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Gemcitabine Radiosensitization after High-Dose Samarium for Osteoblastic Osteosarcoma

Authors' Affiliations: ¹ M.D. Anderson Cancer Center, Houston, Texas; ² Mayo Clinic, Rochester, Minnesota; ³ State University of New York Upstate Medical University, Syracuse, New York; and ⁴ Dana-Farber Cancer Institute, Boston, Massachusetts

Requests for reprints: Peter M. Anderson, Pediatrics, Unit 87, M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030-4009. Phone: 713-563-0893; Fax: 713-794-5042; E-mail: pmanders{at}mdanderson.org.

Osteoblastic metastases and osteosarcoma can avidly concentrate bone-seeking radiopharmaceuticals. We sought to increase effectiveness of high-dose ¹⁵³Samarium ethylenediaminetetramethylenephosphonate (¹⁵³Sm-EDTMP, Quadramet) on osteosarcomas using a radiosensitizer, gemcitabine. Fourteen patients with osteoblastic lesions were treated with 30 mCi/kg ¹⁵³Sm-EDTMP. Gemcitabine was administered 1 day after samarium infusion. Residual total body radioactivity was within the safe range of <3.6 mCi on day +14 (1.1 ± 0.4 mCi; range, 0.67-1.8 mCi). All patients received autologous stem cell reinfusion 2 weeks after ¹⁵³Sm to correct expected grade 4 hematopoietic toxicity. Peripheral blood progenitor cells were infused in 11 patients; three patients had marrow infused. Blood count recovery was uneventful after peripheral blood progenitor cells in 11 of 11 patients. Toxicity from a single infusion of gemcitabine (1,500 mg/m²) in combination with ¹⁵³Sm-EDTMP was minimal (pancytopenia). However, toxicity from a daily gemcitabine regimen (250 mg/m²/d x 4-5 days) was excessive (grade 3 mucositis) in one of two patients. There were no reported episodes of hemorrhagic cystitis (hematuria) or nephrotoxicity. At the 6- to 8-week follow-up, there were six partial remissions, two mixed responses, and six patients with progressive disease. In the 12 patients followed >1 year, there have been no durable responses. Thus, although high-dose ¹⁵³Sm-EDTMP + gemcitabine has moderate palliative activity (improved pain; radiologic responses) in this poor-risk population, additional measures of local and systemic control are required for durable control of relapsed osteosarcoma with osteoblastic lesions. The strategy of radioactive drug binding to a target followed by a radiosensitizer may provide synergy and improved response rate.

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