Osteoblastic
metastases and
osteosarcoma can avidly concentrate bone-seeking
radiopharmaceuticals. We sought to increase effectiveness of high-dose (153)
Samarium 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.