Tandem dosing of samarium-153 ethylenediamine tetramethylene phosphoric acid with stem cell support for patients with high-risk osteosarcoma

Background: Samarium-153 ethylenediamine tetramethylene phosphoric acid (¹⁵³Sm-EDTMP) is a radiopharmaceutical that has been used to treat osteosarcoma. The authors conducted a phase 2 study to test safety and response of high-risk osteosarcoma to tandem doses of ¹⁵³Sm-EDTMP and to determine correlation between radiation delivered by low and high administered activities. Methods: Patients with recurrent, refractory osteosarcoma detectable on standard ^99mTc bone scan received a low dose of ¹⁵³Sm-EDTMP (37.0-51.8 MBq/kg), followed upon count recovery by a second, higher dose (222 MBq/kg). Fourteen days later, patients were rescued with autologous hematopoietic stem cells. The authors assessed response to therapy, performed dosimetry to determine the relationship between administered activity and tumor absorbed dose, and investigated whether changes in 2-(fluorine-18) fluoro-2-deoxy-d-glucose (¹⁸F-FDG) tumor uptake upon hematologic recovery reflected disease response. Results: Nine patients were given tandem doses of ¹⁵³Sm-EDTMP; 2 received only the initial dose because of disease progression. Six patients experienced radiographic disease stabilization, but this was not considered a response, so the study was terminated early. There was a linear relationship between administered activity and tumor absorbed dose, but there was no correlation between change in ¹⁸F-FDG positron emission tomography tumor uptake and tumor absorbed dose or time to progression. The median time to progression for the entire group was 79 days. Conclusions: Tandem doses of ¹⁵³Sm-EDTMP were safe for this cohort of heavily pretreated patients with very high-risk disease. The strong correlation between absorbed dose and administered activity within each evaluable patient provides a methodology to individually tailor tandem doses of this agent. Cancer 2010. © 2010 American Cancer Society. Tandem doses of samarium-153 ethylenediamine tetramethylene phosphoric acid can be safely administered to heavily pretreated patients with high-risk osteosarcoma. There is a linear relationship between administered activity and tumor absorbed dose within each evaluable patient.