Purpose: The purpose of this paper is to discuss the most important facts about prostate cancer, its treatments and efficacy, the type of prostate cancer that does not improve with hormonal therapy (Castration-Resista...Purpose: The purpose of this paper is to discuss the most important facts about prostate cancer, its treatments and efficacy, the type of prostate cancer that does not improve with hormonal therapy (Castration-Resistant Prostate Cancer-CRPC), and the recently approved Radium-223 dichloride targeted therapy for CRPC that has metastasized to bones. Prostate cancer is the third most common malignancy diagnosed worldwide and the most common malignant disease in men. Also, the incidence of prostate cancer varies between regions. So it’s important to have a proper understanding of all above points to prevent the further development and spread of cancer and improve the cure rate. Design: The paper begins by discussing what prostate cancer is, the risk factors, clinical manifestations, and the treatments for prostate cancer. It covers the clinical manifestations, pathology, screening (cancer biomarker Prostate Specific Antigen, Digital Rectal Examination—DRE, prostate biopsy, and imaging) and treatments for prostate cancer. The paper then delves into the main treatment methods for prostate cancer, including how Castration-Resistant Prostate Cancer (CRPC) differs from normal prostate cancer after hormone suppression therapy. Additionally, it discusses the effectiveness of the recently introduced Radium-223 dichloride injection as a radiation-targeted therapy for treating CRPC that has metastasized to bones. This section covers the properties of radium-223 dichloride injection, its pharmacokinetics, pharmacodynamics, absorption and volume of distribution, half-life, metabolism, route of elimination, clearance, toxicity, adverse effects, and mechanism of action at the tumor site. It also discusses preclinical studies related to radium-223 dichloride injection and its effectiveness in treating CRPC patients with bone metastasis. Conclusion: Prostate cancer is a common cancer that can be treated with surgery or hormonal therapy. However, if the cancer progresses despite hormonal therapy, Radium-223 dichloride injection can be used as a radiation target therapy to treat patients with CRPC and symptomatic bone metastases. This treatment kills tumor cells in bones and reduces associated pain with minimal damage to surrounding normal tissue. However, the metastatic disease cannot be cured and can only offer palliation for the patient. Suggestions: Based on the facts, Radium-223 target therapy is effective in treating and providing palliation for cancers. It is suggested to further develop the usage of radiation target therapy and to test the safety and efficacy of more than 6 injections of Radium-223 dichloride and its combination with currently used chemotherapy drugs for bone metastasized CRPC. This paper aims to contribute to future research designs related to cancer therapies using radiation and to design new studies and practical implementations, especially regarding the usage of radium-223 dichloride.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
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
Patients with bone metastatic castration-resistant prostate cancer (mCRPC) might benefit from radium-223 (^(223)Ra) combined withnew-generation hormonal agents (NHAs) in terms of survival and quality of life (QoL). Ho...Patients with bone metastatic castration-resistant prostate cancer (mCRPC) might benefit from radium-223 (^(223)Ra) combined withnew-generation hormonal agents (NHAs) in terms of survival and quality of life (QoL). However, the safety of combination therapiesremains unclear. Therefore, we aimed to perform a network meta-analysis by reviewing the literature about the combination of^(223)Ra with abiraterone acetate plus prednisone (AAP) or enzalutamide and to evaluate the safety of combination therapy in bonemCRPC patients. Ultimately, ten studies (2835 patients) were selected, including four randomized controlled trials (RCTs), fiveretrospective cohort studies, and one single-arm study. Overall, there was no difference in the incidence of fracture between the^(223)Ra+NHA combination group and the ^(223)Ra monotherapy group (odds ratio [OR]: 1.46, 95% confidence interval [CI]: 0.91–2.34,P = 0.66), but the incidences in both the ^(223)Ra+NHA combination group (OR: 3.22, 95% CI: 2.24–4.63, P < 0.01) and the ^(223)Ramonotherapy group (OR: 2.24, 95% CI: 1.23–4.08, P < 0.01) were higher than that in the NHA monotherapy group. However, inthe meta-analysis involving only RCTs, there was no difference between the ^(223)Ra monotherapy group and the NHA monotherapygroup (OR: 1.14, 95% CI: 0.22–5.95, P = 0.88), while the difference between the ^(223)Ra+NHA combination group and the NHAmonotherapy group remained significant (OR: 3.22, 95% CI: 2.24–4.63, P < 0.01). Symptomatic skeletal events (SSEs), SSE-freesurvival (SSE-FS), all grades of common adverse events (AEs), and ≥grade 3 AEs among all groups did not show any significantdifference. Our results indicate that the combination of ^(223)Ra with NHAs was well tolerated in bone mCRPC patients compared to ^(223)Ra monotherapy, even though the incidence of fracture was higher in patients who received ^(223)Ra than that among those whoreceived NHA monotherapy. More evidence is needed to explore the safety and efficiency of ^(223)Ra combination therapies.展开更多
文摘Purpose: The purpose of this paper is to discuss the most important facts about prostate cancer, its treatments and efficacy, the type of prostate cancer that does not improve with hormonal therapy (Castration-Resistant Prostate Cancer-CRPC), and the recently approved Radium-223 dichloride targeted therapy for CRPC that has metastasized to bones. Prostate cancer is the third most common malignancy diagnosed worldwide and the most common malignant disease in men. Also, the incidence of prostate cancer varies between regions. So it’s important to have a proper understanding of all above points to prevent the further development and spread of cancer and improve the cure rate. Design: The paper begins by discussing what prostate cancer is, the risk factors, clinical manifestations, and the treatments for prostate cancer. It covers the clinical manifestations, pathology, screening (cancer biomarker Prostate Specific Antigen, Digital Rectal Examination—DRE, prostate biopsy, and imaging) and treatments for prostate cancer. The paper then delves into the main treatment methods for prostate cancer, including how Castration-Resistant Prostate Cancer (CRPC) differs from normal prostate cancer after hormone suppression therapy. Additionally, it discusses the effectiveness of the recently introduced Radium-223 dichloride injection as a radiation-targeted therapy for treating CRPC that has metastasized to bones. This section covers the properties of radium-223 dichloride injection, its pharmacokinetics, pharmacodynamics, absorption and volume of distribution, half-life, metabolism, route of elimination, clearance, toxicity, adverse effects, and mechanism of action at the tumor site. It also discusses preclinical studies related to radium-223 dichloride injection and its effectiveness in treating CRPC patients with bone metastasis. Conclusion: Prostate cancer is a common cancer that can be treated with surgery or hormonal therapy. However, if the cancer progresses despite hormonal therapy, Radium-223 dichloride injection can be used as a radiation target therapy to treat patients with CRPC and symptomatic bone metastases. This treatment kills tumor cells in bones and reduces associated pain with minimal damage to surrounding normal tissue. However, the metastatic disease cannot be cured and can only offer palliation for the patient. Suggestions: Based on the facts, Radium-223 target therapy is effective in treating and providing palliation for cancers. It is suggested to further develop the usage of radiation target therapy and to test the safety and efficacy of more than 6 injections of Radium-223 dichloride and its combination with currently used chemotherapy drugs for bone metastasized CRPC. This paper aims to contribute to future research designs related to cancer therapies using radiation and to design new studies and practical implementations, especially regarding the usage of radium-223 dichloride.
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.
基金supported by the Science and Technology Support Program of Sichuan Province(2021YFS0119)the Natural Science Foundation of China(No.82172785,81902577,81974398,and 81872107)+1 种基金Research Foundation for the Postdoctoral Program of Sichuan University(2021SCU12014)1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University(ZYJC21020).
文摘Patients with bone metastatic castration-resistant prostate cancer (mCRPC) might benefit from radium-223 (^(223)Ra) combined withnew-generation hormonal agents (NHAs) in terms of survival and quality of life (QoL). However, the safety of combination therapiesremains unclear. Therefore, we aimed to perform a network meta-analysis by reviewing the literature about the combination of^(223)Ra with abiraterone acetate plus prednisone (AAP) or enzalutamide and to evaluate the safety of combination therapy in bonemCRPC patients. Ultimately, ten studies (2835 patients) were selected, including four randomized controlled trials (RCTs), fiveretrospective cohort studies, and one single-arm study. Overall, there was no difference in the incidence of fracture between the^(223)Ra+NHA combination group and the ^(223)Ra monotherapy group (odds ratio [OR]: 1.46, 95% confidence interval [CI]: 0.91–2.34,P = 0.66), but the incidences in both the ^(223)Ra+NHA combination group (OR: 3.22, 95% CI: 2.24–4.63, P < 0.01) and the ^(223)Ramonotherapy group (OR: 2.24, 95% CI: 1.23–4.08, P < 0.01) were higher than that in the NHA monotherapy group. However, inthe meta-analysis involving only RCTs, there was no difference between the ^(223)Ra monotherapy group and the NHA monotherapygroup (OR: 1.14, 95% CI: 0.22–5.95, P = 0.88), while the difference between the ^(223)Ra+NHA combination group and the NHAmonotherapy group remained significant (OR: 3.22, 95% CI: 2.24–4.63, P < 0.01). Symptomatic skeletal events (SSEs), SSE-freesurvival (SSE-FS), all grades of common adverse events (AEs), and ≥grade 3 AEs among all groups did not show any significantdifference. Our results indicate that the combination of ^(223)Ra with NHAs was well tolerated in bone mCRPC patients compared to ^(223)Ra monotherapy, even though the incidence of fracture was higher in patients who received ^(223)Ra than that among those whoreceived NHA monotherapy. More evidence is needed to explore the safety and efficiency of ^(223)Ra combination therapies.
