Format

Send to

Choose Destination
Clin Cancer Res. 2019 Jul 1;25(13):3802-3810. doi: 10.1158/1078-0432.CCR-18-3964. Epub 2019 Feb 7.

Alpha Particle Radium 223 Dichloride in High-risk Osteosarcoma: A Phase I Dose Escalation Trial.

Author information

1
Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas. vsubbiah@mdanderson.org.
2
Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
3
Department of Pediatric Hematology/Oncology, Cleveland Clinic Foundation Cleveland, Ohio.
4
Department of Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
5
Docrates Cancer Center, Helsinki, Finland.
6
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
7
Children's Center for Cancer and Blood Diseases, Children's Hospital of Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, California.
8
Department of Sarcoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
9
Sarcoma Oncology Center, Santa Monica, California.
10
Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
11
Department of Radiology, Baylor College of Medicine, Houston, Texas.

Abstract

PURPOSE:

The prognosis of metastatic osteosarcoma continues to be poor. We hypothesized that alpha-emitting, bone-targeting 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.

PMID:
30733229
PMCID:
PMC6606382
[Available on 2020-07-01]
DOI:
10.1158/1078-0432.CCR-18-3964

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center