CHICAGO – Investigators are reporting favorable results in a phase I pharmacokinetic and biodistribution study in men with bone metastases resulting from castration-resistant prostate cancer (CRPC) who received escalating doses of radium-223.
The findings were released at the 46th Annual Meeting of the American Society of Clinical Oncology (ASCO).
Jorge A. Carrasquillo, MD, with Memorial Sloan-Kettering Cancer Center in New York City, and colleagues assessed the dose-limiting toxicity (DLT) of radium-223 in ten patients during the first four weeks after treatment.
Radium-223, a calcium mimetic, alpha-emitting nuclide, is a first-in-class alpha-pharmaceutical with a potent and highly targeted antitumor effect on bone metastases and a highly tolerable side effect profile.
Study participants, all of whom had progressive CRPC and at least two bone metastases, were treated in cohorts of three to six patients with a single dose of 50, 100, 200 kBq/kg followed by one optional dose of 50 kBq/kg six weeks later.
Results showed that radium-223 was well tolerated.
No maximum tolerated dose for radium-223 was reached in the study, up to 200 kBq/kg.
Also, radium-233 cleared the blood and accumulated in bone metastases as early as 10 minutes from the time of injection.
Based on the results of the phase I pharmacokinetic and biodistribution study, a phase I/IIa trial in combination with docetaxel is planned and a phase III survival study is currently underway. The phase III Alpharadin in Symptomatic Prostate Cancer (ALSYMPCA) study is comparing overall survival in men with symptomatic CRPC with bone metastases who have been randomized to the best standard of care plus either radium-223 or placebo.
Roughly 90 percent of men with CRPC, formerly known as hormone-refractory prostate cancer (HRPC), have radiological evidence of bone metastases. Bone metastases may cause bone pain, fracture and other complications that can significantly impair health. In fact, bone metastases are the main cause of disability and death in men with CRPC.
Written by Jill Stein