title: Radiopharmaceuticals for Palliation of Bone Pain in Patients with Castration-resistant Prostate Cancer Metastatic to Bone: A Systematic Review.
abstract: The majority of patients with castration-resistant prostate cancer develop bone metastatic disease. It is often challenging to optimally palliate malignant bone pain. In case of multifocal pain due to diffuse osteoblastic metastases, treatment with bone-seeking radiopharmaceuticals can be considered.
  
  
  
  This systematic review evaluates the efficacy of different bone-seeking radiopharmaceuticals for palliation of malignant bone pain from prostate cancer.
  
  
  
  The PubMed (Medline) and Embase databases were searched for publications on 89-strontium-chloride ((89)Sr), 153-samarium-EDTMP ((153)Sm), 186-rhenium-HEDP ((186)Re), 188-rhenium-HEDP ((188)Re), and 223-radium-chloride ((223)Ra). Randomised controlled trials and prospective cohort studies were included. Metastatic bone pain had to be registered as outcome measure for prostate cancer patients separately.
  
  
  
  This review included 36 articles of which 13 randomised trials and 23 prospective studies. Of all trials, 10 studies used (89)Sr, 7 (153)Sm, 12 (186)Re, 2 (188)Re, and 2 (223)Ra; three reported on a combination of different radionuclides. Only a few trials contained a blinding procedure and several studies contained incomplete follow-up or lack of intention-to-treat analysis. It was not possible to calculate a pooled estimate of pain response to treatment with any of the radionuclides because different definitions of pain response were used.
  
  
  
  Overall, pain response percentages greater than 50-60% were seen with each radionuclide. Haematological toxicity was reported in 26 of the 36 studies and more than half of these trials stated no grade 3/4 leukopenia or thrombocytopenia occurred.
  
  
  
  In this report we reviewed the efficacy of bone-seeking radionuclides for treating bone pain from metastatic prostate cancer. Overall, treatment with bone-seeking radionuclides resulted in pain responses greater than 50-60%.
authors.affiliation: Department of Medical Oncology, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Joyce M van Dodewaard-de
authors.initials: JM
authors.lastname: Jong
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Daniela E
authors.initials: DE
authors.lastname: Oprea-Lager
authors.affiliation: Dutch Cochrane Centre Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Lotty
authors.initials: L
authors.lastname: Hooft
authors.affiliation: Department of Nuclear Medicine, Meander Medical Centre, Amersfoort, The Netherlands.
authors.forename: John M H
authors.initials: JM
authors.lastname: de Klerk
authors.affiliation: Department of Medical Oncology, Meander Medical Centre, Amersfoort, The Netherlands.
authors.forename: Haiko J
authors.initials: HJ
authors.lastname: Bloemendal
authors.affiliation: Department of Medical Oncology, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Henk M W
authors.initials: HM
authors.lastname: Verheul
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Otto S
authors.initials: OS
authors.lastname: Hoekstra
authors.affiliation: Department of Medical Oncology, VU University Medical Centre, Amsterdam, The Netherlands. Electronic address: vandeneertwegh@vumc.nl.
authors.forename: Alfons J M
authors.initials: AJ
authors.lastname: van den Eertwegh
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000556:secondary; D000072716:Cancer Pain / Q000188:drug therapy* / Q000209:etiology; D012968:Etidronic Acid / Q000627:therapeutic use; D006801:Humans; D008297:Male; D009942:Organometallic Compounds / Q000627:therapeutic use; D009943:Organophosphorus Compounds / Q000627:therapeutic use; D010166:Palliative Care / Q000379:methods*; D011446:Prospective Studies; D064129:Prostatic Neoplasms, Castration-Resistant / Q000473:pathology*; D011868:Radioisotopes / Q000627:therapeutic use; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000627:therapeutic use*; D011883:Radium / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D013324:Strontium / Q000627:therapeutic use; D013326:Strontium Radioisotopes / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D013326:Strontium Radioisotopes; C101598:rhenium-186 HEDP; C061972:samarium Sm-153 lexidronam; C025700:strontium chloride; D012968:Etidronic Acid; C581106:radium Ra 223 dichloride; D011883:Radium; D013324:Strontium
keywords: Bone metastases; Bone pain; Bone seeking radiopharmaceutical; Prostate cancer