The co-authors of Invasion of the Prostate Snatchers, blog alternate posts weekly. We invite you to post your comments.

Tuesday, June 18, 2013

Xofigo—A Wonderful New Treatment for Men with Advanced Prostate Cancer


It’s a special event when the FDA approves a new treatment.  Xofigo, otherwise known as Radium 223 or Alpharadin, is now commercially available.  The FDA approved Xofigo based on the results of a large, prospective, placebo-controlled trial that demonstrated significantly greater survival in Xofigo-treated men compared to placebo-treated men.  The trial also shows a very low incidence of side effects and good relief of bone pain. The treatment is easy to administer, consisting of monthly intravenous injections.

How Xofigo Works
Cancer treatment falls into four major categories. Chemotherapy selectively targets fast growing cells. Unfortunately, since chemotherapy works as a nonspecific cell poison, it frequently causes prominent side effects. Hormonal and targeted agents work by blocking the internal mechanisms of the cancer cell, thus forestalling growth. These treatments tend to have fewer side effects than chemotherapy.  However, by nature cancers are genetically variable, so resistant clones eventually appear. Immunotherapy stimulates the patient’s immune system. New forms of immunotherapy are promising and development is progressing very rapidly but this area of study is still in its infancy. Lastly, there is radiation consists of high energy particles that blast cellular DNA. A cancer cell with disabled DNA can’t reproduce.

Radiation needs to be given in a dosage sufficiently large enough to be effective. However, it also has to be targeted accurately to spare the surrounding healthy tissue. Xofigo addresses both of these demands elegantly. In terms of power, just one of the alpha particles emitted by radium 223 can cause irreversible cell damage because alpha particles are large enough to sever double-stranded DNA (typical beam radiation with photons requires multiple hits on DNA because it only damages one of the two DNA strands).

Xofigo Targets the Bone Metastasis
When cancer invades the calcium matrix of the bone it stimulates the bone to accelerate its rate of calcium uptake.  Radium 223 has structural similarities to calcium so Xofigo is “mistakenly” taken up by the bone cells adjacent to the cancer in lieu of calcium. So after Xofigo is injected, it travels through the blood stream and concentrates in the irritated areas of the bone where the cancer is most active.

Xofigo would be effective against almost any type of cancer since most cancers that spread to the bone increase calcium turnover in the bone cells adjacent to the cancer. However, the manufacturers and distributors, Algeta and Bayer Pharmaceuticals, were wise to seek FDA approval for prostate cancer before pursuing development in other types of cancer. Prostate cancer has an extremely fastidious pattern of spread. Metastases occur almost exclusively in bone. The major organs like lung, liver, kidney or brain are almost always spared. Since prostate cancer spreads almost exclusively to bone, Xofigo targets most if not all of the disease.

Alpha Particles Only Travel a Few Micrometers
To most everyone, the thought of radiation easily conjures up horrible visions of toxicity. The concept of radiation by injection is not new. Strontium and samarium are two radioactive elements that also concentrate in areas of increased bone activity. However, they emit a different type of radiation, beta radiation, which acts over a much longer distance and induces collateral damage to the surrounding cells in the bone marrow, the cells of the all-important immune system. Fortunately, bone marrow toxicity appears to be rare in men treated with Xofigo because alpha particles characteristically dissipate over the distance of a couple of micrometers, restricting the radiation effect to the active area of the cancer where it is invading on the surface of the bone.

Potent, Highly-Targeted Therapy—Just What the Doctor Ordered
Advanced prostate cancer in the bones eventually becomes resistant to other treatments. Historically, external beam radiation therapy has been a potent method for killing cancer cells, particularly to control pain, when the effectiveness of other options seems to be failing. However, beam radiation must be used very judiciously because it also causes irreversible damage to the surrounding bone marrow. Xofigo is likely to rapidly gain widespread acceptance with both doctors and patients because it simultaneously targets multiple metastases yet spares the closely adjacent bone marrow.

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