Nevertheless, recent preliminary data of an ongoing, double-blind, placebo-controlled phase III trial in metastatic CRPC comparing radium-223 dichloride with placebo, both given in combination with abiraterone and prednisone/prednisolone, have indicated that combined use of these medications may be associated with increased risk of death and fractures. ![]() Initial results regarding concurrent administration of radium-223 dichloride with docetaxel or anti-androgen therapies seemed promising regarding tolerance and safety of the concomitant therapies. These results suggested the suitability of the agent for combined use with other medications. This study demonstrated an improvement of overall survival as well as delaying of time to first symptomatic skeletal event with the use of radium-223 dichloride, and led to its Food and Drug Administration (FDA) approval in 2013 for the treatment of CRPC patients with symptomatic bone metastases and no known visceral metastatic disease.īesides its efficacy in controlling metastatic bone disease, the ALSYMPCA trial highlighted another significant feature of radium-223 dichloride, namely its favorable safety profile ALSYMPCA’s final long-term safety analysis confirmed low myelosuppression incidence and further showed that treatment remained well tolerated, with no new safety concerns. Unlike previous radiopharmaceuticals, radium-223 dichloride (Xofigo ®) has been the first targeted, α-particle-emitting agent to show a survival benefit in castration-resistant PC (CRPC) patients with bone metastases, as demonstrated in the landmark ALSYMPCA trial. Historically, radionuclide therapy has been applied for decades in the treatment of bone metastases with bone-modifying, β-particle-emitting agents (like strontium-89 and samarium-153), but their use has been mainly palliative and without clear survival benefit when applied as monotherapy. Several classes of bone-targeting therapies have been developed and introduced in clinical practice for the treatment of PC-related bone metastases, some of which have a proven capacity to improve survival, and others with rather supportive or palliative role. The skeleton is the major metastatic site in PC with more than 90% of patients dying from PC having bone metastases. Conclusions: While more prospective studies are needed to fully characterize the toxicological profile of radium-223 dichloride, the present work constitutes perhaps the first effort to examine its safety when administered alone and in combination with other agents based on computational evidence from public real-world post marketing data.ĭevelopment of bone metastases represents a pivotal incident in the clinical course of prostate cancer (PC), associated with the appearance of skeletal-related events, a decrease in quality of life and an increase in mortality. Our analysis demonstrates that radium-223 dichloride may often come with hematological-related reactions, and that, when administered together with other drugs, its safety profile may differ. ![]() Results: A total of ~1500 prostate cancer patients treated with radium-223 dichloride was identified, and side effects reported with the use of radium-223 dichloride alone or in combination with other therapeutic agents were extracted. ![]() Materials and Methods: We performed a retrospective analysis of cases extracted from the FDA Adverse Event Reporting System and characterized side effect occurrence by using reporting ratios. The aim of our present study is to assess whether accessible sources of patient outcome data can help gain additional clinical insights to radium-223 dichloride’s safety profile. While the precise pathophysiologic mechanisms of these events are not yet clear, collecting evidence from more clinical trials and translational studies is necessary. Nevertheless, recent evidence suggests that its combined use with abiraterone and prednisone/prednisolone may be associated with increased risk of death and fractures. This targeted, α-particle-emitting therapy has demonstrated significant survival benefit accompanied by a favorable safety profile. ![]() Background and Objective: Radium-223 dichloride (Xofigo ®) is a calcium mimetic agent approved for the treatment of castration-resistant prostate cancer patients with symptomatic bone metastases and no known visceral metastatic disease.
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