CHICAGO - The investigational alpha-pharmaceutical radium-223 chloride (Alpharadin) appears to confer multiple benefits in men with metastatic castration-resistant prostate cancer (CRPC), researchers announced at the 46th Annual Meeting of the American Society of Clinical Oncology (ASCO).

Results in two open-label phase 1 trials and three double-blind phase II trials showed that the agent improved survival, reduced pain, and had a tolerable safety profile when used to treat men with CRPC with bone metastases. Bone metastases are the main cause of disability and death in men with CRPC.

Dr. Sten Nilsson, with Karolinska University Hospital in Stockholm, Sweden, was the lead investigator in the study.

Radium-223, a calcium mimetic, alpha-emitting nuclide, is a first-in-class alpha-pharmaceutical which has a potent and highly targeted antitumor effect on bone metastases and a highly tolerable side effect profile.

In the studies, which included a total of 292 patients, radium-223 doses varied from 5 to 250 kBq/kg b.w. and were given as either single or repeat injections.

The investigators conducted assessments of safety, efficacy, and dosimetry.

Results showed that radium-223 was rapidly eliminated from blood with uptake into bone metastases and excretion into the small intestine with no hepatobiliary excretion, and minimal activity in the kidneys, liver, or other internal organs.

Fewer than 1% of patients in the combined analysis experienced common toxicity criteria (CTC) grade 4 hematological toxicity, about 4% experienced grade 3 anemia, and fewer than 3% had grade 3 platelets, neutrophils or white blood cell count (WBC).

Side effects observed in 20 to 33% of patients in all studies included nausea, bone pain, fatigue, diarrhea, vomiting, and constipation.

There was no evidence of renal or liver toxicity.

The investigators also documented a significant decrease on bone markers and prostate-specific antigen (PSA) and an improvement in pain.

The median overall survival improved in the radium-223 group compared to the placebo group (65 versus 46 weeks, p=0.017).

Radium-223 is currently being tested in the global, phase 3 ALSYMPCA (Alpharadin in Symptomatic Prostate Cancer) trial in men with symptomatic CRPC and bone metastases. The study is comparing the efficacy of best standard of care plus radium-223 versus best standard of care plus placebo, with overall survival as the primary efficacy endpoint. The trial has a target recruitment of 900 patients.

Prostate cancer is the most common cancer in men in the U.S. and in northern European countries. In 2002, roughly 680,000 men had prostate cancer and 220,000 died from the disease worldwide.

Alpharadin is being developed under a license and development agreement between Bayer-Schering Pharma in Berlin, Germany, and Algeta ASA, in Oslo, Norway.

Jill Stein
Jill Stein is a Paris-based freelance medical writer.