Abiraterone Acetate for Prostate Cancer
Most cases of prostate cancer are usually curable by surgery or radiation therapy. A small percentage of patients have recurrences after primary therapy, or are incurable from the beginning. In either of these situations tumor growth may vary from slow to intermediate to aggressive. Testosterone initially fuels this growth; therefore, standard treatment is to remove the main source of testosterone production by means of either medical or surgical treatment. This procedure very frequently halts the tumor’s progress, sometimes quite dramatically. Eventually, despite an initial favorable response and low levels of testosterone, cancer begins to grow again. This situation has been called “hormone-resistant prostate cancer”. One reason for relapse after castration is that too much residual testosterone remains in the body because the adrenal glands and the cancer itself may continue to produce hormones in small but significant amounts. In addition, the tumor also may develop increased numbers of hormone receptor proteins, which function to send more growth signals.
Hormone-resistant prostate cancer is an advanced stage of the disease with a three year survival potential of only 20%. Obviously, if there were some way to block residual hormone production it might be possible to create a total, or near total absence of testosterone. Although a drug that blocks hormone production has been available for years, it has many side effects and a low response rate. A new agent that blocks male hormone production, abiraterone acetate, was discovered at the Institute of Cancer Research in London, and the first reported Phase I study in 2007 seemed very promising. Further trials showed it to be more potent and less toxic than the previous alternative. Phase II trials showed a significant decline in the tumor marker PSA as well as tumor shrinkage in about half the treated patients. A large phase III trial of patients previously treated with chemotherapy proved that abiraterone acetate produced significantly longer responses and a 36% increase in median survival as compared to a placebo.
Tower Cancer Research Foundation has been an important research site for the abiraterone acetate trial for nearly three years. The trials at all sites have now been completed, and on April 28, 2011 the FDA approved abiraterone acetate under the trade name Zytiga®.
Prostate cancer is very common and has a high cure rate. However, approximately 30,000 deaths still occur annually in the US. When standard hormone deprivation therapy is no longer effective, the outlook for patients has been disappointing. The drug abiraterone acetate seems to be an important breakthrough in this setting. Clinical trials have showed improvement in the quality of life as well as the extent of life in patients with castrate resistant prostate cancer. Hopefully, as Zytiga® enters the marketplace, it will fill a much needed niche for patients with advanced prostate cancer.