title: Tandem dosing of samarium-153 ethylenediamine tetramethylene phosphoric acid with stem cell support for patients with high-risk osteosarcoma.
abstract: BACKGROUND
  Samarium-153 ethylenediamine tetramethylene phosphoric acid (153Sm-EDTMP) is a radiopharmaceutical that has been used to treat osteosarcoma. The authors conducted a phase 2 study to test safety and response of high-risk osteosarcoma to tandem doses of 153Sm-EDTMP and to determine correlation between radiation delivered by low and high administered activities.
  
  
  METHODS
  Patients with recurrent, refractory osteosarcoma detectable on standard 99mTc bone scan received a low dose of 153Sm-EDTMP (37.0-51.8 MBq/kg), followed upon count recovery by a second, higher dose (222 MBq/kg). Fourteen days later, patients were rescued with autologous hematopoietic stem cells. The authors assessed response to therapy, performed dosimetry to determine the relationship between administered activity and tumor absorbed dose, and investigated whether changes in 2-(fluorine-18) fluoro-2-deoxy-d-glucose (18F-FDG) tumor uptake upon hematologic recovery reflected disease response.
  
  
  RESULTS
  Nine patients were given tandem doses of 153Sm-EDTMP; 2 received only the initial dose because of disease progression. Six patients experienced radiographic disease stabilization, but this was not considered a response, so the study was terminated early. There was a linear relationship between administered activity and tumor absorbed dose, but there was no correlation between change in 18F-FDG positron emission tomography tumor uptake and tumor absorbed dose or time to progression. The median time to progression for the entire group was 79 days.
  
  
  CONCLUSIONS
  Tandem doses of 153Sm-EDTMP were safe for this cohort of heavily pretreated patients with very high-risk disease. The strong correlation between absorbed dose and administered activity within each evaluable patient provides a methodology to individually tailor tandem doses of this agent.
authors: Division of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland 21231, USA. loebda@jhmi.edu
authors: David M
authors: DM
authors: Loeb
authors: Robert F
authors: RF
authors: Hobbs
authors: Amarachukwu
authors: A
authors: Okoli
authors: Allen R
authors: AR
authors: Chen
authors: Steve
authors: S
authors: Cho
authors: Senthamizhchelvan
authors: S
authors: Srinivasan
authors: George
authors: G
authors: Sgouros
authors: Ori
authors: O
authors: Shokek
authors: Moody D
authors: MD
authors: Wharam
authors: Tammy
authors: T
authors: Scott
authors: Cindy L
authors: CL
authors: Schwartz
mesh_terms: D000293:Adolescent; D000328:Adult; D001859:Bone Neoplasms / Q000532:radiotherapy* / Q000601:surgery*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008297:Male; D009942:Organometallic Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D009943:Organophosphorus Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D012516:Osteosarcoma / Q000532:radiotherapy* / Q000601:surgery*; D011874:Radiometry; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000627:therapeutic use*; D014182:Transplantation, Autologous
chemical_list: D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; D019275:Radiopharmaceuticals; C061972:samarium Sm-153 lexidronam