Bone metastases have a major impact on quality of life and survival of patients with advanced prostate cancer,in the last decade,the development and approval of substances inhibiting the vicious cycle of bone metastas...Bone metastases have a major impact on quality of life and survival of patients with advanced prostate cancer,in the last decade,the development and approval of substances inhibiting the vicious cycle of bone metastases have enabled the reduction of complications caused by bone metastases in patients with castration-resistant prostate cancer.These drugs have raised awareness of the importance of skeletal-related events which in the meantime represent an important end point also in trials using agents not specifically designed for bone lesions.Second-generation antihormona]drugs such as enzalutamide or abiraterone have been shown to have a positive impact on the incidence of skeletal complications and therefore provide an important tool in the armamentarium used for treating bone metastases.Radiopharmaceuticals such as radium-223 dichloride([^223Ra])have been demonstrated not only to reduce skeletal-related events and bone-related pain,but also to prolong overall survival,thereby being the first bone-targeting agent showing a survival benefit.As previous studies have not provided an obvious benefit of bone-targeted lesions in castration-sensitive disease,the use of these agents is not recommended.In oligometastatic prostate cancer,the role of local treatment of metastases using stereotactic radiation or radiosurgery is a matter of intense debates and may play an increasing role in the future.展开更多
In 2004, docetaxel was approved for the treatment of metastatic castration-resistant prostate cancer （mCRPC）. For the next several years, there was a lull in drug approvals. However, from 2010 onwards, 5 additional ...In 2004, docetaxel was approved for the treatment of metastatic castration-resistant prostate cancer （mCRPC）. For the next several years, there was a lull in drug approvals. However, from 2010 onwards, 5 additional therapies have been approved on the basis of showing a survival benefit in phase III studies. These agents include sipuleuceI-T, cabazitaxel, abiraterone, enzalutamide and （most recently） radium-223. Amongst radiopharmaceuticals currently used for advanced prostate cancer （e.g. samarium-153 and strontium-89）, radium-223 possesses several unique properties. As an alpha-emitting compound, the agent produces a high-energy output over a short range, facilitating selective destruction of tissue within the bone in the region of osteoblastic lesions while sparing surrounding normal tissue. The current review will outline biological rationale for radium-223 and also provide an overview of preclinical and clinical development of the agent. Rational sequencing of radium-223 and combinations, in the increasingly complex landscape of mCRPC will be discussed, along with factors influencing clinical implementation.展开更多
Objectives: The aim of this study was to describe the diagnostic and etiological aspects of bone metastases in the Rheumatology Department of Cocody’s University Teaching Hospital (UTH). Methodology: This was a descr...Objectives: The aim of this study was to describe the diagnostic and etiological aspects of bone metastases in the Rheumatology Department of Cocody’s University Teaching Hospital (UTH). Methodology: This was a descriptive, 11-year retrospective study (January 1, 2006 to December 31, 2016) of inpatient records of bone metastases. The diagnosis was made on clinical (bone signs), radiological (osteolysis, bone condensation) and sometimes histological basis. Result: Eighty out of 6, 1111 inpatients suffered from bone metastasis with a hospital frequency of 1.30%. The average age was 60.74 years (range 26 to 81 years). Men were predominant (53 men for 27 women) with a sex ratio of 1.96. The main complaints were pain (97.6%). chronic (90%), severe (73.8%), inflammatory (93.8%). There was sometimes a neurological complication: a motor deficit (21.3%), sensitive (13.8%). These symptoms were associated with fever (56.3%) and altered general state (85%). Bone metastases have been revealing in the vast majority of cases (93.75%);the primary cancer was known only in 5 patients (prostate = 2, breast = 2 and cervix = 1). Bone condensation (61.3%), osteolysis (50%) and mixed lesions (7.5%) where the main radiological lesions observed. The primary tumors were: prostatic (50%), pulmonary (18.8%), mammary (11.3%), uterine (5%), renal (2.5%), hepatic (2.5%), bladder (1.3%) and adrenal (1.3%). Conclusion: Bone metastases affect mostly the elderly;inflammatory spinal pain is the main symptom. Bone condensation is the most common radiologic lesion. The prostate, breast and lungs are the main primary tumors.展开更多
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 act...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. A deeper insight into this hypothetical mechanism will lead to a more accurate dosimetric approach and to find optimal sequencing and/or combination with the other therapeutic options.展开更多
Bone metastases are the main driver of morbidity and mortality in advanced prostate cancer. Targeting the bone microenvironment, a key player in the pathogenesis of bone metastasis, has become one of the mainstays of ...Bone metastases are the main driver of morbidity and mortality in advanced prostate cancer. Targeting the bone microenvironment, a key player in the pathogenesis of bone metastasis, has become one of the mainstays of therapy in men with advanced prostate cancer. This review will evaluate the data supporting the use of bone-targeted therapy, including （1） bisphosphonates such as zoledronic acid, which directly target osteoclasts, （2） denosumab, a receptor activator of nuclear factor-kappa B （RANK） ligand inhibitor, which targets a key component of bone stromal interaction, and （3） radium-223, an alpha-emitting calcium mimetic, which hones to the metabolically active areas of osteoblastic metastasis and induces double-strand breaks in the DNA. Denosumab has shown enhanced delay in skeletal-related events compared to zoledronic acid in patients with metastatic castration-resistant prostate cancer （mCRPC）. Data are mixed with regard to pain control as a primary measure of efficacy. New data call into question dosing frequency, with quarterly dosing strategy potentially achieving similar effect compared to monthly dosing for zoledronic acid. In the case of radium-223, there are data for both pain palliation and improved overall survival in mCRPC. Further studies are needed to optimize timing and combination strategies for bone-targeted therapies. Ongoing studies will explore the impact of combining bone-targeted therapy with investigational therapeutic agents such as immunotherapy, for advanced prostate cancer. Future studies should strive to develop biomarkers of response, in order to improve efficacy and cost-effectiveness of these agents.展开更多
文摘Bone metastases have a major impact on quality of life and survival of patients with advanced prostate cancer,in the last decade,the development and approval of substances inhibiting the vicious cycle of bone metastases have enabled the reduction of complications caused by bone metastases in patients with castration-resistant prostate cancer.These drugs have raised awareness of the importance of skeletal-related events which in the meantime represent an important end point also in trials using agents not specifically designed for bone lesions.Second-generation antihormona]drugs such as enzalutamide or abiraterone have been shown to have a positive impact on the incidence of skeletal complications and therefore provide an important tool in the armamentarium used for treating bone metastases.Radiopharmaceuticals such as radium-223 dichloride([^223Ra])have been demonstrated not only to reduce skeletal-related events and bone-related pain,but also to prolong overall survival,thereby being the first bone-targeting agent showing a survival benefit.As previous studies have not provided an obvious benefit of bone-targeted lesions in castration-sensitive disease,the use of these agents is not recommended.In oligometastatic prostate cancer,the role of local treatment of metastases using stereotactic radiation or radiosurgery is a matter of intense debates and may play an increasing role in the future.
文摘In 2004, docetaxel was approved for the treatment of metastatic castration-resistant prostate cancer （mCRPC）. For the next several years, there was a lull in drug approvals. However, from 2010 onwards, 5 additional therapies have been approved on the basis of showing a survival benefit in phase III studies. These agents include sipuleuceI-T, cabazitaxel, abiraterone, enzalutamide and （most recently） radium-223. Amongst radiopharmaceuticals currently used for advanced prostate cancer （e.g. samarium-153 and strontium-89）, radium-223 possesses several unique properties. As an alpha-emitting compound, the agent produces a high-energy output over a short range, facilitating selective destruction of tissue within the bone in the region of osteoblastic lesions while sparing surrounding normal tissue. The current review will outline biological rationale for radium-223 and also provide an overview of preclinical and clinical development of the agent. Rational sequencing of radium-223 and combinations, in the increasingly complex landscape of mCRPC will be discussed, along with factors influencing clinical implementation.
文摘Objectives: The aim of this study was to describe the diagnostic and etiological aspects of bone metastases in the Rheumatology Department of Cocody’s University Teaching Hospital (UTH). Methodology: This was a descriptive, 11-year retrospective study (January 1, 2006 to December 31, 2016) of inpatient records of bone metastases. The diagnosis was made on clinical (bone signs), radiological (osteolysis, bone condensation) and sometimes histological basis. Result: Eighty out of 6, 1111 inpatients suffered from bone metastasis with a hospital frequency of 1.30%. The average age was 60.74 years (range 26 to 81 years). Men were predominant (53 men for 27 women) with a sex ratio of 1.96. The main complaints were pain (97.6%). chronic (90%), severe (73.8%), inflammatory (93.8%). There was sometimes a neurological complication: a motor deficit (21.3%), sensitive (13.8%). These symptoms were associated with fever (56.3%) and altered general state (85%). Bone metastases have been revealing in the vast majority of cases (93.75%);the primary cancer was known only in 5 patients (prostate = 2, breast = 2 and cervix = 1). Bone condensation (61.3%), osteolysis (50%) and mixed lesions (7.5%) where the main radiological lesions observed. The primary tumors were: prostatic (50%), pulmonary (18.8%), mammary (11.3%), uterine (5%), renal (2.5%), hepatic (2.5%), bladder (1.3%) and adrenal (1.3%). Conclusion: Bone metastases affect mostly the elderly;inflammatory spinal pain is the main symptom. Bone condensation is the most common radiologic lesion. The prostate, breast and lungs are the main primary tumors.
文摘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. A deeper insight into this hypothetical mechanism will lead to a more accurate dosimetric approach and to find optimal sequencing and/or combination with the other therapeutic options.
文摘Bone metastases are the main driver of morbidity and mortality in advanced prostate cancer. Targeting the bone microenvironment, a key player in the pathogenesis of bone metastasis, has become one of the mainstays of therapy in men with advanced prostate cancer. This review will evaluate the data supporting the use of bone-targeted therapy, including （1） bisphosphonates such as zoledronic acid, which directly target osteoclasts, （2） denosumab, a receptor activator of nuclear factor-kappa B （RANK） ligand inhibitor, which targets a key component of bone stromal interaction, and （3） radium-223, an alpha-emitting calcium mimetic, which hones to the metabolically active areas of osteoblastic metastasis and induces double-strand breaks in the DNA. Denosumab has shown enhanced delay in skeletal-related events compared to zoledronic acid in patients with metastatic castration-resistant prostate cancer （mCRPC）. Data are mixed with regard to pain control as a primary measure of efficacy. New data call into question dosing frequency, with quarterly dosing strategy potentially achieving similar effect compared to monthly dosing for zoledronic acid. In the case of radium-223, there are data for both pain palliation and improved overall survival in mCRPC. Further studies are needed to optimize timing and combination strategies for bone-targeted therapies. Ongoing studies will explore the impact of combining bone-targeted therapy with investigational therapeutic agents such as immunotherapy, for advanced prostate cancer. Future studies should strive to develop biomarkers of response, in order to improve efficacy and cost-effectiveness of these agents.
