{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T14:49:34Z","timestamp":1792162174493,"version":"4.4.0"},"reference-count":12,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2019,8,23]],"date-time":"2019-08-23T00:00:00Z","timestamp":1566518400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004326","name":"Bayer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004326","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Radium\u2010223 dichloride (radium\u2010223) is approved for patients with castration\u2010resistant prostate cancer (CRPC), symptomatic bone metastases, and no visceral disease using a dosing regimen of 6 injections (55\u2009kBq\/kg intravenously; 1 injection every 4 weeks). Early results from international, open\u2010label, phase 1\/2 study NCT01934790 showed that re\u2010treatment with radium\u2010223 was well tolerated with favorable effects on disease progression. Here we report safety and efficacy findings from 2\u2010year follow\u2010up of the radium\u2010223 re\u2010treatment study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients with CRPC and bone metastases who completed 6 initial radium\u2010223 injections with no disease progression in bone and later progressed were eligible for radium\u2010223 re\u2010treatment (up to 6 additional radium\u2010223 injections), provided that hematologic parameters were adequate and chemotherapy had not been administered after the initial course of radium\u2010223. Concomitant cytotoxic agents were not allowed during re\u2010treatment but were allowed at the investigator's discretion during follow\u2010up; other concomitant agents for prostate cancer (including abiraterone acetate or enzalutamide) were allowed at investigator's discretion. The primary objective was safety. Exploratory objectives included time to radiographic bone progression, radiographic progression\u2010free survival (rPFS), time to total alkaline phosphatase (tALP), and prostate\u2010specific antigen (PSA) progression, overall survival (OS), time to first symptomatic skeletal event (SSE), and SSE\u2010free survival, all calculated from re\u2010treatment start. Evaluation of safety and exploratory efficacy objectives included active 2\u2010year follow\u2010up. Safety results from active follow\u2010up and updated efficacy are reported.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Overall, 44 patients were re\u2010treated with radium\u2010223; 29 (66%) completed all 6 injections, and 34 (77%) entered 2\u2010year active follow\u2010up, during which no new safety concerns and no serious drug\u2010related adverse events were noted. rPFS events (progression or death) occurred in 19 (43%) of 44 patients; median rPFS was 9.9 months. Radiographic bone progression occurred in 5 (11%) of 44 patients. Median OS was 24.4 months. Median times to first SSE and SSE\u2010free survival were 16.7 and 12.8 months, respectively. Median time to tALP progression was not reached; median time to PSA progression was 2.2 months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Re\u2010treatment with radium\u2010223 in this selected patient population was well tolerated, led to minimal hematologic toxicity, and provided continued disease control in bone at 2\u2010year follow\u2010up.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.23893","type":"journal-article","created":{"date-parts":[[2019,8,23]],"date-time":"2019-08-23T16:18:49Z","timestamp":1566577129000},"page":"1683-1691","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Re\u2010treatment with radium\u2010223: 2\u2010year follow\u2010up from an international, open\u2010label, phase 1\/2 study in patients with castration\u2010resistant prostate cancer and bone metastases"],"prefix":"10.1002","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8777-7343","authenticated-orcid":false,"given":"Oliver","family":"Sartor","sequence":"first","affiliation":[{"name":"Departments of Medicine and Urology Tulane Cancer Center  New Orleans Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Heinrich","sequence":"additional","affiliation":[{"name":"Department of Oncology Akershus University Hospital  L\u00f8renskog Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Mariados","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Associated Medical Professionals of New York, PLLC  Syracuse New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Jos\u00e9","family":"M\u00e9ndez Vidal","sequence":"additional","affiliation":[{"name":"Oncology Department, Maimonides Institute of Biomedical Research (IMIBIC), Reina So\ufb01a Hospital University of Cordoba  Cordoba Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Keizman","sequence":"additional","affiliation":[{"name":"Genitourinary Oncology Unit, Meir Medical Center, Kfar\u2010Saba, and Sackler School of Medicine Tel\u00a0Aviv University  Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Thellenberg Karlsson","sequence":"additional","affiliation":[{"name":"Department of Radiation Sciences Cancer Center Norrlands University  Ume\u00e5 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avivit","family":"Peer","sequence":"additional","affiliation":[{"name":"Division of Oncology Rambam Health Care Campus  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Procopio","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology Fondazione Istituto Nazionale Tumori Oncologia Medica Genitourinaria  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Frank","sequence":"additional","affiliation":[{"name":"Department of Oncology Hadassah Hebrew University Medical Center  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalevi","family":"Pulkkanen","sequence":"additional","affiliation":[{"name":"Department of Oncology Kuopio University Hospital  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eli","family":"Rosenbaum","sequence":"additional","affiliation":[{"name":"Uro\u2010Oncology Unit Rabin Medical Center, Davidoff Center  Petah Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Severi","sequence":"additional","affiliation":[{"name":"Nuclear Medicine Therapeutic Unit, Romagnolo Scienti\ufb01c Institute for the Study and Care of Cancer, IRST IRCCS  Meldola Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Trigo","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Hospital Universitario Virgen de la Victoria  M\u00e1laga Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Trandafir","sequence":"additional","affiliation":[{"name":"Global Clinical Development, Bayer Pharma AG  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker","family":"Wagner","sequence":"additional","affiliation":[{"name":"Global Clinical Development, Bayer Pharma AG  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Li","sequence":"additional","affiliation":[{"name":"Global Research and Development Statistics, Bayer HealthCare Pharmaceuticals  Whippany New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke T.","family":"Nordquist","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology GU Research Network, LLC  Omaha Nebraska"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,8,23]]},"reference":[{"key":"e_1_2_8_1_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1213755"},{"key":"e_1_2_8_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)70183-4"},{"key":"e_1_2_8_1_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdw065"},{"key":"e_1_2_8_1_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clgc.2016.07.027"},{"key":"e_1_2_8_1_6_1","unstructured":"Xo\ufb01go (radium Ra 223 dichloride) injection for intravenous use [package insert]. Wayne NJ: Bayer HealthCare Pharmaceuticals Inc; May 2013.http:\/\/hcp.xofigo\u2010us.com\/index.php. Accessed 17 October 2018."},{"key":"e_1_2_8_1_7_1","doi-asserted-by":"publisher","DOI":"10.6028\/jres.120.004"},{"key":"e_1_2_8_1_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx044"},{"key":"e_1_2_8_1_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx331"},{"key":"e_1_2_8_1_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2018.09.040"},{"key":"e_1_2_8_1_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clgc.2016.09.001"},{"key":"e_1_2_8_1_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clgc.2017.11.009"},{"key":"e_1_2_8_1_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2015.11.022"}],"container-title":["The Prostate"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pros.23893","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pros.23893","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pros.23893","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T05:38:04Z","timestamp":1694324284000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pros.23893"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,23]]},"references-count":12,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2019,10]]}},"alternative-id":["10.1002\/pros.23893"],"URL":"https:\/\/doi.org\/10.1002\/pros.23893","archive":["Portico"],"relation":{},"ISSN":["0270-4137","1097-0045"],"issn-type":[{"value":"0270-4137","type":"print"},{"value":"1097-0045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,23]]},"assertion":[{"value":"2019-04-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-08-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}