Increasing doses of radium chloride effective, tolerated in prostate cancer

By Sally Robertson, B.Sc.Sep 26 2012

Radium chloride (Ra 223) treatment has dose-dependent beneficial effects on health outcomes in patients with castration-resistant prostate cancer (CRPC) and bone metastases, report researchers.

"This study supports the safety and tolerability of Ra 223 to the highest dose level (80 kBq/kg)," say Christopher Parker (Royal Marsden Hospital, London, UK) and team.

"The AE [adverse event] profile was consistent with expectations for advanced prostate cancer, with no clear dose-toxicity relationship in treatment-related AEs or in the pattern of hematologic events."

As reported in European Urology, the team administered three Ra 223 injections at 25, 50, and 80 Bq/kg doses to 41, 39, and 42 patients, respectively, at 6-week intervals. The patients then underwent follow-up assessment at 24 weeks and 12 and 24 months.

The study was intended to inform the dose choice for future trials following significantly improved overall survival after Ra 223 administration in a previous placebo-controlled trial.

By the end of the 24-week treatment period, prostate-specific antigen (PSA) levels were reduced by at least 50% in no patients, two (6%) patients, and five (13%) patients in the 25, 50, and 80 Bq/kg dose groups, respectively. Levels of bone alkaline phosphatase (ALP) also decreased by at least 50% from baseline in six (16%), 24 (67%), and 25 (66%) patients in the respective dose groups.

A total of 112 patients reported one or more adverse events, the most common being diarrhea (21%), nausea (16%), and anemia (14%) which occurred up to week 24 across all dose groups. Overall, there was no apparent dose response effect on adverse events, apart from a slight trend toward an increase in gastrointestinal adverse events.

Median values for white blood cell count, neutrophils, platelets, and hemoglobin decreased following Ra 223 administration, with no significant differences observed between the dose groups. However, with the exception of hemoglobin, these measures returned to baseline levels at the end of the 24-week treatment. There were no significant differences between the dose groups in these hematologic parameters.

Survival analysis showed that 24 months after the first injections, 26, 22, and 22 people died in the 25, 50, and 80 kBq/kg dose groups, respectively, and the median times to death were 548, 569, and 604 days, with no significant between-group differences observed.

"Ra 223 was well tolerated at all dose levels and had a dose dependent effect on serum levels of PSA and bone ALP," say Parker et al.

Ra 233 is a calcium mimetic that naturally self-targets to bone metastases and generates highly localized radiation zones to induce nonrepairable, double-stranded DNA breaks in metastatic cells.

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