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High-Dose Samarium-153 Ethylene Diamine Tetramethylene Phosphonate: Low Toxicity of Skeletal Irradiation in Patients With Osteosarcoma and Bone Metastases

University of Münster, Münster, Germany

To the Editor:Targeted radiotherapy with high-dose samarium-153 ethylene diamine tetramethylene phosphonate (¹⁵³Sm-EDTMP), as reported by Anderson et al¹ in the January 1, 2002, issue of the Journal of Clinical Oncology, comes as a welcome addition to the limited therapeutic armamentarium available against inoperable osteosarcoma. The authors are to be commended for demonstrating that the standard activity of ¹⁵³Sm-EDTMP can be increased up to 30-fold with peripheral-blood progenitor cell support, thereby allowing the delivery of substantial radiation doses to osteoblastic lesions. In their article, Anderson et al state that, so far, there are no reports of ¹⁵³Sm-EDTMP as primary treatment of osteosarcoma in humans. We would like to draw attention to the case of a 21-year-old female patient with a large pelvic osteosarcoma and multiple primary pulmonary metastases, which were histologically verified. Both the primary lesion and the metastases appeared "hot" on technetium-99m methylene diphosphonate bone scans and were clearly visible on [¹⁸F]-fluorodeoxyglucose positron emission tomography. Because neither tumor location was amenable to curative surgery, it was decided to treat the patient with high-activity ¹⁵³Sm-EDTMP (4.5 mCi/kg), peripheral-blood progenitor cell support, external-beam irradiation to the pelvic lesion (total dose, 60 Gy), and multiagent chemotherapy according to a modified COSS-96 regimen of the Cooperative Osteosarcoma Study Group. This treatment led to almost immediate pain relief, followed soon by a marked reduction of tracer uptake in both bone scan and [¹⁸F]-fluorodeoxyglucose positron emission tomography.² Currently, 3 years and 4 months after ¹⁵³Sm-EDTMP therapy, the patient is still alive and well without signs of active tumor. In contrast, not one of 15 prior Cooperative Osteosarcoma Study Group patients with pelvic osteosarcoma and proven primary dissemination who did not achieve a complete surgical remission of all known tumor sites survived; the median time to death in this group was only 1.2 years from diagnosis (range, 3.4 months to 3.0 years). Thus, aggressive, first-line therapy combining targeted internal radiotherapy with high-dose ¹⁵³Sm-EDTMP, external-beam irradiation, and multiagent chemotherapy may offer a reasonable treatment option for selected patients with inoperable osteosarcoma.³ Further studies aiming to define the exact role of this multimodal concept are warranted.

REFERENCES

1. Anderson PM, Wiseman GA, Dispenzeri A, et al: High-Dose samarium-153 ethylene diamine tetramethylene phosphonate: Low toxicity of skeletal irradiation in patients with osteosarcoma and bone metastases. J Clin Oncol 20: 189-196, 2002[Abstract/Free Full Text]

2. Franzius C, Bielack S, Sciuk J, et al: High-activity samarium-153-EDTMP therapy in unresectable osteosarcoma. Nuklearmedizin 38: 337-340, 1999[Medline]

3. Franzius C, Bielack S, Flege S, et al: High-activity samarium-153-EDTMP therapy followed by autologous peripheral blood stem cell support in unresectable osteosarcoma. Nuklearmedizin 40: 215-220, 2001[Medline]

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