Dose-finding study of 153Sm-EDTMP in patients with poor-prognosis osteosarcoma

David M. Loeb, Elizabeth Garrett-Mayer, Robert F. Hobbs, Andrew R. Prideaux, George Sgouros, Ori Shokek, Moody D. Wharam, Tammy Scott, Cindy L. Schwartz

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

BACKGROUND: Samarium-153 ethylenediaminetetramethylene phosphonic acid (153Sm-EDTMP) has been used to treat patients with high-risk osteosarcoma. The purpose of the current study was to determine the maximally tolerated dose of 153Sm-EDTMP that permits hematopoietic recovery within 6 weeks. METHODS: Patients with recurrent or refractory osteosarcoma with bone metastases were enrolled in this study. Subjects were treated with increasing doses of 153Sm-EDTMP, beginning with 1.0 millicuries (mCi)/kg and followed initially with 40% increment dose level escalations, using a continual reassessment method for dose escalation and de-escalation with a target dose-limiting toxicity (DLT) rate of 30%. Complete blood counts were monitored weekly, and the primary DLT was defined as failure to achieve an absolute neutrophil count >750/mm3 and a platelet count >75,000/mm3 within 6 weeks of treatment. In addition to assessing toxicity, dosimetry measurements were made to estimate the radiation dose delivered to target lesions. RESULTS: The maximally tolerated dose of 153Sm-EDTMP was 44.8 megabecquerel (MBq)/kg (1.21 mCi/kg). DLTs were confined to hematologic toxicities, particularly delayed platelet recovery in 2 patients treated at a dose of 51.8 MBq/kg (1.4 mCi/kg). Grade 2 and 3 pulmonary toxicity (graded according to the National Cancer Institute Common Toxicity Criteria [version 3.0]) as reported in 2 patients (at administered activities of 44.8 MBq/kg and 51.8 MBq/kg) was attributable to progressive pulmonary disease. No other significant nonhematologic toxicities were observed. CONCLUSIONS: Patients with osteosarcoma who have previously been heavily treated with chemotherapy can be safely administered 153Sm-EDTMP with rapid hematologic recovery. The data from the current study support the development of a future trial to assess the efficacy of combining targeted radiotherapy with cytotoxic chemotherapy as a treatment option for patients with high-risk osteosarcoma.

Original languageEnglish (US)
Pages (from-to)2514-2522
Number of pages9
JournalCancer
Volume115
Issue number11
DOIs
StatePublished - Jun 1 2009
Externally publishedYes

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Osteosarcoma
Maximum Tolerated Dose
Samarium
Drug Therapy
Blood Cell Count
National Cancer Institute (U.S.)
Platelet Count
Lung Diseases
samarium ethylenediaminetetramethylenephosphonate
Neutrophils
Radiotherapy
Blood Platelets
Radiation
Neoplasm Metastasis
Bone and Bones
Lung
Therapeutics

Keywords

  • Bone neoplasm
  • Osteosarcoma
  • Radiopharmaceuticals
  • Targeted radiotherapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Loeb, D. M., Garrett-Mayer, E., Hobbs, R. F., Prideaux, A. R., Sgouros, G., Shokek, O., ... Schwartz, C. L. (2009). Dose-finding study of 153Sm-EDTMP in patients with poor-prognosis osteosarcoma. Cancer, 115(11), 2514-2522. https://doi.org/10.1002/cncr.24286

Dose-finding study of 153Sm-EDTMP in patients with poor-prognosis osteosarcoma. / Loeb, David M.; Garrett-Mayer, Elizabeth; Hobbs, Robert F.; Prideaux, Andrew R.; Sgouros, George; Shokek, Ori; Wharam, Moody D.; Scott, Tammy; Schwartz, Cindy L.

In: Cancer, Vol. 115, No. 11, 01.06.2009, p. 2514-2522.

Research output: Contribution to journalArticle

Loeb, DM, Garrett-Mayer, E, Hobbs, RF, Prideaux, AR, Sgouros, G, Shokek, O, Wharam, MD, Scott, T & Schwartz, CL 2009, 'Dose-finding study of 153Sm-EDTMP in patients with poor-prognosis osteosarcoma', Cancer, vol. 115, no. 11, pp. 2514-2522. https://doi.org/10.1002/cncr.24286
Loeb DM, Garrett-Mayer E, Hobbs RF, Prideaux AR, Sgouros G, Shokek O et al. Dose-finding study of 153Sm-EDTMP in patients with poor-prognosis osteosarcoma. Cancer. 2009 Jun 1;115(11):2514-2522. https://doi.org/10.1002/cncr.24286
Loeb, David M. ; Garrett-Mayer, Elizabeth ; Hobbs, Robert F. ; Prideaux, Andrew R. ; Sgouros, George ; Shokek, Ori ; Wharam, Moody D. ; Scott, Tammy ; Schwartz, Cindy L. / Dose-finding study of 153Sm-EDTMP in patients with poor-prognosis osteosarcoma. In: Cancer. 2009 ; Vol. 115, No. 11. pp. 2514-2522.
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abstract = "BACKGROUND: Samarium-153 ethylenediaminetetramethylene phosphonic acid (153Sm-EDTMP) has been used to treat patients with high-risk osteosarcoma. The purpose of the current study was to determine the maximally tolerated dose of 153Sm-EDTMP that permits hematopoietic recovery within 6 weeks. METHODS: Patients with recurrent or refractory osteosarcoma with bone metastases were enrolled in this study. Subjects were treated with increasing doses of 153Sm-EDTMP, beginning with 1.0 millicuries (mCi)/kg and followed initially with 40{\%} increment dose level escalations, using a continual reassessment method for dose escalation and de-escalation with a target dose-limiting toxicity (DLT) rate of 30{\%}. Complete blood counts were monitored weekly, and the primary DLT was defined as failure to achieve an absolute neutrophil count >750/mm3 and a platelet count >75,000/mm3 within 6 weeks of treatment. In addition to assessing toxicity, dosimetry measurements were made to estimate the radiation dose delivered to target lesions. RESULTS: The maximally tolerated dose of 153Sm-EDTMP was 44.8 megabecquerel (MBq)/kg (1.21 mCi/kg). DLTs were confined to hematologic toxicities, particularly delayed platelet recovery in 2 patients treated at a dose of 51.8 MBq/kg (1.4 mCi/kg). Grade 2 and 3 pulmonary toxicity (graded according to the National Cancer Institute Common Toxicity Criteria [version 3.0]) as reported in 2 patients (at administered activities of 44.8 MBq/kg and 51.8 MBq/kg) was attributable to progressive pulmonary disease. No other significant nonhematologic toxicities were observed. CONCLUSIONS: Patients with osteosarcoma who have previously been heavily treated with chemotherapy can be safely administered 153Sm-EDTMP with rapid hematologic recovery. The data from the current study support the development of a future trial to assess the efficacy of combining targeted radiotherapy with cytotoxic chemotherapy as a treatment option for patients with high-risk osteosarcoma.",
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AU - Loeb, David M.

AU - Garrett-Mayer, Elizabeth

AU - Hobbs, Robert F.

AU - Prideaux, Andrew R.

AU - Sgouros, George

AU - Shokek, Ori

AU - Wharam, Moody D.

AU - Scott, Tammy

AU - Schwartz, Cindy L.

PY - 2009/6/1

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N2 - BACKGROUND: Samarium-153 ethylenediaminetetramethylene phosphonic acid (153Sm-EDTMP) has been used to treat patients with high-risk osteosarcoma. The purpose of the current study was to determine the maximally tolerated dose of 153Sm-EDTMP that permits hematopoietic recovery within 6 weeks. METHODS: Patients with recurrent or refractory osteosarcoma with bone metastases were enrolled in this study. Subjects were treated with increasing doses of 153Sm-EDTMP, beginning with 1.0 millicuries (mCi)/kg and followed initially with 40% increment dose level escalations, using a continual reassessment method for dose escalation and de-escalation with a target dose-limiting toxicity (DLT) rate of 30%. Complete blood counts were monitored weekly, and the primary DLT was defined as failure to achieve an absolute neutrophil count >750/mm3 and a platelet count >75,000/mm3 within 6 weeks of treatment. In addition to assessing toxicity, dosimetry measurements were made to estimate the radiation dose delivered to target lesions. RESULTS: The maximally tolerated dose of 153Sm-EDTMP was 44.8 megabecquerel (MBq)/kg (1.21 mCi/kg). DLTs were confined to hematologic toxicities, particularly delayed platelet recovery in 2 patients treated at a dose of 51.8 MBq/kg (1.4 mCi/kg). Grade 2 and 3 pulmonary toxicity (graded according to the National Cancer Institute Common Toxicity Criteria [version 3.0]) as reported in 2 patients (at administered activities of 44.8 MBq/kg and 51.8 MBq/kg) was attributable to progressive pulmonary disease. No other significant nonhematologic toxicities were observed. CONCLUSIONS: Patients with osteosarcoma who have previously been heavily treated with chemotherapy can be safely administered 153Sm-EDTMP with rapid hematologic recovery. The data from the current study support the development of a future trial to assess the efficacy of combining targeted radiotherapy with cytotoxic chemotherapy as a treatment option for patients with high-risk osteosarcoma.

AB - BACKGROUND: Samarium-153 ethylenediaminetetramethylene phosphonic acid (153Sm-EDTMP) has been used to treat patients with high-risk osteosarcoma. The purpose of the current study was to determine the maximally tolerated dose of 153Sm-EDTMP that permits hematopoietic recovery within 6 weeks. METHODS: Patients with recurrent or refractory osteosarcoma with bone metastases were enrolled in this study. Subjects were treated with increasing doses of 153Sm-EDTMP, beginning with 1.0 millicuries (mCi)/kg and followed initially with 40% increment dose level escalations, using a continual reassessment method for dose escalation and de-escalation with a target dose-limiting toxicity (DLT) rate of 30%. Complete blood counts were monitored weekly, and the primary DLT was defined as failure to achieve an absolute neutrophil count >750/mm3 and a platelet count >75,000/mm3 within 6 weeks of treatment. In addition to assessing toxicity, dosimetry measurements were made to estimate the radiation dose delivered to target lesions. RESULTS: The maximally tolerated dose of 153Sm-EDTMP was 44.8 megabecquerel (MBq)/kg (1.21 mCi/kg). DLTs were confined to hematologic toxicities, particularly delayed platelet recovery in 2 patients treated at a dose of 51.8 MBq/kg (1.4 mCi/kg). Grade 2 and 3 pulmonary toxicity (graded according to the National Cancer Institute Common Toxicity Criteria [version 3.0]) as reported in 2 patients (at administered activities of 44.8 MBq/kg and 51.8 MBq/kg) was attributable to progressive pulmonary disease. No other significant nonhematologic toxicities were observed. CONCLUSIONS: Patients with osteosarcoma who have previously been heavily treated with chemotherapy can be safely administered 153Sm-EDTMP with rapid hematologic recovery. The data from the current study support the development of a future trial to assess the efficacy of combining targeted radiotherapy with cytotoxic chemotherapy as a treatment option for patients with high-risk osteosarcoma.

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