Data from Alpha Particle Radium 223 Dichloride in High-risk Osteosarcoma: A Phase I Dose Escalation Trial Article Swipe
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· 2023
· Open Access
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· DOI: https://doi.org/10.1158/1078-0432.c.6528264
· OA: W4361959806
<div>AbstractPurpose:<p>The prognosis of metastatic osteosarcoma continues to be poor. We hypothesized that alpha-emitting, bone-targeting radium 223 dichloride (<sup>223</sup>RaCl<sub>2</sub>) can be safely administered to patients with osteosarcoma and that early signals of response or resistance can be assessed by quantitative and qualitative correlative imaging studies and biomarkers.</p>Patients and Methods:<p>A 3+3 phase I, dose-escalation trial of <sup>223</sup>RaCl<sub>2</sub> (50, 75, and 100 kBq/kg) was designed in patients with recurrent/metastatic osteosarcoma aged ≥15 years. Objective measurements included changes in standardized uptake values of positron emission tomography (PET; 18FDG and/or NaF-18) and single-photon emission CT/CT (99mTc-MDP) as well as alkaline phosphatase and bone turnover markers at baseline, midstudy, and the end of the study.</p>Results:<p>Among 18 patients enrolled (including 15 males) aged 15–71 years, tumor locations included spine (<i>n</i> = 12, 67%), pelvis (<i>n</i> = 10, 56%), ribs (<i>n</i> = 9, 50%), extremity (<i>n</i> = 7, 39%), and skull (<i>n</i> = 2, 11%). Patients received 1–6 cycles of <sup>223</sup>RaCl<sub>2</sub>; cumulative doses were 6.84-57.81 MBq. NaF PET revealed more sites of metastases than did FDG PET. One patient showed a metabolic response on FDG PET and NaF PET. Four patients had mixed responses, and one patient had a response in a brain metastasis. Bronchopulmonary hemorrhage from Grade 3 thrombocytopenia (<i>N</i> = 1) was a DLT. The median overall survival time was 25 weeks.</p>Conclusions:<p>The first evaluation of the safety and efficacy of an alpha particle in high-risk osteosarcoma shows that the recommended phase II dose for <sup>223</sup>RaCl<sub>2</sub> in osteosarcoma is 100 kBq/kg monthly (twice the dose approved for prostate cancer), with minimal hematologic toxicity, setting the stage for combination therapies.</p></div>
