Shane McGann1, Evan R Horton2. 1. MCPHS University, Boston, MA, USA Genzyme, A Sanofi Company, Cambridge, MA, USA shane.mcgann@mcphs.edu. 2. MCPHS University, Boston, MA, USA.
Abstract
OBJECTIVE: To review and evaluate the clinical trial efficacy and safety of radium 223 ((223)Ra) along with its place in therapy in men with castration-resistant prostate cancer (CRPC). DATA SOURCES: A literature search in PubMed/MEDLINE (up to October 2014) was performed using various combinations of the terms radium, hormone-refractory prostate cancer, and castration-resistant prostate cancer. The New Drug Application Medical, Pharmacology, and Clinical Pharmacology and Biopharmaceutics Reviews for radium (223)Ra dichloride were also utilized. The bibliographies of articles were reviewed to identify additional references. STUDY SELECTION AND DATA EXTRACTION: Phase 1, 2, and 3 studies that assessed the safety and/or efficacy of (223)Ra in patients with CRPC were reviewed. Peer-reviewed articles with clinically relevant information were reviewed for background information. DATA SYNTHESIS: In May 2013, the Food and Drug Administration approved intravenous use of (223)Ra for the treatment of patients with CRPC, symptomatic bone metastases, and no known visceral metastatic disease. In a phase 3 study comparing (223)Ra and the best standard of care (SOC) versus the best SOC plus placebo, (223)Ra was shown to increase survival. The most commonly seen adverse drug reactions and hematological laboratory abnormalities with (223)Ra include nausea, diarrhea, vomiting, peripheral edema, anemia, lymphocytopenia, leukopenia, thrombocytopenia, and neutropenia. CONCLUSIONS: (223)Ra is a first-in-class α-particle-emitting radioactive agent that is first-line therapy, providing an extra option for men suffering from CRPC with symptomatic bone metastases and no known visceral metastases. (223)Ra has also been shown to be relatively well tolerated when up to 6 injections are given. Further studies are needed to evaluate whether (223)Ra is safe and effective for more than 6 doses and if it can be used concomitantly with chemotherapy.
OBJECTIVE: To review and evaluate the clinical trial efficacy and safety of radium 223 ((223)Ra) along with its place in therapy in men with castration-resistant prostate cancer (CRPC). DATA SOURCES: A literature search in PubMed/MEDLINE (up to October 2014) was performed using various combinations of the terms radium, hormone-refractory prostate cancer, and castration-resistant prostate cancer. The New Drug Application Medical, Pharmacology, and Clinical Pharmacology and Biopharmaceutics Reviews for radium (223)Ra dichloride were also utilized. The bibliographies of articles were reviewed to identify additional references. STUDY SELECTION AND DATA EXTRACTION: Phase 1, 2, and 3 studies that assessed the safety and/or efficacy of (223)Ra in patients with CRPC were reviewed. Peer-reviewed articles with clinically relevant information were reviewed for background information. DATA SYNTHESIS: In May 2013, the Food and Drug Administration approved intravenous use of (223)Ra for the treatment of patients with CRPC, symptomatic bone metastases, and no known visceral metastatic disease. In a phase 3 study comparing (223)Ra and the best standard of care (SOC) versus the best SOC plus placebo, (223)Ra was shown to increase survival. The most commonly seen adverse drug reactions and hematological laboratory abnormalities with (223)Ra include nausea, diarrhea, vomiting, peripheral edema, anemia, lymphocytopenia, leukopenia, thrombocytopenia, and neutropenia. CONCLUSIONS: (223)Ra is a first-in-class α-particle-emitting radioactive agent that is first-line therapy, providing an extra option for men suffering from CRPC with symptomatic bone metastases and no known visceral metastases. (223)Ra has also been shown to be relatively well tolerated when up to 6 injections are given. Further studies are needed to evaluate whether (223)Ra is safe and effective for more than 6 doses and if it can be used concomitantly with chemotherapy.
Keywords:
adult medicine; cancer; clinical decision making; drug development and approval; drug trials; education; oncology; radioisotopes; supportive care
Authors: Zs Küronya; I Sinkovics; P Ágoston; K Bíró; I Bodrogi; I Böde; M Dank; F Gyergyay; T Vajdics; Zs Kolonics; K Nagyiványi; Á Rúzsa; L Géczi Journal: Pathol Oncol Res Date: 2017-01-10 Impact factor: 3.201