Gemcitabine radiosensitization after 153Sm-EDTMP (quadramet) bone-seeking radioisotope therapy for osteoblastic lesions of osteosarcoma: Activity and principles

Abstract

8534 Background: Osteoblastic metastases 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. Methods: Fourteen patients with osteoblastic lesions of osteosarcoma were treated. With high-dose 153Sm-EDTMP (30 mCi/kg) and stem cell support. Gemcitabine was administered 1 day after samarium. Imaging studies used to assess response. Results: The 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). Expected cytopenias from skeletal binding of the radiopharmaceutical occurred within 14 days. Peripheral blood progenitor cells (PBPC) were infused 2 weeks after samarium in 11 patients; three patients had marrow infused. Blood count recovery was uneventful after PBPC in 11/11 patients. Toxicity from the daily gemcitabine regimen (250 mg/M2/day x 5) was excessive (grade 3 mucositis; N=1). Toxicity from a single infusion of gemcitabine (1500 mg/M2) in combination with 153Sm-EDTMP was minimal (pancytopenia). There were no reported episodes of hemorrhagic cystitis (hematuria) or nephrotoxicity. At the 6–8 week follow-up there were 6 PR, 2 mixed responses, and 6 patients with progressive disease. In the 12 patients followed >1 year, there have been no durable responses. Conclusions: High-dose 153Sm-EDTMP + gemcitabine has activity in osteoblastic osteosarcoma lesions, but recurrence is very common. Other strategies such as repeated standard doses of samarium with gemcitabine and/or use of additional measures of local and systemic control should be considered for more prolonged control of osteoblastic metastases. No significant financial relationships to disclose.