title: Chemotherapy following radium-223 dichloride treatment in ALSYMPCA.
abstract: Radium-223 prolongs overall survival in patients with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases, regardless of prior docetaxel. Whether or not chemotherapy can be safely administered following radium-223 treatment is of clinical importance. An exploratory analysis of prospectively collected data, from the ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) patient subgroup who received chemotherapy after radium-223 or placebo treatment, was conducted to evaluate the safety and efficacy of chemotherapy following radium-223.
  
  
  
  In ALSYMPCA, CRPC patients with symptomatic bone metastases and no visceral metastases were randomized 2:1 to receive six injections of radium-223 (50 kBq/kg IV) or placebo plus best standard of care, stratified by prior docetaxel, baseline alkaline phosphatase, and current bisphosphonate use. In this exploratory analysis, chemotherapy agents administered following study treatment were identified; timing and duration were calculated. Hematologic safety was reviewed, and overall survival analyzed.
  
  
  
  Overall, 142 radium-223 and 64 placebo patients received subsequent chemotherapy; most common were docetaxel (70% radium-223, 72% placebo) and mitoxantrone (16% radium-223, 20% placebo). The majority of patients (61% radium-223, 58% placebo) had received prior docetaxel. Radium-223 patients started subsequent chemotherapy later than placebo patients; chemotherapy duration was similar between groups. In radium-223 and placebo patients receiving subsequent chemotherapy, median hematologic values (hemoglobin, neutrophils, and platelets) remained nearly constant up to 18 months following start of chemotherapy, regardless of prior docetaxel treatment. A low percentage of patients in both groups had grades 3-4 hematologic values (<10%). Platelet count decline, from last measurement before chemotherapy, was numerically greater in radium-223 versus placebo patients. Median overall survivals from start of chemotherapy were 16.0 and 15.8 months following radium-223 and placebo, respectively.
  
  
  
  Chemotherapy following radium-223, regardless of prior docetaxel, is feasible and appears to be well tolerated in patients with CRPC and symptomatic bone metastases. Prostate 76:905-916, 2016. © 2016 The Authors. The Prostate published by Wiley Periodicals, Inc.
authors.affiliation: Department of Medicine, Tulane Cancer Center, New Orleans, Louisiana.|Department of Urology, Tulane Cancer Center, New Orleans, Louisiana.
authors.forename: Oliver
authors.initials: O
authors.lastname: Sartor
authors.affiliation: Marie Curie Research Wing for Oncology, Mount Vernon Hospital Cancer Centre, Middlesex, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Hoskin
authors.affiliation: Academic Unit of Clinical Oncology, Weston Park Hospital, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Coleman
authors.affiliation: Department of Oncology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Sten
authors.initials: S
authors.lastname: Nilsson
authors.affiliation: Department of Medical Oncology, University of Nevada School of Medicine and Comprehensive Cancer Centers of Nevada, Las Vegas, Nevada.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Vogelzang
authors.affiliation: Department of Global Clinical Development, Bayer HealthCare Pharmaceuticals, Whippany, New Jersey.
authors.forename: Oana
authors.initials: O
authors.lastname: Petrenciuc
authors.affiliation: Department of Study Management Europe, Bayer AS (formerly Algeta ASA), Oslo, Norway.
authors.forename: Karin
authors.initials: K
authors.lastname: Staudacher
authors.affiliation: Department of Biostatistics, Statisticon AB, Uppsala, Sweden.
authors.forename: Marcus
authors.initials: M
authors.lastname: Thuresson
authors.affiliation: Academic Urology Unit, The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Sutton, Surrey, United Kingdom.
authors.forename: Christopher
authors.initials: C
authors.lastname: Parker
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000556:secondary; D003131:Combined Modality Therapy; D000077143:Docetaxel; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D064129:Prostatic Neoplasms, Castration-Resistant / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D011868:Radioisotopes / Q000627:therapeutic use; D011883:Radium / Q000627:therapeutic use*; D015996:Survival Rate; D043823:Taxoids / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D010919:Placebos; D011868:Radioisotopes; D043823:Taxoids; D000077143:Docetaxel; C581106:radium Ra 223 dichloride; D011883:Radium
keywords: alpha emitter; bone; chemotherapy; prostate; radium-223; safety