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


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.


CONCLUSIONS
(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.
Anderson
Peter M
PM
Department of Pediatrics, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA. anderson.peter@mayo.edu
Wiseman
Gregory A
GA
Dispenzieri
Angela
A
Arndt
Carola A S
CA
Hartmann
Lynn C
LC
Smithson
William A
WA
Mullan
Brian P
BP
Bruland
Oyvind S
OS
D000293:Adolescent; D000328:Adult; D001859:Bone Neoplasms / Q000532:radiotherapy* / Q000556:secondary*; D002648:Child; D004305:Dose-Response Relationship, Drug; D006402:Hematologic Diseases / Q000209:etiology / Q000628:therapy; D006801:Humans; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009942:Organometallic Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D009943:Organophosphorus Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D012516:Osteosarcoma / Q000532:radiotherapy* / Q000556:secondary; D010166:Palliative Care / Q000379:methods*; D011868:Radioisotopes / Q000009:adverse effects / Q000627:therapeutic use*; D012493:Samarium / Q000009:adverse effects / Q000627:therapeutic use*; D014018:Tissue Distribution
D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; D011868:Radioisotopes; D012493:Samarium; C061972:samarium Sm-153 lexidronam