PMID- 32475774 OWN - NLM STAT- MEDLINE DCOM- 20210818 LR - 20210818 IS - 1938-0682 (Electronic) IS - 1558-7673 (Linking) VI - 18 IP - 5 DP - 2020 Oct TI - Open Label Phase II Study of Enzalutamide With Concurrent Administration of Radium 223 Dichloride in Patients With Castration-Resistant Prostate Cancer. PG - 416-422 LID - S1558-7673(20)30074-4 [pii] LID - 10.1016/j.clgc.2020.02.015 [doi] AB - BACKGROUND: Numerous globally approved castration-resistant prostate cancer (CRPC) therapies are available. Enzalutamide and radium 223 (Ra 223) are approved for survival prolongation and ability to delay radiographic progression. Both have markedly different mechanisms of action as well as safety and tolerability profiles. We prospectively investigated their combined safety and tolerability. PATIENTS AND METHODS: EnzaRadiCate, a phase II investigator-initiated trial, enrolled subjects with metastatic CRPC from 4 United States uro-oncology research sites. Safety assessment included physical examination, Eastern Cooperative Oncology Group status, electrocardiogram results, laboratory values, opioid use, radiographic responses, and adverse events (AEs). Quality of life and pain were assessed using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) and the Brief Pain Inventory Short Form (BPI-SF) questionnaires. RESULTS: Thirty-nine subjects completed at least 2 cycles of Ra 223, and 34 (87%) completed all 6 cycles through and the EOT visit. Sixty-one treatment-related AEs were reported by 53.8% of subjects. The most frequent AEs were fatigue (25.6%), nausea (17.9%), and anemia (12.8%). Three subjects experienced non-treatment-related serious AEs. One subject was hospitalized for sepsis, and 2 deaths were attributed to disease progression. Fifteen (38.5%) subjects demonstrated radiographic progression, and 24 (61.5%) subjects had no radiographic progression. CONCLUSIONS: Safety and tolerability of combinatorial use of enzalutamide and Ra 223 were demonstrated. Subjects experienced improvements in quality of life and pain, without unexpected toxicities nor increases in falls, fractures, or deaths. Phase III combination trials of Ra 223 with novel oral hormonal agents are ongoing to further evaluate radiographic progression and overall survival benefit. CI - Copyright (c) 2020 Elsevier Inc. All rights reserved. FAU - Shore, Neal D AU - Shore ND AD - Carolina Urologic Research Center, Myrtle Beach, SC. Electronic address: nshore@gsuro.com. FAU - Schellhammer, Paul F AU - Schellhammer PF AD - Urology of Virginia, Virginia Beach, VA. FAU - Tutrone, Ronald F AU - Tutrone RF AD - Chesapeake Urology Research Associates, Towson, MD. FAU - Mariados, Neil F AU - Mariados NF AD - Associated Medical Professionals of NY, Syracuse, NY. FAU - Harrelson, Stacey S AU - Harrelson SS AD - Palmetto Research Associates, Myrtle Beach, SC. LA - eng PT - Clinical Trial, Phase II PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200418 PL - United States TA - Clin Genitourin Cancer JT - Clinical genitourinary cancer JID - 101260955 RN - 0 (Benzamides) RN - 0 (Nitriles) RN - 2010-15-3 (Phenylthiohydantoin) RN - 93T0T9GKNU (enzalutamide) RN - W90AYD6R3Q (Radium) SB - IM MH - Benzamides MH - Humans MH - Male MH - Nitriles MH - Phenylthiohydantoin/adverse effects MH - *Prostatic Neoplasms, Castration-Resistant/drug therapy MH - Quality of Life MH - *Radium/adverse effects OTO - NOTNLM OT - Bone metastase OT - Fractures OT - Metastatic castration-resistant prostate cancer OT - Pain OT - Quality of life EDAT- 2020/06/02 06:00 MHDA- 2021/08/19 06:00 CRDT- 2020/06/02 06:00 PHST- 2019/11/18 00:00 [received] PHST- 2020/01/16 00:00 [revised] PHST- 2020/02/02 00:00 [accepted] PHST- 2020/06/02 06:00 [pubmed] PHST- 2021/08/19 06:00 [medline] PHST- 2020/06/02 06:00 [entrez] AID - S1558-7673(20)30074-4 [pii] AID - 10.1016/j.clgc.2020.02.015 [doi] PST - ppublish SO - Clin Genitourin Cancer. 2020 Oct;18(5):416-422. doi: 10.1016/j.clgc.2020.02.015. Epub 2020 Apr 18.