High-dose samarium-153 ethylene diamine tetramethylene phosphonate: low toxicity of skeletal irradiation in patients with osteosarcoma and bone metastases

J Clin Oncol. 2002 Jan 1;20(1):189-96. doi: 10.1200/JCO.2002.20.1.189.


Purpose: Samarium-153 ethylene diamine tetramethylene phosphonate ((153)Sm-EDTMP), a bone-seeking radiopharmaceutical, provides therapeutic irradiation to osteoblastic bone metastases. Because the dose-limiting toxicity of (153)Sm-EDTMP is thrombocytopenia, a dose-escalation trial using peripheral-blood progenitor cells (PBPCs) or marrow support was conducted to treat metastatic bone cancer.

Patients and methods: Patients with locally recurrent or metastatic osteosarcoma or skeletal metastases avid on bone scan were treated with 1, 3, 4.5, 6, 12, 19, or 30 mCi/kg of (153)Sm-EDTMP.

Results: Thirty patients were treated with (153)Sm-EDTMP. Transient symptoms of hypocalcemia were seen at 30 mCi/kg. Estimates of radioisotope bound to bone surfaces and marrow radiation dose were linear with injected amount of (153)Sm-EDTMP. Cytopenias also occurred in all subjects and were dose-related. At day +13 after (153)Sm-EDTMP, residual whole-body radioactivity was 1% to 65% of whole-body radioactivity considered safe for PBPC infusion, 3.6 mCi. After PBPC or marrow infusion on day +14 after (153)Sm-EDTMP, recovery of hematopoiesis was problematic in two patients at the 30 mCi/kg dose infused with less than 2 x 10(6) CD34(+)/kg on day +14, but not in other patients. Reduction or elimination of opiates for pain was seen in all patients. Patients had no adverse changes in appetite or performance status.

Conclusion: (153)Sm-EDTMP with PBPC support can provide bone-specific therapeutic irradiation (estimates of 39 to 241 Gy). Hematologic toxicity at 30 mCi (153)Sm-EDTMP/kg requires PBPC grafts with more than 2 x 10(6) CD34(+)/kg to overcome myeloablative effects of skeletal irradiation. Nonhematologic side effects are minimal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Bone Neoplasms / radiotherapy*
  • Bone Neoplasms / secondary*
  • Child
  • Dose-Response Relationship, Drug
  • Hematologic Diseases / etiology
  • Hematologic Diseases / therapy
  • Humans
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Organometallic Compounds / adverse effects
  • Organometallic Compounds / therapeutic use*
  • Organophosphorus Compounds / adverse effects
  • Organophosphorus Compounds / therapeutic use*
  • Osteosarcoma / radiotherapy*
  • Osteosarcoma / secondary
  • Palliative Care / methods*
  • Radioisotopes / adverse effects
  • Radioisotopes / therapeutic use*
  • Samarium / adverse effects
  • Samarium / therapeutic use*
  • Tissue Distribution


  • Organometallic Compounds
  • Organophosphorus Compounds
  • Radioisotopes
  • Samarium
  • samarium Sm-153 lexidronam