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Anderson, P.M. et al.

Anderson, Wiseman, Dispenzieri, Arndt, Hartmann, Smithson, Mullan, Bruland,

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 ((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.[1]

References

High-dose samarium-153 ethylene diamine tetramethylene phosphonate: low toxicity of skeletal irradiation in patients with osteosarcoma and bone metastases. Anderson, P.M., Wiseman, G.A., Dispenzieri, A., Arndt, C.A., Hartmann, L.C., Smithson, W.A., Mullan, B.P., Bruland, O.S. J. Clin. Oncol. (2002) [Pubmed]

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