High-Dose Samarium-153 Ethylene Diamine Tetramethylene Phosphonate: Low Toxicity of Skeletal Irradiation in Patients With Osteosarcoma and Bone Metastases

PURPOSE: Samarium-153 ethylene diamine tetramethylene phosphonate (153Sm-EDTMP), a bone-seeking radiopharmaceutical, provides therapeutic irradiation to osteoblastic bone metastases. Because the dose-limiting toxicity of 153Sm-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 153Sm-EDTMP. RESULTS: Thirty patients were treated with 153Sm-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 153Sm-EDTMP. Cytopenias also occurred in all subjects and were dose-related. At day +13 after 153Sm-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 153Sm-EDTMP, recovery of hematopoiesis was problematic in two patients at the 30 mCi/kg dose infused with less than 2 × 106 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: 153Sm-EDTMP with PBPC support can provide bone-specific therapeutic irradiation (estimates of 39 to 241 Gy). Hematologic toxicity at 30 mCi 153Sm-EDTMP/kg requires PBPC grafts with more than 2 × 106 CD34+/kg to overcome myeloablative effects of skeletal irradiation. Nonhematologic side effects are minimal.