title: Dose-finding study of 153Sm-EDTMP in patients with poor-prognosis osteosarcoma.
abstract: BACKGROUND
  Samarium-153 ethylenediaminetetramethylene phosphonic acid ((153)Sm-EDTMP) has been used to treat patients with high-risk osteosarcoma. The purpose of the current study was to determine the maximally tolerated dose of (153)Sm-EDTMP that permits hematopoietic recovery within 6 weeks.
  
  
  METHODS
  Patients with recurrent or refractory osteosarcoma with bone metastases were enrolled in this study. Subjects were treated with increasing doses of (153)Sm-EDTMP, beginning with 1.0 millicuries (mCi)/kg and followed initially with 40% increment dose level escalations, using a continual reassessment method for dose escalation and de-escalation with a target dose-limiting toxicity (DLT) rate of 30%. Complete blood counts were monitored weekly, and the primary DLT was defined as failure to achieve an absolute neutrophil count >750/mm(3) and a platelet count >75,000/mm(3) within 6 weeks of treatment. In addition to assessing toxicity, dosimetry measurements were made to estimate the radiation dose delivered to target lesions.
  
  
  RESULTS
  The maximally tolerated dose of (153)Sm-EDTMP was 44.8 megabecquerel (MBq)/kg (1.21 mCi/kg). DLTs were confined to hematologic toxicities, particularly delayed platelet recovery in 2 patients treated at a dose of 51.8 MBq/kg (1.4 mCi/kg). Grade 2 and 3 pulmonary toxicity (graded according to the National Cancer Institute Common Toxicity Criteria [version 3.0]) as reported in 2 patients (at administered activities of 44.8 MBq/kg and 51.8 MBq/kg) was attributable to progressive pulmonary disease. No other significant nonhematologic toxicities were observed.
  
  
  CONCLUSIONS
  Patients with osteosarcoma who have previously been heavily treated with chemotherapy can be safely administered (153)Sm-EDTMP with rapid hematologic recovery. The data from the current study support the development of a future trial to assess the efficacy of combining targeted radiotherapy with cytotoxic chemotherapy as a treatment option for patients with high-risk osteosarcoma.
authors.affiliation: Division of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland 21231, USA. loebda@jhmi.edu
authors.forename: David M
authors.initials: DM
authors.lastname: Loeb
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Garrett-Mayer
authors.forename: Robert F
authors.initials: RF
authors.lastname: Hobbs
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Prideaux
authors.forename: George
authors.initials: G
authors.lastname: Sgouros
authors.forename: Ori
authors.initials: O
authors.lastname: Shokek
authors.forename: Moody D
authors.initials: MD
authors.lastname: Wharam
authors.forename: Tammy
authors.initials: T
authors.lastname: Scott
authors.forename: Cindy L
authors.initials: CL
authors.lastname: Schwartz