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

David M. Loeb, Robert F. Hobbs, Amarachukwu Okoli, Allen R. Chen, Steve Cho, Senthamizhchelvan Srinivasan, George Sgouros, Ori Shokek, Moody D. Wharam, Tammy Scott, Cindy L. Schwartz

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5470-5478
Number of pages9
JournalCancer
Volume116
Issue number23
DOIs
StatePublished - Dec 1 2010
Externally publishedYes

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ethylenediamine
Samarium
Osteosarcoma
Stem Cells
Neoplasms
Fluorodeoxyglucose F18
Radiopharmaceuticals
Fluorine
phosphoric acid
Hematopoietic Stem Cells

Keywords

  • bone neoplasm
  • osteosarcoma
  • radiopharmaceuticals
  • targeted radiotherapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Tandem dosing of samarium-153 ethylenediamine tetramethylene phosphoric acid with stem cell support for patients with high-risk osteosarcoma. / Loeb, David M.; Hobbs, Robert F.; Okoli, Amarachukwu; Chen, Allen R.; Cho, Steve; Srinivasan, Senthamizhchelvan; Sgouros, George; Shokek, Ori; Wharam, Moody D.; Scott, Tammy; Schwartz, Cindy L.

In: Cancer, Vol. 116, No. 23, 01.12.2010, p. 5470-5478.

Research output: Contribution to journalArticle

Loeb, DM, Hobbs, RF, Okoli, A, Chen, AR, Cho, S, Srinivasan, S, Sgouros, G, Shokek, O, Wharam, MD, Scott, T & Schwartz, CL 2010, 'Tandem dosing of samarium-153 ethylenediamine tetramethylene phosphoric acid with stem cell support for patients with high-risk osteosarcoma', Cancer, vol. 116, no. 23, pp. 5470-5478. https://doi.org/10.1002/cncr.25518
Loeb, David M. ; Hobbs, Robert F. ; Okoli, Amarachukwu ; Chen, Allen R. ; Cho, Steve ; Srinivasan, Senthamizhchelvan ; Sgouros, George ; Shokek, Ori ; Wharam, Moody D. ; Scott, Tammy ; Schwartz, Cindy L. / Tandem dosing of samarium-153 ethylenediamine tetramethylene phosphoric acid with stem cell support for patients with high-risk osteosarcoma. In: Cancer. 2010 ; Vol. 116, No. 23. pp. 5470-5478.
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abstract = "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. {\circledC} 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.",
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author = "Loeb, {David M.} and Hobbs, {Robert F.} and Amarachukwu Okoli and Chen, {Allen R.} and Steve Cho and Senthamizhchelvan Srinivasan and George Sgouros and Ori Shokek and Wharam, {Moody D.} and Tammy Scott and Schwartz, {Cindy L.}",
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T1 - Tandem dosing of samarium-153 ethylenediamine tetramethylene phosphoric acid with stem cell support for patients with high-risk osteosarcoma

AU - Loeb, David M.

AU - Hobbs, Robert F.

AU - Okoli, Amarachukwu

AU - Chen, Allen R.

AU - Cho, Steve

AU - Srinivasan, Senthamizhchelvan

AU - Sgouros, George

AU - Shokek, Ori

AU - Wharam, Moody D.

AU - Scott, Tammy

AU - Schwartz, Cindy L.

PY - 2010/12/1

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N2 - 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.

AB - 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.

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KW - osteosarcoma

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