Alpha particle radium 223 dichloride in high-risk osteosarcoma: A phase i dose escalation trial

Vivek Subbiah, Pete M. Anderson, Kalevi Kairemo, Kenneth Hess, Winston W. Huh, Vinod Ravi, Najat C. Daw, Neeta Somaiah, Joseph A. Ludwig, Robert S. Benjamin, Sant Chawla, David S. Hong, Funda Meric-Bernstam, Gregory Ravizzini, Eugenie Kleinerman, Homer Macapinlac, Eric Rohren

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Purpose: The prognosis of metastatic osteosarcoma continues to be poor. We hypothesized that alpha-emitting, bonetargeting radium 223 dichloride (223RaCl2) 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. Patients and Methods: A 3+3 phase I, dose-escalation trial of 223RaCl2 (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. Results: Among 18 patients enrolled (including 15 males) aged 15-71 years, tumor locations included spine (n = 12, 67%), pelvis (n = 10, 56%), ribs (n = 9, 50%), extremity (n = 7, 39%), and skull (n = 2, 11%). Patients received 1-6 cycles of 223RaCl2; 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 (N = 1) was a DLT. The median overall survival time was 25 weeks. Conclusions: The first evaluation of the safety and efficacy of an alpha particle in high-risk osteosarcoma shows that the recommended phase II dose for 223RaCl2 in osteosarcoma is 100 kBq/kg monthly (twice the dose approved for prostate cancer), with minimal hematologic toxicity, setting the stage for combination therapies.

Original languageEnglish (US)
Pages (from-to)3802-3810
Number of pages9
JournalClinical Cancer Research
Volume25
Issue number13
DOIs
StatePublished - 2019

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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