title: First clinical experience with alpha-emitting radium-223 in the treatment of skeletal metastases.
abstract: OBJECTIVE
  The main goals were to study the safety and tolerability of the alpha-emitter radium-223 (223Ra) in breast and prostate cancer patients with skeletal metastases. In addition, pain palliation was evaluated.
  
  
  METHODS
  Fifteen prostate and 10 breast cancer patients enrolled in a phase I trial received a single i.v. injection of 223Ra. Five patients were included at each of the dosages: 46, 93, 163, 213, or 250 kBq/kg and followed for 8 weeks. Palliative response was evaluated according to the pain scale of the European Organization for Research and Treatment of Cancer QLQ C30 questionnaire at baseline and at 1, 4, and 8 weeks after injection.
  
  
  RESULTS
  Weekly blood sampling during follow-up revealed mild and reversible myelosuppression with nadir 2 to 4 weeks after the injection. Importantly, for thrombocytes only grade 1 toxicity was reported. Grade 3 neutropenia and leucopenia occurred in two and three patients, respectively. Mild, transient diarrhea was observed in 10 of the 25 patients. Nausea and vomiting was more frequently observed in the highest dosage group. Serum alkaline phosphatase decreased with nadir averages of 29.5% in females and 52.1% in males. Pain relief was reported by 52%, 60%, and 56% of the patients after 7 days, 4, and 8 weeks, respectively. 223Ra cleared rapidly from blood and was below 1% of initial level at 24 hours. Gamma camera images indicated, in accordance with pretreatment (99m)Tc-MDP scans, accumulation of 223Ra in skeletal lesions. Elimination was mainly intestinal. Median survival exceeded 20 months.
  
  
  CONCLUSIONS
  223Ra was well tolerated at therapeutically relevant dosages. Phase II studies have therefore been initiated.
authors.affiliation: Radiumhemmet, The Karolinska Hospital and Institute, Stockholm, Sweden.
authors.forename: Sten
authors.initials: S
authors.lastname: Nilsson
authors.forename: Roy H
authors.initials: RH
authors.lastname: Larsen
authors.forename: Sophie D
authors.initials: SD
authors.lastname: Fosså
authors.forename: Lise
authors.initials: L
authors.lastname: Balteskard
authors.forename: Kari W
authors.initials: KW
authors.lastname: Borch
authors.forename: Jan-Erik
authors.initials: JE
authors.lastname: Westlin
authors.forename: Gro
authors.initials: G
authors.lastname: Salberg
authors.forename: Oyvind S
authors.initials: OS
authors.lastname: Bruland
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000097:blood; D000512:Alpha Particles / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy* / Q000556:secondary; D001943:Breast Neoplasms / Q000473:pathology / Q000532:radiotherapy; D003967:Diarrhea / Q000209:etiology; D004307:Dose-Response Relationship, Radiation; D005221:Fatigue / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007275:Injections, Intravenous; D007970:Leukopenia / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000209:etiology; D009503:Neutropenia / Q000209:etiology; D010146:Pain / Q000209:etiology; D011471:Prostatic Neoplasms / Q000473:pathology / Q000532:radiotherapy; D011877:Radionuclide Imaging; D011883:Radium / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D016896:Treatment Outcome; D014839:Vomiting / Q000209:etiology
chemical_list: D000469:Alkaline Phosphatase; D011883:Radium