Xtandi (Formerly MDV3100) Approved by the FDA for Treatment of Hormone- and Chemotherapy-Resistant Prostate Cancers.

On August 31st, 2012, the Food and Drug Administration (FDA) approved MDV3100 (now known as Xtandi) for treatment of prostate cancers in men who have previously failed hormone and chemo therapies. (See the full story in the August 31st issue of the Prostate Cancer Foundation, PCF, NewsPulse). In its Phase III clinical trials, Xtandi increased median survival by 4.8 months (18.4 versus 13.6 months) over patients receiving the placebo. Overall, some patients had lengthy remissions well beyond the average time while others did not respond. These positive results led to the Phase III clinical trial being stopped early and the drug then being offered to patients in the placebo arm of the study due to its effectiveness in causing remissions and its high patient tolerability.  [This was also the case during the Phase III clinical trials for Zytiga (abiraterone acetate) in 2011.]  Xtandi has a novel mechanism of action. It does not shut off the production of testosterone but instead blocks testosterone’s effects by directly blocking the activity of the androgen (hormone) receptor at three distinct points, thus interfering with the “engine” of prostate cancer progression.  By comparison, Zytiga affects cancer progression by shutting off the cell’s supply of testosterone, the “fuel” that drives the “engine”. Both Zytiga and Xtandi are administered orally and are currently being evaluated in Phase III trials in patients who have failed hormone therapy but have not yet received chemotherapy. Further efforts will concentrate on testing both drugs in men with early recurrence of prostate cancer.  In addition, both drugs are also being tested in a pre-surgical condition, prior to prostatectomy, with the intent of potentially curing primary, high-risk prostate cancer.  Having both drugs available represents an important advance in patient treatment. The nine-year research and development period for Xtandi has been relatively short when compared  to twelve years or more for other drugs. Xtandi will be distributed jointly by its co-developers, San Francisco’s Medivation, Inc. and the Japanese company, Astellas Pharma, Inc.


An Example of Potential New Prostate Cancer (PC) Treatments on the Horizon. Killing PC Cells With Radioactive Gold Nanoparticles Containing a Component of Tea as the Targeting Agent.

Boca Pass (Connecting Charlotte Harbor and the Gulf of Mexico), Boca Grande, Florida

Nanotechnology is finding potential applications in many areas of our lives including cancer.  [A nanometer is defined as one billionth of a meter or one ten millionth of a centimeter (there are 2.54 centimeters per inch).] Synthetic nanometer-sized particles (such as atoms, molecules or fragments thereof usually less than 100 nanometers in size) are being used in many areas of current research including the medical sciences, electronics, optics, magnetics, information technology and materials development. An article recently appeared in the July 16th, 2012 Proceedings of the National Academy of Sciences (PNAS) which described the injection into mouse prostate tumors of nanoparticles consisting of an isotope of radioactive gold (Au -198, used to destroy the tumor) coupled with a compound found in tea (epigallocatechin gallate, EGCg), used to specifically target the nanoparticle to prostate cancer cells. This type of therapy could minimize many of the potential side effects from current modes of chemotherapy. The radioactive gold-198 isotope releases beta-particles (streams of electrons) which are stopped very easily by an adjoining barrier thereby killing nearby tumor cells without penetrating surrounding normal tissues.  The radioactive gold-198 loses its radioactivity within three weeks. The particles were just the right size such that they remained within the tumor once it was reached with the help of the EGCg compound from tea which has an affinity for prostate cancer cells (specifically laminin67R receptors which are over-expressed in prostate cancer cells).  Tumor volume was reduced in mice by approximately 80% and nearly 75% of the nanoparticles remained trapped in the prostate gland after injection. A description of the research also appeared in the August 14th, 2012 Nanotech News.  Since these initial results were in mice, further preclinical work is needed before any potential application in humans. However, it demonstrates a new method of chemotherapy for prostate and other solid tumors using specifically-targeted nanoparticles.  The work was supported in part by the National Cancer Institute (of the National Institutes of Health , NIH) Alliance for Nanotechnology in Cancer.