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

Abstract

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.

• Authors: Peter M Anderson, Gregory A Wiseman, Angela Dispenzieri, Carola A S Arndt, Lynn C Hartmann, William A Smithson, Brian P Mullan, Oyvind S Bruland
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 20 Issue 1 Pg. 189-96 (Jan 01 2002) ISSN: 0732-183X [Print] United States
• PMID: 11773169 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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