Complete response of bone-only metastatic breast cancer to skeletal: Targeted radiotherapy with 166HOLMIUM-DOTMP

Abstract

569 Background: The skeleton is the most common and sometimes the only site of metastatic disease in breast cancer. We tested the feasibility of using 166Ho-DOTMP, which localizes to bone surfaces to deliver targeted high-dose radiation to bone metastases and the adjacent marrow. Patients received autologous stem cell infusions to restore hematopoiesis. Methods: Six women < 65 years old with breast cancer and bone-only disease participated in the study. They had received a median of 2.5 prior chemotherapy or hormonal treatment regimens. Five patients had stable disease and one patient had progressive disease before the high-dose radiation. A 30-mCi test dose of 166Ho-DOTMP was given to assess skeletal uptake; if uptake was adequate, a therapeutic dose estimated to deliver 22 Gy (n=3) or 28 Gy (n=3) was prescribed. Treatment was followed by autologous stem cell transplantation when the ongoing radiation dose to the marrow was < 1 cGy/hour. Results: 870–2065 mCi 166Ho-DOTMP dose was administered.? All subjects showed prompt trilineage hematologic recovery. The most common toxicity was mild nausea. None of the patients experienced grade 3–4 acute toxicity other than the expected myelosuppression. Two patients developed hemorrhagic cystitis 2 years after therapy, which resolved in both patients. One of these patients also had gastrointestinal bleeding and pseudomembranous colitis. One subject develops myelodysplastic syndrome but had trisomy 8 before treatment. Two patients remain progression-free without evidence of disease (complete response) for more than 5 years after study entry; 4 experienced disease relapse (all at extraosseous sites), and died of progressive disease. Median time to progression was 10 months. Conclusions: 166Ho-DOTMP had an acceptable toxicity profile, and two of the six heavily pretreated patients achieved sustained complete response. A phase II study is planned to evaluate the efficacy of this strategy for treatment of bone metastases. No significant financial relationships to disclose.