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Radium 2237/6/2023 CONCLUSIONS: Osteomimicry may contribute in part to the uptake of radium-223 within bone metastases and may thereby enhance the therapeutic benefit of this bone targeting radiotherapy. We identified genomic gains in osteoblast mimicry genes including gains of ALPL, osteopontin, SPARC, OB-cadherin and loss of RUNX2, and validated genomic alterations or increased expression at the DNA and RNA level in an independent cohort of 45 men with bone-metastatic CRPC and in 150 metastatic biopsies from men with mCRPC. Radium-223 was shown to reduce bone pain in patients with painful metastases secondary to prostate carcinoma with up to 70 of patients experiencing. We found evidence of persistent Cellsearch CTCs and B-ALP (+) CTCs in the majority of men over time during radium-223 therapy despite serum B-ALP normalization. We observed greater radium-223 radioactivity levels in metastatic bone tumor containing biopsies compared with adjacent normal bone. Xofigo (radium Ra 223 dichloride) is a radiotherapeutic drug used to treat patients with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease. RESULTS: We enrolled 20 men with symptomatic bone predominant mCRPC and treated with radium-223. We validated genomic findings in a separate independent study of men with bone metastatic mCRPC (n = 45) and publicly accessible data of metastatic CRPC tissues. We measured radium-223 decay products in tumor and surrounding normal bone during treatment. The primary objective was to describe the impact of radium-223 on the prevalence of CTC B-ALP over time. Prior to and three and six months after radium-223 treatment initiation, we collected CTCs and metastatic biopsies for phenotypic characterization and CTC genomic analysis. METHODS: We conducted a pharmacodynamic study (NCT02204943) of radium-223 in men with bone mCRPC. We hypothesized that osteomimicry, a form of epithelial plasticity leading to an osteoblastic phenotype, may contribute to intralesional deposition of radium-223 and subsequent irradiation of the tumor microenvironment. Updated analysis of the phase III, double-blind, randomized, multinational study of radium-223 chloride in castration-resistant prostate cancer with bone metastases (ALSYMPCA).BACKGROUND: Radium-223 is a targeted alpha-particle therapy that improves survival in men with metastatic castration resistant prostate cancer (mCRPC), particularly in men with elevated serum levels of bone alkaline phosphatase (B-ALP). The drug is marketed by Bayer Pharmaceuticals. The most common abnormalities detected in blood tests included anemia, lymphocytopenia, leukopenia, thrombocytopenia, and neutropenia. The most common side effects reported during clinical trials were nausea, diarrhea, vomiting and swelling of the leg, ankle, or foot, according to the FDA. The time to the first skeletal-related event was a median of 15.6 months in the radium-223 arm of the study, a significant prolongation over the 9.8 months in the placebo arm (HR = 0.658 95% CI, 0.522-0.830 P =. Although all isotopes of radium are radioactive, radium-223 has several properties that make it ideal for use as an anticancer agent. “Xofigo binds with minerals in the bone to deliver radiation directly to bone tumors, limiting the damage to the surrounding normal tissues,” Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a statement.Īccording to updated results presented at the 2012 American Society of Clinical Oncology (ASCO) Annual Meeting, radium-223 significantly improved overall survival (OS), with patients in the radium-223 arm of the study experiencing a median OS of 14.9 months compared with 11.3 months in the placebo arm (hazard ratio = 0.695 95% CI, 0.581-0.832 P =. The trial was designed to compare radium-223 with a placebo and best standard care in patients with CRPC and at least two bone metastases. The approval was based on results from the phase III, double-blind, randomized, multinational ALSYMPCA trial. Radium-223 is an injectable therapeutic alpha particle-emitting drug designed to have an antitumor effect on bone metastases in patients with mCRPC. Radium Ra 223 dichloride is a radiotherapeutic medication that emits alpha particles. The FDA approved the drug three months ahead of schedule through its expedited priority review program. The alpha radiation-emitting drug, known as radium-223 and formerly known as Alpharadin, was granted priority review in February. Radium RA 223 dichloride (Xofigo) has been approved by the FDA for the treatment of symptomatic metastatic castration-resistant prostate cancer (mCRPC) that has spread to the bones but not to any other organs.
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