cabazitaxel and Bone-Neoplasms

Treatment options for metastatic castration-resistant prostate cancer (mCRPC) have expanded in recent years and include cytotoxic agents (e.g., docetaxel and cabazitaxel), immunotherapy (e.g., sipuleucel-T), oral hormonal therapies targeting the androgen receptor axis (e.g., enzalutamide and abiraterone), and targeted alpha therapy (e.g., radium-223 dichloride (radium-223)). Although treatment guidelines have been updated to reflect the availability of new agents, it is not easy to apply them in daily clinical practice because recommendations vary depending on patient comorbidities and disease characteristics. Furthermore, therapeutic accessibility, clinical judgment, and experience affect the selection of treatment options.. In this review, we provide practical guidance for the integration of radium-223 into the management of patients with mCRPC based on our collective clinical experience, as well as the available clinical trial data.. Radium-223 is a targeted alpha therapy; as a bone-seeking calcium mimetic, it accumulates in hydroxyapatite areas surrounding tumor lesions and selectively binds to the areas of increased bone turnover. Radium-223 prolongs overall survival and delays time to the first symptomatic skeletal events in men with mCRPC, and is indicated for the treatment of patients with CRPC, symptomatic bone metastases, and no known visceral metastases. We review its clinical efficacy and safety, practical guidance on identifying the appropriate patient, and recommendations for how best to educate and inform prospective patients regarding their treatment decision making. In addition, we review recent evidence for sequential and combination therapies with radium-223, provide our experiences with these treatment approaches, and discuss their implications for the future treatment of patients with mCRPC.. Based on our clinical experience, radium-223 should be considered relatively early in the treatment course in patients with mCRPC with bone metastases. Coordination of care among multidisciplinary team members, patients, and caregivers is essential for optimizing safe and effective treatment with all CRPC therapies.

Topics: Androstenes; Benzamides; Bone Neoplasms; Docetaxel; Humans; Male; Nitriles; Phenylthiohydantoin; Prostatic Neoplasms, Castration-Resistant; Radium; Receptors, Androgen; Taxoids; Treatment Outcome

Most men with advanced prostate cancer will develop bone metastases, which have a substantial impact on quality of life. Bone metastases can lead to skeletal-related events (SREs), which place a burden on patients and healthcare systems. For men with castration-resistant prostate cancer (CRPC) and bone metastases, the treatment landscape has evolved rapidly over the past few years. The relatively recent approvals of the hormonal agents abiraterone acetate and enzalutamide, second-line chemotherapy cabazitaxel, and the radiopharmaceutical radium-223 dichloride (radium-223), have provided clinicians with a greater choice of treatments. These compounds have benefits in terms of overall survival based on the results of pivotal phase 3 studies. The bisphosphonate zoledronic acid and the RANK ligand inhibitor denosumab are indicated for the prevention of SREs in men with metastatic CRPC but studies of these compounds have not demonstrated a survival benefit. The important question of the role of bisphosphonates or denosumab in combination with these new agents has thus materialised. Current and emerging evidence from clinical studies of abiraterone acetate, enzalutamide and radium-223, suggest that addition of bisphosphonates or denosumab to these new therapies may provide further clinical benefits for patients with prostate cancer and bone metastases. This evidence may help to shape clinical practice but are based largely on post hoc analyses of clinical trial data. It is therefore apparent that further data are required from both clinical studies and real-world settings to enable physicians to understand the efficacy and safety of combination therapy with the new agents plus bisphosphonates or denosumab.

Topics: Abiraterone Acetate; Benzamides; Bone Density Conservation Agents; Bone Neoplasms; Clinical Trials, Phase III as Topic; Denosumab; Diphosphonates; Humans; Imidazoles; Male; Nitriles; Phenylthiohydantoin; Prostatic Neoplasms, Castration-Resistant; Radioisotopes; Radium; Randomized Controlled Trials as Topic; Taxoids; Zoledronic Acid

When advanced prostate cancer recurred during hormonal therapy and became the castration-resistant prostate cancer, "vintage hormonal therapy," such as antiandrogen alternating therapy or estrogen-related hormonal therapy, was widely carried out in Japan until 2013. This vintage hormonal therapy controlled the progression of castration-resistant prostate cancer. When castration-resistant prostate cancer relapses during these therapies, chemotherapy using docetaxel has been carried out subsequently. Since new hormonal therapies using abiraterone acetate and enzalutamide, which improve the prognosis of castration-resistant prostate cancer, became available in Japan from 2014, therapeutic options for castration-resistant prostate cancer have increased. Furthermore, the improvement of the further prognosis is promising by using cabazitaxel for docetaxel-resistant castration-resistant prostate cancer and radium-223 for castration-resistant prostate cancer with bone metastasis. An increase in therapeutic options gives rise to many questions, including best timing to use them and the indication. Furthermore, physicians have to consider the treatment for the recurrence after having carried out chemotherapy. We want to argue the difference in hormonal therapy between Japan and Western countries, and problems when carrying out new treatments, and the importance of imaging in the present review article.

Topics: Abiraterone Acetate; Androgen Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Benzamides; Bone Neoplasms; Disease Progression; Docetaxel; Humans; Japan; Male; Neoplasm Recurrence, Local; Nitriles; Phenylthiohydantoin; Prognosis; Progression-Free Survival; Prostatic Neoplasms, Castration-Resistant; Radium; Taxoids

Incidence of bone metastases is very high in advanced prostate cancer patients. Bone metastases likely have a significant impact on functional status and quality of life, not only related to pain, but also to the relevant risk of skeletal-related events. A better understanding of mechanisms associated with bone metastatic disease secondary to prostate cancer and more specifically to the cross-talk between tumor cells and bone microenvironment in metastatic progression represented the background for the development of new effective bone-targeted therapies. Furthermore, a better knowledge of biological mechanisms driving disease progression led to significant advances in the treatment of castration-resistant prostate cancer, with the development and approval of new effective drugs. Aim of this review is to outline the physiopathology of bone metastases in prostate cancer and summarize the main results of clinical trials conducted with different drugs to control morbidity induced by skeletal metastases and bone disease progression. For each agent, therapeutic effect on bone metastases has been measured in terms of pain control and/or incidence of skeletal-related events, usually defined as a composite endpoint, including the need for local treatment (radiation therapy or surgery), spinal cord compression, pathological bone fractures. In details, data obtained with chemotherapy (mitoxantrone, docetaxel, cabazitaxel), new generation hormonal agents (abiraterone, enzalutamide), radium-223, bone-targeted agents (zoledronic acid, denosumab) and with several experimental agents (cabozantinib, dasatinib, anti-endothelin and other agents) in patients with castration-resistant prostate cancer are reviewed.

Topics: Androstenes; Anilides; Antineoplastic Agents; Benzamides; Bone Density Conservation Agents; Bone Neoplasms; Carcinoma; Dasatinib; Denosumab; Diphosphonates; Docetaxel; Humans; Imidazoles; Male; Mitoxantrone; Nitriles; Phenylthiohydantoin; Prostatic Neoplasms, Castration-Resistant; Pyridines; Radioisotopes; Radium; Taxoids; Zoledronic Acid

Despite castrate levels of androgens, the androgen receptor (AR) remains active and continues to drive prostate cancer progression. Since the approval of docetaxel, four additional agents that show a survival benefit have been registered on the basis of randomized phase 3 trials. These have included enzalutamide and abiraterone, two agents designed specifically to affect the androgen axis, sipuleucel-T, which stimulates the immune system and cabazitaxel, a chemotherapeutic agent. Denosumab was shown to significantly delay skeletal-related events. Clinicians are challenged with a multitude of treatment options and potential sequencing of these agents that, consequently, make clinical decision making more complex. The induction of constitutively-active AR splice variants (AR-Vs) driving clonal proliferation of AR-negative and AR-independent metastases may be one major potential mechanism of resistance to new hormone therapies.

Topics: Abiraterone Acetate; Androstenes; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Benzamides; Bone Neoplasms; Clinical Trials, Phase III as Topic; Denosumab; Docetaxel; Humans; Male; Nitriles; Phenylthiohydantoin; Prednisone; Prostatic Neoplasms, Castration-Resistant; Receptors, Androgen; Taxoids; Tissue Extracts

There has been dramatic improvement in the diagnosis and treatment of prostate cancer recently. The treatment of localized disease became more successful with the application of new, sophisticated techniques available for urologic surgeons and radiotherapists. Nevertheless a significant proportion of patients relapses after the initial local treatment or is diagnosed with metastatic disease at the beginning. In the past five years, six new drugs became registered for the treatment of metastatic, castration-resistant prostate cancer, such as sipuleucel-T, cabazitaxel, abiraterone, enzalutamide, the α-emitting radionuclide alpharadin and the receptor activator of nuclear factor kappa-B (RANK) ligand inhibitor denosumab. The availability of these new treatment options raises numerous questions. In this review we present the standard of care of metastatic prostate cancer by disease stage (hormone naive/ hormone sensitive metastatic prostate cancer, non-metastatic castration-resistant prostate cancer, oligometastatic/multimetastatic castration-resistant prostate cancer) and the emerging treatment modalities presently assessed in clinical trials. We would also like to give advice on debatable aspects of the management of metastatic prostate cancer.. A prosztatadaganat kezelésében az utóbbi évtized jelentõs fejlõdést eredményezett, javultak a daganat felismerésének lehetõségei azáltal, hogy pontosabb diagnosztikai módszerek állnak rendelkezésre. A nem metasztatikus daganat gyógyítási esélyei is javultak a fejlõdõ sugárterápia és az egyre hatékonyabb sebészi megoldások következtében. Ennek ellenére jelentõs azon betegek száma, akiknél a lokális ellátás ellenére progresszió alakul ki, vagy már a diagnózis felállításakor metasztatikus a betegség. A kasztrációrezisztens prosztatarák kezelésében az elmúlt öt év során 6 új hatóanyag került törzskönyvezésre. Ezek közül kettõ az androgén tengelyt célzó kezelések közé tartozik, a többi hatóanyag, illetve terápiás eljárás: immunterápia, kemoterápia, izotópkezelés és a RANK-ligand gátlása. Az új kezelések kapcsán számos kérdés merül fel. Közleményünk célja elõrehaladott prosztatadaganatban stádiumok (hormonnaiv/hormonérzékeny metasztatikus, kasztrációrezisztens nem metasztatikus, kasztrációrezisztens oligo- és multimetasztatikus) szerint a már egyértelmû evidenciák ismertetése, az új fejlesztések bemutatása, nyitott kérdések megvitatása.

Topics: Adrenal Cortex Hormones; Androgen Antagonists; Androstenes; Antineoplastic Agents, Hormonal; Benzamides; Bone Neoplasms; Denosumab; Drug Administration Schedule; Drug Approval; Gonadotropin-Releasing Hormone; Humans; Male; Nitriles; Phenylthiohydantoin; Prostatic Neoplasms; Taxoids; Tissue Extracts

Enzalutamide, abiraterone-acetate, and cabazitaxel are licensed post-docetaxel treatments of metastatic castration-resistant prostate cancer (mCRPC) in Hungary. The objectives of the study were to assess the efficacy and safety of post-docetaxel enzalutamide treatment and to compare it with abiraterone and with cabazitaxel, using Medline-based systematic literature search, and meta-analysis of randomised controlled trials (RCT). Overall 3 RCTs were included, one for each substance. Compared to placebo, enzalutamide proved significant efficacy in each primary and secondary endpoint. Enzalutamide extended median overall survival by 4.8 months. Due to lack of a common comparator in the cabazitaxel trial, only enzalutamide and abiraterone were involved in an indirect comparison. No significant difference was identified either in the primary endpoint (overall survival) (HR: 0.97, 95% CI: 0.75-1.25) or in frequencies of adverse events between these two treatments. However, enzalutamide was significantly more efficacious than abiraterone in 3 secondary endpoints: time to prostate-specific antigen (PSA) progression (HR: 0.43, 95% CI: 0.31-0.59), radiographic progression-free survival (HR: 0.6, 95% CI: 0.5-0.72), and PSA response rate (RR: 7.48, 95% CI: 2.83-19.72). Enzalutamide therapy proved clinical efficacy and safety in patients with post-docetaxel mCRPC. In the indirect comparison, efficacy and safety of abiraterone and enzalutamide were found to be similar.. Magyarországon jelenleg a metasztatikus, kasztrációrezisztens prosztatarák (mCRPC) terápiájában poszt-docetaxel alkalmazásban enzalutamid, abirateron és cabazitaxel hatóanyagok rendelhetõek. Célunk a Magyarországon 2013-ban törzskönyvezett enzalutamid klinikai hatásosságának és biztonságosságának elemzése és összehasonlítása abirateronnal és cabazitaxellel, szisztematikus irodalomkeresés és randomizált, kontrollált vizsgálatok (RCT) metaanalízissel végzett direkt és indirekt összehasonlítása módszerével. Mindhárom hatóanyag esetében 1-1 RCT került beválogatásra. A három hatóanyag minden elsõdleges és másodlagos végpontban szignifikánsan hatásosabbnak bizonyult a placebónál. Az enzalutamidkezelés a betegek medián túlélését 4,8 hónappal hosszabbította meg. Az indirekt összehasonlításba csak az enzalutamidot és az abirateront vontuk be, a cabazitaxel esetében nem volt közös komparátor. A két terápia között nem találtunk szignifikáns eltérést sem az elsõdleges végpontban (túlélés) (HR: 0,97, 95% KI: 0,75–1,25), sem a nemkívánatos események tekintetében. Három másodlagos végpontban az enzalutamid szignifikánsan hatásosabb az abirateronnál: prosztataspecifikus antigén (PSA) progresszióig eltelt idõ (HR: 0,43, 95% KI: 0,31–0,59), radiológiai progressziótól mentes túlélés (HR: 0,6, 95% KI: 0,5–0,72) és PSA-választ adók aránya (RR: 7,48, 95% KI: 2,83–19,72). Az enzalutamid klinikailag kedvezõ hatású és alkalmazása biztonságos poszt-docetaxel mCRPC kezelésében. Az indirekt összehasonlítás alapján az enzalutamid- és az abirateronkezelés klinikai hatásossága és biztonságossága hasonló.

Topics: Androstenes; Androstenols; Antineoplastic Agents; Benzamides; Bone Neoplasms; Humans; Male; Nitriles; Phenylthiohydantoin; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Randomized Controlled Trials as Topic; Taxoids; Treatment Outcome

Topics: Abiraterone Acetate; Androgen Antagonists; Androstadienes; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Denosumab; Docetaxel; Humans; Male; Neoplasms, Hormone-Dependent; Orchiectomy; Prostatic Neoplasms; Taxoids

Improved understanding of mechanisms underlying metastatic castration-resistant prostate cancer (mCRPC) progression has led to the recognition of multiple molecular targets and advances in the therapeutic landscape. The addition of abiraterone acetate, sipuleucel-T, cabazitaxel, and denosumab to the therapeutic armamentarium and the impending addition of MDV-3100 and radium-223 underscore the importance of androgen pathway inhibition, immunotherapy, tubulin antagonism, and pathophysiology of bone metastasis.. Review the next generation of molecular targets in mCRPC.. Medline databases were searched for >100 original articles published as of October 18, 2011, with the search terms metastatic castration-resistant prostate cancer, targeted therapy, biologic agents, and immunotherapy. Proceedings from the last 5 yr of conferences of the American Society of Clinical Oncology, American Urological Association, European Society of Medical Oncology, and the European Association of Urology were also searched. We included novel and promising drugs that have reached clinical trial evaluation.. The major findings were addressed in an evidence-based fashion. Prospective trials and important preclinical data were analyzed.. mCRPC is a disease with multiple molecular drivers. Molecular pathways being targeted in ongoing phase 3 trials are androgen signaling (MDV3100, TAK700), immunoregulatory pathways (ipilimumab, Prostvac-VF-TRICOM), Src (dasatinib), Met (cabozantinib), clusterin (custirsen), and angiogenesis (aflibercept, tasquinimod). The strides made in identifying multiple other novel molecular targets offer potential opportunities for further improving outcomes.

Topics: Abiraterone Acetate; Androstadienes; Anilides; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Benzamides; Bone Neoplasms; Cancer Vaccines; Carcinoma; Clinical Trials, Phase III as Topic; Clusterin; Dasatinib; Denosumab; Humans; Ipilimumab; Male; Nitriles; Orchiectomy; Phenylthiohydantoin; Prostatic Neoplasms; Pyridines; Pyrimidines; Quinolines; Quinolones; Radium; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Taxoids; Thiazoles; Tissue Extracts; Treatment Outcome; Vaccines, Synthetic

If androgen deprivation, chemical with LH-RH analogs or surgical with bilateral orchiectomy, still remains the stone edge of treatment of prostate cancer, in the metastatic setting, this hormonosensitivity, most of the time long, finally move on in hormonal-failure. If rare changes in the therapeutic strategy have been achieved in this setting since 2004 and the arrival of docetaxel, it is the global perception of the disease that has been modified and the definition of one specific entity: the castrate-resistant prostate cancer. This new definition and the changes of design and end-points of clinical trials testing new agents with strong recruitment during the past years have conducted to a real revolution in the management of castrate-refractory prostate cancer. The place of secondary hormonal manipulations, such as withdrawal of the anti-androgen, oestrogen or ketoconazole, still exists for a selected group of patients. In case of aggressive disease and symptoms, chemotherapy should be selected, docetaxel, in a three weeks schedule, and may be combined with Estracyt. It is time to consider the revolution of the post-chemotherapy setting with the arrival of two new drugs ; a cytotoxic one, the cabazitaxel and hormonal for the second one, the abiraterone acetate. The place of the immunotherapy with the sipuleucel-T may be more difficult to precise, especially in Europe, even if it has been finally indicated in the United States in the metastatic setting. Concerning bone metastasis, zoledronic acid was during a long time the only bone-targeted agent, effective in reducing the incidence of skeletal related events, and was recently exceeded by the denosumab, an anti-RANK ligand. Finally, let us hope that other changes will be achieved in the near future, with the cabazitaxel-docetaxel confrontation in the first-line setting, and the introduction of the abiraterone acetate before chemotherapy with docetaxel, already tested in ongoing trials.

Topics: Abiraterone Acetate; Androgen Antagonists; Androstadienes; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Bone Density Conservation Agents; Bone Neoplasms; Cancer Vaccines; Denosumab; Diphosphonates; Docetaxel; Estramustine; Humans; Imidazoles; Male; Orchiectomy; Prostatic Neoplasms; Taxoids; Tissue Extracts; Zoledronic Acid

The health-related quality-of-life (HRQOL) implications of advanced metastatic prostate cancer are variable. There are several different HRQOL instruments that measure domains germane to patients with advanced metastatic disease. The burden of prostate cancer is inversely related to the magnitude of HRQOL declines. Treatment with androgen deprivation therapy commonly results in HRQOL declines that have served as the impetus for intermittent therapy. Conversely, chemotherapeutic agents have been associated with improvements in functional status for men with castrate-resistant disease. Emerging therapies may result in significant HRQOL improvements in this population, and careful prospective evaluation of patient-reported outcomes will be required.

Topics: Androgen Antagonists; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Bone Neoplasms; Denosumab; Diphosphonates; Disease Progression; Docetaxel; Health Status Indicators; Humans; Imidazoles; Male; Mitoxantrone; Prostatic Neoplasms; Quality of Life; Taxoids; Treatment Outcome; Zoledronic Acid

Prostate cancer is the most common male cancer and one of the top causes of male cancer-related death in Western countries. Most patients with prostate cancer respond to initial androgen deprivation therapy but eventually progress to castration-resistant prostate cancer (CRPC). Although androgen receptor signaling remains the main driver in CRPC, a growing body of evidence suggests that other pathways are involved in this progression. This article reviews the preclinical data and current status of clinical trials therapeutically targeting tubulin, DNA repair, molecular chaperones such as CLU and Hsp27, tyrosine kinases, and DNA repair.

Topics: Bone Neoplasms; Cell Proliferation; Cell Survival; Dasatinib; Disease Progression; DNA Repair; Epothilones; Gene Fusion; Humans; Male; Neoplasm Invasiveness; Prostatic Neoplasms; Proto-Oncogene Proteins c-met; Pyrimidines; Receptors, Androgen; Taxoids; Thiazoles

Prostate cancer is the leading cause of cancer and second leading cause of death among men. Management of localized disease is fairly straight-forward, but treatment for locally advanced or metastatic disease is much less so. Androgen-deprivation therapy serves as the foundation of treatment for patients with locally advanced or metastatic disease. Although most patients with prostate cancer show a response to medical or surgical castration, many eventually experience a hormone-refractory, incurable state. Until recently, therapeutic options for CRPC have been limited and focused on systemic chemotherapeutic options. Unfortunately, however, this provides a minimal increase in overall survival, at the cost of significant additional toxicities. Therefore, much research has gone into developing other suitable therapies with potentially less toxicity. This article uses a case study approach to discuss new options for the treatment of castration-resistant prostate cancer.

Topics: Aged; Androgen Antagonists; Androgens; Androstenes; Androstenols; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Docetaxel; Humans; Immunotherapy; Male; Prostatectomy; Prostatic Neoplasms; Taxoids; Tissue Extracts; Treatment Outcome

Our understanding of - as well as our approach to - castration resistant prostate cancer is currently undergoing major changes. New drugs like the CYP-17 inhibitor abiraterone have shown that even in the "hormone refractory" stage the progression of prostate cancer is still driven by signaling of the androgen receptor. Changing the term to castration resistant prostate cancer is one consequence of these new insights. Here we give an overview on the current situation of drug development, therapeutic consequences and future trends.

Topics: Androgen Antagonists; Androstenes; Androstenols; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Bone Neoplasms; Cancer Vaccines; Clinical Trials as Topic; Docetaxel; Drug Resistance, Neoplasm; Humans; Ketoconazole; Male; Neoplasms, Hormone-Dependent; Orchiectomy; Prostate-Specific Antigen; Prostatic Neoplasms; Receptors, Androgen; Steroid 17-alpha-Hydroxylase; Taxoids; Tissue Extracts

To assess the efficacy of novel therapeutic agents, such as androgen receptor axis-targeted agents (ARATs) and cabazitaxel, for relapse of metastatic castration-resistant prostate cancer (mCRPC) after docetaxel in real-world practice, we performed a subanalysis using database from PROSTAT-BSI, a prospective observational study to evaluate the utility of software for quantifying bone metastases on bone scintigraphy.. Patients with clinically relapsed mCRPC after docetaxel treatment who received the new agents (NEW group) and those who did not (standard of care, SOC group) were included; patients who received ARAT before DOC treatment were excluded. Overall survival (OS) after docetaxel treatment was compared between the NEW and SOC groups.. Patients in the NEW group had significantly better OS from the start of docetaxel than those in the SOC group (the median OS in NEW and SOC was 28.9 months vs. 14.5 months, respectively). Furthermore, regardless of the time from androgen-deprivation therapy to the start of docetaxel at mCRPC, the NEW group had a better OS from relapse after docetaxel than the SOC group.. In clinical practice, OS of patients with relapse after docetaxel was significantly improved in the NEW group over the SOC group.

Topics: Aged; Aged, 80 and over; Androgen Receptor Antagonists; Antineoplastic Agents; Bone Neoplasms; Databases, Factual; Docetaxel; Humans; Japan; Male; Middle Aged; Prospective Studies; Prostatic Neoplasms, Castration-Resistant; Recurrence; Taxoids; Time Factors; Treatment Outcome

Treatment options for patients with unresectable and/or metastatic dedifferentiated liposarcoma (DDLPS) are limited. New drugs are required.. To assess whether cabazitaxel demonstrated sufficient antitumor activity in patients with metastatic or inoperable locally advanced DDLPS to justify further investigation in a phase 3 setting.. This international multicenter, open-label single-arm phase 2 trial was conducted at 10 institutions in 4 European countries from March 2015 to March 2019. Eligible patients had to have metastatic or locally advanced histologically proven DDLPS with evidence of disease progression within the past 6 months and had to have received no more than 1 previous line of chemotherapy.. After mandatory central review of tumor blocks, if the DDLPS diagnosis was confirmed, patients started treatment within 72 hours after registration. Cabazitaxel was administered at a dose of 25 mg/m2 IV infusion over 1 hour every 21 days until intolerance, progression, or withdrawal of consent.. The primary end point was progression-free survival (PFS) rate at 12 weeks per RECIST 1.1. Based on a Simon 2-stage design, at least 4 of 17 (stage 1) and 11 of 37 (stage 2) eligible and evaluable patients who were progression free at 12 weeks were needed. The final analysis report was completed on November 17, 2021.. Forty patients were registered, with 2 patients being ineligible. The number of cycles ranged from 1 to 30, with a median of 5; 26 patients (65%) received at least 4 cycles of cabazitaxel. Progression-free survival at 12 weeks was 55%, achieving the primary study end point. At a median follow-up of 21.6 months, median PFS was 6 months and median OS 21 months. Response rate (RR) was 8% with 1 clinical response (CR) and 2 partial responses (PR). Twenty-three (60.5%) patients had a stable disease (SD). Disease control (PR+SD) was achieved in 26 patients (68%).. This nonrandomized phase 2 clinical trial met its primary end point, with 21 of 38 patients (55%) being progression free at 12 weeks. These results suggest important activity of cabazitaxel in patients with metastatic or inoperable locally advanced DDLPS. The drug is worth being further studied in these tumors in a phase 3 setting.

Topics: Bone Neoplasms; Disease-Free Survival; Humans; Liposarcoma; Osteosarcoma; Sarcoma; Soft Tissue Neoplasms

Topics: Abiraterone Acetate; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Benzamides; Bone Neoplasms; Combined Modality Therapy; Docetaxel; Humans; Male; Middle Aged; Nitriles; Phenylthiohydantoin; Prostatic Neoplasms, Castration-Resistant; Radiopharmaceuticals; Radium; Retrospective Studies; Survival Rate; Taxoids

The ALSYMPCA study established a 3.6 month Overall Survival (OS) benefit in metastatic Castration Resistant Prostate Cancer (mCRPC) patients treated with Radium-223 dichloride (Ra-223) over placebo. Here we report clinical outcomes of Ra-223 treatment in a nonstudy population. In this prospective registry, patients from 20 Dutch hospitals were included prior to Ra-223 treatment. Clinical parameters collected included previous treatments and Adverse Events. Primary outcome was 6 months Symptomatic Skeletal Event (SSE)-free survival, while secondary outcomes included Progression-Free Survival (PFS) and Overall Survival (OS). Of the 305 patients included, 300 were evaluable. The mean age was 73.6 years, 90% had ≥6 bone metastases and 74.1% were pretreated with Docetaxel, 19.5% with Cabazitaxel and 80.5% with Abiraterone and/or Enzalutamide. Of all patients, 96.7% were treated with Ra-223 and received a median of 5 cycles. After a median follow-up of 13.2 months, 6 months SSE-free survival rate was 83%, median PFS was 5.1 months and median OS was 15.2 months. Six months SSE-free survival rate and OS were comparable with those reported in ALSYMPCA. "Previous Cabazitaxel treatment" and "bone-only metastases" were independent predictors of a shorter and longer PFS, respectively, while above-median LDH and "bone-only metastases" were independent predictors of shorter and longer OS, respectively. Toxicity was similar as reported in the ALSYMPCA trial. These results suggest that in a nonstudy population, Ra-223 treatment is well-tolerated, equally effective as in the ALSYMPCA population and that patients not previously treated with Cabazitaxel benefit most from Ra-223.

Topics: Aged; Aged, 80 and over; Androstenes; Antineoplastic Agents; Benzamides; Bone Neoplasms; Chemoradiotherapy; Docetaxel; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Nitriles; Outcome Assessment, Health Care; Phenylthiohydantoin; Prospective Studies; Prostatic Neoplasms, Castration-Resistant; Radium; Registries; Taxoids

Automated bone scan index (aBSI) change (ΔBSI) after treatment and survival in men with prostate cancer remains unclear. We evaluated the correlation between ΔBSI after cabazitaxel and overall survival (OS) in men with bone metastatic castration-resistant prostate cancer (CRPC).. We retrospectively enrolled 32 men with bone metastatic CRPC who had received cabazitaxel. The correlation between ΔBSI from baseline to 16 weeks after starting cabazitaxel and OS was analyzed by multivariate analysis.. Median age and time to CRPC were 70.7 years and 9.5 months, respectively. The median cycles of docetaxel before cabazitaxel were eight. Ten (31.2%) patients had visceral metastases at baseline. Median baseline prostate-specific antigen (PSA) was 123.0 ng/mL. The median aBSIs at baseline and 16 weeks after cabazitaxel were 3.2 and 4.4%, respectively. Improvements in aBSI and PSA after 16 weeks of cabazitaxel occurred in 7 (21.9%) and 12 patients (37.5%), respectively. There were no correlations between ΔBSI and OS (p = 0.55), but PSA change was significantly correlated with OS (p = 0.03) by multivariate analysis.. This study demonstrated that ΔBSI from baseline to16 weeks after starting cabazitaxel was not correlated with OS among men with bone metastatic CRPC. Further prospective studies may be warranted to confirm the limited utility of aBSI in this setting.

Topics: Aged; Aged, 80 and over; Bone Neoplasms; Correlation of Data; Humans; Male; Middle Aged; Prostatic Neoplasms, Castration-Resistant; Retrospective Studies; Survival Rate; Taxoids

Cabazitaxel is a treatment of metastatic castration-resistant prostate cancer (mCRPC) after docetaxel failure. The FUJI cohort aimed to confirm the real-life overall and progression-free survival (OS, PFS) and safety of cabazitaxel.. Multicentre, non-interventional cohort of French mCRPC patients initiating cabazitaxel between 2013 and 2015, followed 18 months.. Four hundred one patients were recruited in 42 centres. At inclusion, median age was 70, main metastatic sites were bones (87%), lymph nodes (42%) and visceral (20%). 18% had cabazitaxel in 2nd-line treatment, 39% in 3rd-line and 43% in 4th-line or beyond. All had prior docetaxel, and 82% prior abiraterone, enzalutamide or both. Median duration of cabazitaxel treatment was 3.4 months. Median OS from cabazitaxel initiation was 11.9 months [95% CI: 10.1-12.9]. In multivariate analyses, grade ≥ 3 adverse events, visceral metastases, polymedication, and >5 bone metastases were associated with a shorter OS. Main grade ≥ 3 adverse events were haematological with 8% febrile neutropenia.. Real-life survival with cabazitaxel in FUJI was shorter than in TROPIC (pivotal trial, median OS 15.1 months) or PROSELICA (clinical trial 20 vs 25 mg/m. It was registered with the European Medicines Agency EUPASS registry, available at www.encepp.eu, as EUPAS10391. It has been approved as an ENCEPP SEAL study.

Topics: Aged; Androstenes; Antineoplastic Combined Chemotherapy Protocols; Benzamides; Bone Neoplasms; Docetaxel; Humans; Kaplan-Meier Estimate; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Metastasis; Nitriles; Phenylthiohydantoin; Prednisone; Progression-Free Survival; Prostatic Neoplasms, Castration-Resistant; Taxoids; Treatment Outcome

To evaluate the association between prostate-specific antigen (PSA) response and progression-free and overall survival in men with metastatic castration-resistant prostate cancer (mCRPC) treated with cabazitaxel.. Of the 527 men (median age 72 years), 266 received ≥ 4 cycles of cabazitaxel and had PSA response data. After four cycles, 34.6% of men achieved a PSA decrease ≥ 50% and 49.6% a decrease ≥ 30%. Median progression-free survival was 7.7 (95% CI 6.2, 9.5) months, and overall survival was 19.5 (95% CI 16.0, 30.9) months, corresponding to 1-year event rates of 39.4 and 78.8%, respectively. Median progression-free survival was longer in PSA responders versus non-responders (15.7 vs 5.5 months at 50% cut-off; 15.7 vs 5.3 months for 30% cut-off; both P < 0.0001). Overall survival (50% cut-off) was 23.3 months in responders and 16.0 months in non-responders (P = 0.068); corresponding data at the 30% cut-off are 21.7 and 16.0 months (P = 0.057). Overall, 55.4% of men experienced ≥ 1 adverse event, 59.6% of whom had a serious adverse event.. PSA response after four cycles of cabazitaxel is associated with improved progression-free survival in men with mCRPC treated with cabazitaxel plus prednis(ol)one.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Bone Neoplasms; Disease-Free Survival; Humans; Kallikreins; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Metastasis; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Taxoids; Treatment Outcome

The purpose of the study was to define clinical factors for successful treatment response and re-exposure to docetaxel in metastatic castration-resistant prostate cancer (mCRPC).. An mCRPC database of patients receiving first-line docetaxel and rechallenge courses was established. Several clinical factors were evaluated for prediction of treatment response. Multivariate cox-regression analysis was used to define pre-treatment and treatment factors for survival.. Between 2005 and 2013, 94 patients with mCRPC were treated with docetaxel. Full data set and follow-up were available for 62 patients. Median follow-up was 84 m [interquartile range (IQR) 64-104 m]. Median biochemical progression-free survival (bPFS) and overall survival under docetaxel were 9 m (IQR 5-16 m) and 20 m (IQR 16-26 m), respectively. Partial PSA-response at first docetaxel-sequence (n = 62), rechallenge (n = 32), and third-sequence (n = 22) docetaxel was 48.4%, 31.6%, and 34.8%, respectively. Time from start of primary androgen deprivation to CRPC > 47 m was the only independent pre-treatment parameter to predict improved overall survival (Hazard Ratio 0.48, p = 0.015). Interestingly, there was a strong trend for improved overall survival in patients with high Gleason Score (Hazard Ratio 0.58; p = 0.08). Partial PSA-response at docetaxel-rechallenge (Hazard Ratio 0.31; p = 0.008) and treatment-free interval > 3 m (Hazard Ratio 3.49; p = 0.014) were the only independent predictive factors under taxane treatment for overall survival.. Despite novel hormonal drugs, docetaxel still plays an important role in the treatment of mCRPC. Patients with partial-PSA-response at rechallenge or a treatment-free interval > 3 m benefit most from docetaxel re-exposure.

Topics: Aged; Androstenes; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Disease-Free Survival; Docetaxel; Follow-Up Studies; Gonadotropin-Releasing Hormone; Humans; Lymphatic Metastasis; Male; Middle Aged; Mitoxantrone; Neoplasm Grading; Orchiectomy; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms, Castration-Resistant; Retreatment; Retrospective Studies; Survival Rate; Taxoids

The aim of this study was to develop a novel cabazitaxel bone targeted nanoparticle (NP) system for improved drug delivery to the bone microenvironment.. Nanoparticles were developed using poly(D,L-lactic-co-glycolic acid) and cabazitaxel as the core with amino-bisphosphonate surface conjugation. Optimization of nanoparticle physiochemical properties, in vitro evaluation in prostate cancer cell lines and in vivo testing in an intraosseous model of metastatic prostate cancer was performed.. This bone targeted cabazitaxel nanocarrier system showed significant reduction in tumor burden, while at the same time maintaining bone structure integrity and reducing pain in the mouse tumor limb.. This bone microenvironment targeted nanoparticle system and clinically relevant approach of evaluation represents a promising advancement for treating bone metastatic cancer.

Topics: Animals; Antineoplastic Agents; Bone and Bones; Bone Neoplasms; Cell Line, Tumor; Cell Survival; Diphosphonates; Drug Carriers; Drug Liberation; Humans; Lactic Acid; Male; Mice; Mice, Nude; Nanoparticles; Pain; Particle Size; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Prostatic Neoplasms; Surface Properties; Taxoids; Xenograft Model Antitumor Assays

Effective treatment of metastatic castration resistant prostate cancer (mCRPC) remains an unmet challenge. Cabazitaxel (CBZ) is approved for mCRPC after docetaxel (DTX) failure, but the improvement in survival is only moderate (∼2 months) and patients suffer from significant side effects. Here, we report the development of a polymer based delivery system for CBZ to improve its safety and efficacy against DTX-resistant mCRPC. CBZ was conjugated to a carboxymethylcellulose-based polymer (Cellax-CBZ), which self-assembled into ∼100 nm particles in saline and exhibited sustained drug release in serum at 10%/day. Cellax-CBZ delivered 157-fold higher CBZ to PC3-RES prostate tumor in mice and could be safely administered at a 25-fold higher dose compared to free CBZ, resulting in superior tumor inhibition in multiple mice models of DTX-resistant CRPC. In a metastatic bone model of CRPC, Cellax-CBZ significantly improves overall survival with a 70% long-term survival rate to day 120, while mice treated with free CBZ had a median survival of 40 days. Cellax-CBZ induced mild and reversible neutropenia in mice but no other tissue damage. Cellax-CBZ showed significant potential for improving therapy of mCRPC over clinically approved CBZ.

Topics: Animals; Antineoplastic Agents; Bone Neoplasms; Carboxymethylcellulose Sodium; Cell Line, Tumor; Delayed-Action Preparations; Docetaxel; Drug Carriers; Drug Compounding; Drug Liberation; Drug Resistance, Neoplasm; Humans; Male; Maximum Tolerated Dose; Mice, Inbred NOD; Mice, SCID; Nanoparticles; Neutropenia; Particle Size; Prostatic Neoplasms, Castration-Resistant; Solubility; Taxoids; Tissue Distribution; Xenograft Model Antitumor Assays

Rhenium-188-HEDP is an effective radiopharmaceutical for the treatment of painful bone metastases from prostate cancer. The effectiveness of the β-radiation emitted by. The cytotoxic effects of single and combined treatment with taxanes and. The survival curves showed dose-dependent cell growth inhibition for both the taxanes and. This proof-of-mechanism study exploring radiosensitization by combining

Topics: Antineoplastic Agents; Bone Neoplasms; Cell Line, Tumor; Chemoradiotherapy; Chemotherapy, Adjuvant; DNA Repair; Docetaxel; Dose-Response Relationship, Drug; Etidronic Acid; Humans; Male; Organometallic Compounds; Prostatic Neoplasms; Radiation-Sensitizing Agents; Radiopharmaceuticals; Taxoids

To evaluate the efficacy of enzalutamide (Enz) as fourth- or fifth-line treatment in men with metastasized castration-resistant prostate cancer (mCRPC), by analyzing a retrospective cohort of heavily pretreated patients.. We evaluated toxicity, overall survival (OS), progression-free survival (PFS) and time to prostate-specific antigen (PSA) progression data from 47 CRPC patients treated with fourth- or fifth-line Enz.. All patients were treated with docetaxel and abiraterone acetate and 42 patients (89%) with cabazitaxel. The median age of the patients was 69 years (IQR, 63-73.5), 79% had bone metastases, 55% had lymph node metastases, and 17% had visceral metastases. The median duration of Enz treatment was 12.0 weeks (IQR, 8.3-20.4), and 11 patients (23%) responded to Enz (maximum PSA decline ≥50%). In general, Enz was well tolerated, with the most frequently reported adverse events being fatigue and nausea. The median OS was 40.1 weeks (95% CI, 25.4-61.4), the median PFS was 12.1 weeks (95% CI, 9.9-14.0) and the median time to PSA progression was 15.7 weeks (95% CI, 14.0-28.7).. Analysis of this retrospective cohort suggests that Enz is well tolerated and that there is a 23% response rate in heavily pretreated CRPC patients, which is comparable with third-line treatment outcomes.

Topics: Abdominal Neoplasms; Abiraterone Acetate; Aged; Antineoplastic Agents; Benzamides; Bone Neoplasms; Disease Progression; Disease-Free Survival; Docetaxel; Humans; Lymphatic Metastasis; Male; Middle Aged; Nitriles; Phenylthiohydantoin; Prostatic Neoplasms, Castration-Resistant; Radioisotopes; Radium; Retreatment; Retrospective Studies; Survival Rate; Taxoids

Optimal sequencing of cabazitaxel (C) and abiraterone acetate (A) after docetaxel (D) for metastatic castration-resistant prostate cancer (mCRPC) is unclear. We assessed treatment patterns and outcomes in patients with mCRPC receiving different sequences of A or C, or both, after administration of D.. Retrospective analysis was conducted of US Oncology Network iKnowMed (iKM) electronic health record (EHR) data to assess patients with mCRPC who received treatment with D and were subsequently treated with C or A, or both, between April 2011 and May 2012. Patients received 2 or 3 drugs: DA, DC, DAC, or DCA. Overall survival (OS) and time to treatment failure (TTF) were analyzed by the Kaplan-Meier method from the start to the end of second-line therapy after administration of D (TTF1) and to the end of combined second- and third-line therapy (TTF2) for 3-drug sequences. Multivariable Cox proportional hazard models evaluated the impact of baseline clinical prognostic factors and treatment sequence on OS and TTF.. Of 350 patients who were treated with D and subsequent therapies, 183 (52.3%) received DA, 54 (15.4%) received DC, 77 (22.0%) received DCA, and 36 (10.3%) received DAC. In a multivariable analysis, adjusted comparisons suggested that 3-drug sequences were associated with improved OS versus 2-drug sequences (hazard ratio [HR], 0.21; 95% confidence interval [CI], 0.092-0.476; P = .0002). There were no statistically significant differences in OS and TTF for DC versus DA, and OS was significantly greater for DCA versus DAC (HR, 0.13; 95% CI, 0.022-0.733; P = .0210). More cycles of C were administered in DCA than in DAC (median 6 vs. 4; t test P < .0001), whereas the duration of A treatment was similar.. Administration of 3 agents in the DCA sequence was more optimal for treating mCRPC in this hypothesis-generating study.

Topics: Abiraterone Acetate; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Disease-Free Survival; Docetaxel; Drug Administration Schedule; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Proportional Hazards Models; Prostatic Neoplasms, Castration-Resistant; Retrospective Studies; Taxoids; Treatment Outcome

Topics: Antineoplastic Agents; Biomarkers, Tumor; Bone Neoplasms; Caenorhabditis elegans Proteins; Health Status Indicators; Humans; Male; Prostatic Neoplasms, Castration-Resistant; Quality of Life; Taxoids; Ubiquitin-Conjugating Enzymes

Interactive case studies formed a key feature of the third annual Interactive Genitourinary Cancer Conference held in April/May 2011 in Budapest, Hungary. These cases were used to discuss the practical aspects of the management of metastatic castration-resistant prostate cancer (mCRPC). Particular emphasis was placed on audience participation with potential management options posed as interactive questions to the delegates. This paper summarises these case studies and the related discussion. Docetaxel is the standard first-line chemotherapeutic agent for patients with mCRPC and, until recently, second-line therapeutic options were limited. Results from the recently completed TROPIC trial showed a statistically and clinically significant improvement in overall survival with the microtubule inhibitor cabazitaxel compared with mitoxantrone. Cabazitaxel has been shown to be well tolerated and has been approved in Europe and the USA as second-line chemotherapy for mCRPC. Prognostic factors have a potential benefit in individualised patient management in mCRPC. Pretreatment prognostic factors, including PSA doubling time, pain, visceral metastases, anaemia and progression of osseous metastases, have been shown to predict survival outcomes and can be used to guide treatment strategies, including appropriate timing of chemotherapy.   Multiple treatment options and significant heterogeneity among patients with advanced prostate cancer necessitate multidisciplinary team management in addition to patient education, as part of a patient-centred approach. The development of second-line chemotherapeutic agents together with the use of prognostic factors and a patient-centred multidisciplinary team approach provide encouraging new management prospects for patients with mCRPC.

Topics: Aged; Androgen Antagonists; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Congresses as Topic; Docetaxel; Drug Resistance, Neoplasm; Humans; Liver Neoplasms; Male; Palliative Care; Patient-Centered Care; Prognosis; Prostatectomy; Prostatic Neoplasms; Radiotherapy, Adjuvant; Taxoids

Topics: Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Docetaxel; Drug Resistance, Neoplasm; Fatal Outcome; Humans; Male; Neoplasm Recurrence, Local; Prednisolone; Prostate-Specific Antigen; Prostatic Neoplasms; Taxoids; Treatment Outcome

Clearly, no neoplasm other than prostate cancer has benefited from so many breakthroughs since the beginning of this decade: the past two years can be considered exceptional due to the number of emerging agents against castration-resistant prostate cancer (CRPC), which have demonstrated positive outcomes in phase III trials. Until 2010, docetaxel (Taxotere) was the only agent capable of improving survival in patients with metastatic CRPC. Since then, positive results from phase III trials have been reported for sipuleucel-T, cabazitaxel, denosumab, abiraterone, radium-223, and enzalutamide, while other promising agents including notably orteronel, ipilimumab and cabozantinib are currently under study. Taken together, the incorporation of these agents in the routine management of patients with CRPC is likely to expand their median life expectancy, which was only ∼1 year until the early 2000, to >30 months in the near future. The availability of these agents will lead to new challenges and questions, such as: Can our societies afford the costs? Should we use these agents sequentially or in combination with an incremental benefit? Can we personalise treatment based on the biology of the individual's disease? How will we develop new active compounds in the context where a half dozen approved agents may confound their potential overall survival effect?

Topics: Androgen Antagonists; Androstenes; Androstenols; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Hormonal; Bone Neoplasms; Clinical Trials, Phase III as Topic; Denosumab; Docetaxel; Humans; Ipilimumab; Male; Neoplasms, Hormone-Dependent; Orchiectomy; Prostate-Specific Antigen; Prostatic Neoplasms; Taxoids; Tissue Extracts; Tumor Microenvironment

Discoveries of molecular mechanisms and therapeutic targets in metastatic castration-resistant prostate cancer (CRPC) have led to significant advancements in the development of effective agents in this setting, with diverse mechanisms of action. Within the past 2 years, 5 agents have been approved for the treatment of patients with metastatic CRPC (cabazitaxel, abiraterone, sipuleucel-T, denosumab, and enzalutamide), and another (Alpharadin) has shown overall survival benefit in a phase III trial. This article summarizes the phase III data showing clinical benefit from these agents, highlights other promising therapies in phase III studies as single agents (PROSTVAC-VF, ipilimumab, cabozantinib), discusses important unanswered questions regarding these therapies, and provides a schema for their use based on current regulatory approval and how this is likely to evolve as data from ongoing studies are reported. Although curative interventions in metastatic CRPC still do not exist, the hope is that optimization of therapeutic strategies can reduce the morbidity and mortality associated with this disease.

Topics: Antineoplastic Agents, Hormonal; Bone Neoplasms; Clinical Trials, Phase III as Topic; Humans; Immunotherapy; Male; Molecular Targeted Therapy; Neoplasms, Hormone-Dependent; Prostatic Neoplasms; Radiopharmaceuticals; Taxoids

The biological basis of the selective outgrowth of disseminated prostate cancer cells within the hematopoietic bone microenvironment remains a compelling biological mystery. A major proportion of the morbidity and mortality related to prostate cancer can be traced to the burden of bone metastases. The optimal management of bone health in men with prostate cancer requires control of the underlying epithelial neoplasm, attenuation of the subverted bone remodeling process that accompanies disease progression, reduction in the bone complications of disease-directed therapy, and management of co-existing comorbidities that enhance bone fragility. While bone-homing radioisotopes, bisphosphonates, and RANK ligand inhibitors have demonstrated reduction in bone pain and/or other skeletal-related events, further advances into definitive improvements in survival and/or global quality of life are required. A deeper understanding of the biology of bone metastases will likely facilitate a bone-directed therapeutic approach toward a major impact on the survival of men with this important disease.

Topics: Androstenes; Androstenols; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Bone Neoplasms; Clinical Trials as Topic; Denosumab; Diphosphonates; Humans; Male; Prostatic Neoplasms; RANK Ligand; Taxoids; Tissue Extracts