Castration-resistant prostate cancer (CRPC) is also known as HRPC (hormone-refractory prostate cancer). Most patients with CRPC have bone metastases, according to radiological evidence. When the cancer establishes itself in the bone, it undermines bone strength - the patient may feel pain, is more vulnerable to fractures and other complications which can impair his health considerably. Prostate cancer that spreads to the bone usually targets the lumbar spine, pelvis and vertebrae. The main cause of disability and death among those with CRPC is bone metastases.
Bayer HealthCare, the maker of Alpharadin, explained that all the secondary endpoints were also met, which included delay in time to first SREs (skeletal-related events).
According to the researchers, those in the trial who received Alpharadin:
- Had a median overall survival of 14 months, versus 11.2 months for those on placebo (dummy drug)
- Had a median time to first SREs of 13.6 months compared to 8.4 months in the placebo group - an improvement of 64%
- 33% of Alpharadin patients had a total ALP (alkaline phosphatase) normalization, compared to just 1% in the placebo group
- Had an improvement of 49% in time to PSA progression
Adverse events - 15% experienced non-hematologic adverse events, including bone pain, nausea, diarrhea, constipation and vomiting. Anemia was the most common hematologic event, affecting 18% of patients. Bone pain, the most common Grade 3 to 4 adverse event was experienced by 18% of patients on Alpharadin.
Principal investigator of ALSYMPCA, Dr. Chris Parker, of the Royal Marsden Hospital, London, said:
"These data are significant because they demonstrate that Alpharadin can prolong life in patients with castration-resistant prostate cancer and bone metastases. These results and previous study findings suggest that Alpharadin, a novel alpha-pharmaceutical, may provide a new standard of care for the treatment of castration-resistant prostate cancer patients with bone metastases."
The FDA (Food and Drug Administration), USA, recently granted Alpharadin Fast Track designation.
Bayer HealthCare says it plans to submit Alpharadin for approval to regulatory authorities in Europe and the USA in the middle of next year - based on present data.
ALSYMPCA TrialThis was a Phase III, randomized, placebo-controlled, double-blind international human study comparing Alpharadin combined with best standard care against placebo combined with best standard care in men with symptomatic CRPC that has metastasized to the bone. It involved 922 patients in over 100 centers in 19 different nations. They were all either ineligible for docetaxel, could not tolerate it, or had not responded to therapy with docetaxel.
Patients were given either Alpharadin or a placebo intravenously up to six times, four weeks apart.
The study's primary endpoint was overall survival, secondary endpoints were time to SRE occurrence, alterations and time to progression in PSA and ALP, safety, and the medication's impact on quality of life.
The trial was initiated by Algeta ASA, Oslo, Norway, in 2008.
AlpharadinAlpharadin (radium-223 chloride) is a pharmaceutical which contains an alpha-particle emitting nuclide - an investigational alpha-pharmaceutical. It is being developed for use on patients with bone metastases. The compound mimics several of calcium's behaviors in the bone.
Alpharadin uses alpha radiation (from radium-233 decay) to destroy cancer cells. Radium-223 naturally targets bone metastases due to its calcium-mimicking properties. Alpha radiation has a much shorter range than current beta/gamma radiation - it causes less damage to surrounding tissue, especially bone marrow. Any Alpharadin that is not taken up by bone metastases is immediately excreted through the gut.
Written by Christian Nordqvist