Discussant Dr. Wim J.G. Oyen of the St. Radboud University Medical Center Nijmegen, the Netherlands, said that based on phase I/II data suggesting that combining beta radiation–emitting agents with chemotherapy prolongs overall survival, the next logical step would be to add radium-223 in regimens of combination therapy.
"It’s so extremely well tolerated, I do not think we will experience synergistic toxicity, but we may very well experience synergistic effect," he said.
Dr. Oyen said that clinicians could further improve patient outcome by using radium-223 in the adjuvant setting (for example, in patients at high risk of developing clinically overt bone metastases). He said it is widely known that the smaller the tumor, the more advantage an alpha particle has over a beta particle; thus, microscopic disease would theoretically be the better indication over macroscopic disease.
Dr. Parker said in an interview that his preference would be to combine radium-223 with abiraterone acetate (Zytiga) because both improve survival and are extremely well tolerated, but they work in completely different ways.
Two small phase I/II trials are currently underway. One combines radium-223 with docetaxel in patients with CRPC and bone metastases. The second is studying radium-223 in breast cancer patients who have bone-dominant disease and are no longer eligible for endocrine therapy.
Dr. Parker reported serving as an uncompensated consultant to Algeta ASA and Bayer Healthcare Pharmaceuticals, which sponsored the trial. A coauthor reported an ownership interest in and previous employment with Algeta. A second coauthor is a Bayer employee.