CHICAGO—Alpharadin, an investigational agent, may relieve pain and improve survival in men with metastatic castration-resistant prostate cancer (CRPC), according to data presented at the American Society of Clinical Oncology annual meeting.

“This is a bone-seeking agent that is a first-in-class [medication],” said principal investigator Sten Nilsson, MD, Professor of Oncology at Karolinska University in Stockholm, Sweden. “It delivers a very, very strong cell killing activity. It also kills all cells irrespective of cell cycle phase and receptor expression.  So, I think this is the dramatic advantage with this new pharmaceutical.”

Alpharadin is a calcium mimetic, alpha-emitting nuclide, which has a potent and highly targeted anti-tumor effect on bone metastases.

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Dr. Nilsson and his colleagues analyzed data from two open-label phase 1 trials (total of 37 patients) and three double-blind, placebo-controlled phase 2 trials (total of 255 patients). All men had CRPC with bone metastases. In these trials, patients experienced significant improvement in bone markers and decreases in PSA levels and pain. In one of the placebo-controlled trials, median overall survival was greater in the alpharadin groups compared with placebo recipients (65 vs. 46 weeks).

The uptake of alpharadin into bone metastases occurs rapidly. In a separate analysis of data from a phase 1 pharmacokinetic and biodistribution study, the researchers found that alpharadin accumulates in bone metastases as early as 10 minutes from the time of injection.

In addition, the drug exhibits minimal activity in the kidneys, liver, or other internal organs. Of the 292 patients in the phase 1 and 2 trials, fewer than 1% experienced CTC grade 4 hematological toxicity, about 4% experienced grade 3 anemia, and fewer than 3% of the patients experienced grade 3 platelets, neutrophils or white blood cells.   The most common adverse events seen in all studies were nausea (33% of patients), bone pain (30%), fatigue (26%), diarrhea (26%), vomiting (20%), and constipation (20%). The researchers observed no signs of renal or hepatic toxicity.

“This pharmaceutical has proven to be very, very safe,” Dr. Nilsson said. “It has a benign side effect profile. It gives very little toxicity to the bone marrow, which is the main risk organ in this disease. It is excreted in the bile and intestines so we don’t see any toxic effects on the kidneys.”

Researchers are evaluating alpharadin in a global phase 3, randomized, double-blind, multi-dose, placebo-controlled international clinical trial in men with CRPC with bone metastases.