XOFIGO FOR OSTEOSARCOMA TREATMENT

NEW YORK (Reuters Health) - Radium 223 decreases the size of primary osteosarcoma lesions and metastases, including those in the brain, according to preliminary results from a first-in-humans clinical trial.

"Because osteosarcoma makes bone and radium-223 acts like calcium, this radiopharmaceutical could possibly become a new targeted means to achieve safe and effective reduction of tumor burden, as well as facilitate better surgery and/or radiotherapy for difficult-to-resect large, or metastatic tumors," Dr. Vivek Subbiah, from the University of Texas MD Anderson Cancer Center, Houston, told Reuters Health by email.

Radium 223, an alpha-emitting radiopharmaceutical with Food and Drug Administration approval for prostate cancer with bone metastases, is the subject of a phase 1 clinical trial for patients with progressive, locally recurrent, or metastatic osteosarcoma, designed by Dr. Subbiah and colleagues.

They describe the response of one patient, a man in his 20s with lung and brain metastatic osteosarcoma originating in the left femur, in their February 19 JAMA Oncology online report.

After three infusions of radium 223 dichloride at four-week intervals, researchers observed a reduction in positron-emission tomography-computed tomography (PET-CT) metabolic activity at most sites, including the dominant left cerebellar metastasis.

Magnetic resonance imaging (MRI) showed a decrease in the cerebellar lesion from 1.5 cm at baseline to 1.2 cm after treatment, with resolution of the perilesional edema.

Later imaging showed development of new cerebellar metastases smaller than 5 mm, at which time the patient was disenrolled from the clinical trial because of progressive disease.

Up to that point, the patient had reported a clinical reduction in bone pain and had experienced no grade 3 or 4 toxic effects related to radium 223.

"There was no prior evidence of blood brain barrier penetration of any alpha particle or radium 223," Dr. Subbiah said. "So we were pleasantly surprised."

"Because radium 223 has less marrow toxicity and more radiobiological effectiveness, especially if inside the bone-forming cancer cell, than samarium 153-EDTMP, radium 223 may have greater potential to become widely used against osteosarcoma as a targeted therapy," Dr. Subbiah concluded. "Radium 223 also has more potential to be used with chemotherapy against osteosarcoma and bone metastases."

"Radium should be further studied in osteosarcoma," Dr. Damon R. Reed, from H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, who recently reviewed osteosarcoma in pediatric patients and young adults, told Reuters Health by email.

This research was supported the Shannon Wilkes Foundation; the University of Texas MD Anderson Cancer Center; and grant CA016672 from the National Institutes of Health. Bayer AG donated the radioactive isotopes. The authors report no disclosures.

SOURCE: http://bit.ly/1A3tX0l

JAMA Oncol 2015.