODUCTION: Approximately 10 - 20% of prostate cancer cases ultimately progress to castration-resistant prostate cancer (CRPC), for which there is a poor prognosis and a therapeutic need. Radium-223 dichloride (radium-223 [Xofigo]) is a first-in-class α-emitting radiopharmaceutical shown to significantly prolong overall survival in patients with CRPC with symptomatic bone metastases and no visceral metastases. Current treatment guidelines recommended it in both pre- and post-docetaxel settings...
July 2015: Expert Opinion on Drug Safety
Tian Zhang, Jason Zhu, Daniel J George, Andrew J Armstrong
INTRODUCTION: Over the past decade, treatment options for men with metastatic castration-resistant prostate cancer (CRPC) have expanded with the addition of abiraterone acetate (AA), enzalutamide, sipuleucel-T, radium-223, docetaxel and cabazitaxel. The optimal sequencing of therapies in the context of efficacy and known cross-resistance remains uncertain. AREAS COVERED: We review the development of enzalutamide (MDV3100, Xtandi), a novel second-generation androgen receptor (AR), and AA (Zytiga), a selective, irreversible inhibitor of cytochrome P17...
March 2015: Expert Opinion on Pharmacotherapy
Hsin-Ho Liu, Yuh-Shyan Tsai, Chen-Li Lai, Chih-Hsin Tang, Chih-Ho Lai, Hsi-Chin Wu, Jer-Tsong Hsieh, Che-Rei Yang
With advances in molecular biologic and genomic technology, detailed molecular mechanisms for development of castration-resistant prostate cancer (CRPC) have surfaced. Metastatic prostate cancer (PCa) no longer represents an end stage, with many emerging therapeutic agents approved as effective in prolonging survival of patients from either pre- or post-docetaxel stage. Given tumor heterogeneity in patients, a one-size-fits-all theory for curative therapy remains questionable. With the support of evidence from continuing clinical trials, each treatment modality has gradually been found suitable for selective best-fit patients: e...
2014: BioMedicine
J Cassinello, M A Climent, A González del Alba, B Mellado, J A Virizuela
Androgen deprivation treatment is the current standard first-line treatment for metastatic prostate cancer. For several years, docetaxel was the only treatment with a proven survival benefit for castration-resistant prostate cancer (CRPC). Since docetaxel became standard of care for men with symptomatic metastatic castration-resistant prostate cancer (CRPC), three treatment virtual spaces, for treatment and drug development in CPRC, have emerged: pre-docetaxel, docetaxel combinations and post-docetaxel. Sipuleucel-T, cabazitaxel, abiraterone, enzalutamide and radium-223 have been approved in the pre- or post-docetaxel setting in metastatic CRPC during the last few years...
December 2014: Clinical & Translational Oncology
Oliver Sartor, Silke Gillessen
Six different treatments have demonstrated improved survival in phase III trials targeted to patients with metastatic castration-resistant prostate cancer (mCRPC). Front-line therapeutic options for mCRPC include docetaxel, sipuleucel-T, abiraterone and radium-223. Post-docetaxel options include cabazitaxel, abiraterone, enzalutamide and radium-223. Despite much progress in recent years, much is yet unknown and debates occur over optimal treatment choices and sequences. None of the new agents have been compared to one another, thus physicians in practice today must make choices based on non-randomized comparisons, toxicity considerations and various assumptions...
May 2014: Asian Journal of Andrology
Michael Hurwitz, Daniel P Petrylak
Ten years ago, the clinician treating metastatic castration-resistant prostate cancer (CRPC) had palliative options for treatment of symptomatic patients, such as the combination of mitoxantrone combined with prednisone, as well as isotope therapy. In 2004, docetaxel-based chemotherapy regimens were shown to provide an overall survival benefit for patients with CRPC. Today, the prostate cancer oncologist is in the enviable position of having six U.S. Food and Drug Administration-approved agents to choose from: immunotherapy (sipuleucel-T), hormonal therapies (abiraterone, enzalutamide), radiopharmaceuticals (radium-223), and chemotherapy (docetaxel, cabazitaxel), in addition to agents being administered in clinical trials...
November 2013: Oncology (Williston Park, NY)
Aurelius Omlin, Carmel Pezaro, Silke Gillessen Sommer
In the last three years, five novel treatments have been shown to improve survival in metastatic castration-resistant prostate cancer (CRPC). These novel treatments have distinct mechanisms of action: tubulin-binding chemotherapy (cabazitaxel); immunotherapy (sipuleucel-T); CYP-17 inhibition (abiraterone); androgen receptor (AR) blockade (enzalutamide); and radioisotope therapy (radium-223). For a number of years, docetaxel was the only treatment with a proven survival benefit for patients with CRPC. Therefore, somewhat artificially, three treatment spaces for drug development in CRPC have emerged: pre-docetaxel; docetaxel combinations; and post-docetaxel...
February 2014: Therapeutic Advances in Urology
Deborah Mukherji, Aurelius Omlin, Carmel Pezaro, Ali Shamseddine, Johann de Bono
With five novel therapies shown to improve survival in metastatic castration-resistant prostate cancer (CRPC) in the last 3 years, patients are now living longer and experiencing better quality of life. Since docetaxel became standard of care for men with symptomatic metastatic CRPC, three artificial treatment "spaces" have emerged for prostate cancer drug development: pre-docetaxel, docetaxel combinations, and following docetaxel. Multiple therapies are currently under development in both early and late stage CRPC...
September 2014: Cancer Metastasis Reviews
D Lorente, J S De Bono
Prostate cancer is the most common malignancy in Western Europe, of which approximately 10-20% presents with advanced or metastatic disease. Initial response with androgen deprivation therapy is almost universal, but progression to castration resistant prostate cancer (CRPC), an incurable disease, occurs in approximately 2-3 years. In recent years, the novel taxane cabazitaxel, the hormonal agents abiraterone and enzalutamide, the immunotherapeutic agent sipuleucel-T and the radiopharmaceutical radium-223 have been shown to prolong survival in large randomised trials, thus widely increasing the therapeutic armamentarium against the disease...
March 2014: European Journal of Cancer
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