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Dose-finding study of 153Sm-EDTMP in patients with poor-prognosis osteosarcoma
Version of Record online: 31 MAR 2009
Copyright © 2009 American Cancer Society
Volume 115, Issue 11, pages 2514–2522, 1 June 2009
How to Cite
Loeb, D. M., Garrett-Mayer, E., Hobbs, R. F., Prideaux, A. R., Sgouros, G., Shokek, O., Wharam, M. D., Scott, T. and Schwartz, C. L. (2009), Dose-finding study of 153Sm-EDTMP in patients with poor-prognosis osteosarcoma. Cancer, 115: 2514–2522. doi: 10.1002/cncr.24286
- Issue online: 20 MAY 2009
- Version of Record online: 31 MAR 2009
- Manuscript Accepted: 24 NOV 2008
- Manuscript Revised: 30 OCT 2008
- Manuscript Received: 8 SEP 2008
- EUSA Pharma (USA) Inc (Formerly Cytogen Corp.)
- targeted radiotherapy;
- bone neoplasm
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.
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.
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.
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. Cancer 2009. © 2009 American Cancer Society.