Radium-233 Shows Efficacy in Hormone Refractory Prostate Cancer

Marlene Busko

June 14, 2007

June 14, 2007 — Radioisotope radium-223 has shown promise as a new treatment for patients with bone metastases resulting from hormone-refractory prostate cancer (HRPC). The results of a small study suggest a potential beneficial effect of radium-223 on the risk for skeletal-related events (SREs), progression of prostate-specific antigen (PSA), and overall survival. The findings were presented at the American Society of Clinical Oncology 43rd Annual Meeting in Chicago and simultaneously published online June 3 in Lancet Oncology.

Patients with HRPC frequently develop bone-marrow involvement at an early stage, which generally leads to metastases within the skeletal system. Affected individuals will often experience symptoms such as bone pain, spinal-cord compression, pathological fracture, and pancytopenia. In their paper, the researchers point out that existing bone-targeted treatments, such as beta-emitting radioisotopes and bisphosphonates, have limitations. Zoledronate, for example, is able to reduce the risk for SREs but has shown no impact on survival. The beta-emitting radioisotope strontium-89 can reduce pain in patients with symptomatic HRPC, but toxicity may limit the dosage.

Christopher Parker, MD, a senior lecturer and honorary consultant in clinical oncology at the Institute of Cancer Research and Royal Marsden Hospital, in Sutton, United Kingdom, and colleagues evaluated the use of radium-223 in a phase 2 trial involving 64 patients with HRPC and painful bone metastases. The researchers selected radium-223 because it emits alpha radiation, which has a higher energy and lower range than beta emitters. This may give it a greater antitumor effect because of the densely ionizing abilities of its high linear-energy transfer radiation, and it may also be more sparing of bone marrow because of its short-track length, they explain.

The team points out that in an earlier phase 1 study in patients with HRPC and metastatic bone disease, radium-233 appeared to be reasonably well tolerated, without any reported grade 2+ thrombocytopenia or dose-limiting toxic effects. There was also preliminary evidence of efficacy, as observed by substantial decreases in serum alkaline phosphatase (ALP) concentrations, which is considered a marker for progression of HRPC, and improvements in pain control across all levels of dosing.

In the current study, patients were randomized to receive 4 intravenous doses of radium-233 (50 kBq/kg, n = 33) or placebo at 4-week intervals. All patients also received external-beam radiotherapy and were followed for at least 18 months.

The level of ALP decreased by 65.6% in the group receiving radium-223 but increased 9.3% in the placebo group. There was also a significant improvement in men receiving radium-233 in both median survival (65.3 weeks, vs 46.4 weeks in the control group) and time to PSA progression (26 weeks, vs 8 weeks in the control group).

The researchers also did not observe substantial differences in hematological adverse events between the 2 groups. Grade 2+ thrombocytopenia was reported in 1 patient in the placebo group, but in not in any patients who received radium-233. Three patients in the radium-233 group experienced grade 2+ neutropenia, but it was reversible and most commonly seen during the first 4 weeks of treatment. No evidence was observed of any cumulative myelotoxic effects.

"The results are very encouraging but are not sufficient to change clinical practice," Dr. Parker told Medscape. "It is striking that there was evidence of clinical benefit in the absence of any significant toxicity, and in particular no myelotoxicity."

"I believe that the data provide a strong case for phase 3 trials to study the effect of radium-223 on progression-free and overall survival in men with HRPC," he added.

Approached for a comment on the new findings, Paul Matthew, MD, assistant professor at the department of genitourinary medical oncology, University of Texas MD Anderson Cancer Center, in Houston, said he agreed. "It is too early to change current standards of care, and further studies are needed," he told Medscape. Radium-233 is "an interesting agent with a distinctive radiobiology and profile of action . . . [and] with multiple administrations may derive particular advantages over historical radioisotopes, either alone or in combination with cytotoxic therapy," he commented.

The study was sponsored by Algeta ASA in collaboration with TFS Trial Form Support, Hirrson Clinical Research, and Statisticon AB. Dr. Parker reported that he was an external consultant for Algeta and received payment from the company for writing the manuscript.

American Society of Clinical Oncology 43rd Annual Meeting: Abstract 5073. Presented June 2, 2007.

Lancet Oncol . 2007. Published online June 3, 2007.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.