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October 2008 Volume 2 #3
 HIFU or HYPE-U? New therapy for advanced PCa to be tested Male depression and prostate cancer The WWPCC in Geneva |
New therapy for advanced prostate cancer to be tested in Australia  A new and promising approach to treating advanced prostate cancer will soon be tested on patients in Australia, reported Dr. Wayne Tilley at this year's 4th Pacrim Breast and Prostate Cancer Meeting in Whistler, BC, where he was awarded the meeting's highest honour.Tilley and colleague Dr. Lisa Butler, researchers at the University of Adelaide, believe that, by combining low doses of bicalutamide (Casodex®) with either 17-AAG or vorinostat, they can expect to treat advanced prostate cancer more effectively and with fewer side effects. Bicalutamide is an anti-androgen currently used in hormone therapy. It works by preventing testosterone from attaching (binding) to the receptors on the surface of the prostate cancer cells. Without testosterone, the cancer cells either grow more slowly or not at all. Unfortunately, Tilley explains, in spite of an initial response to anti-androgens, cancer cells often develop a resistance to hormone deprivation, and the tumour starts to grow again. The drug 17-AAG (17-N-allylamino-17-demethoxygeldanamycin) is an anti-tumour antibiotic that has been undergoing phase I/II clinical trails, at least in the United States, since 1999. It works by inhibiting the work of Hsp90, a heat shock protein that acts as a kind of molecular chaperone of other proteins and so plays a supporting role in androgen reception and in the promotion and growth of tumour cells. Recent clinical trials suggest that Hsp90 inhibitors such as 17-AAG re-sensitize cancer cells to drugs to which they have become resistant. Vorinostat (suberoylanilide hydroxamic acid) is a drug that inhibits histone deacetylase, an enzyme that plays a key role in the regulation of cell survival, cell growth, and eventual cell death. Consequently, the drug has the potential to affect a tumour's ability to survive. Vorinostat in combination with the chemotherapy drug docetaxel is currently in phase I testing as a treatment for advanced and relapsed prostate cancer. (For information on this clinical trial, click here.) According to Tilley, bicalutamide and other hormone therapies are currently given at doses that can cause men to experience side effects, such as "reduced libido, impotence, hot flushes, tiredness and sweating, gradual decreases in body hair, reduced bone and muscle strength, and cognitive changes." And 17-AAG and vorinostat, although they block key cancer survival pathways, are "not particularly effective in killing prostate cancer cells if given alone." Combine these difficulties with the more serious possibility that a man's prostate cancer may no longer respond to conventional hormone therapy, and you get an urgent medical research question: Will some combination of drugs work better to combat advanced prostate cancer? Tilley and Butler think so. They have successfully killed prostate cancer cells in laboratory studies using low doses of bicalutamide and either of the other two drugs. "We can now confirm that a very low level of bicalutamide is capable of inhibiting cancer cell proliferation by more than 10-fold when combined with either vorinostat or 17-AAG, making our current treatments much more effective and causing fewer side effects," reports Butler. But, of course, the most important tests are yet to come. Dr. Christopher Sweeney, a medical oncologist at the Royal Adelaide Hospital Cancer Centre and its Director of Clinical Trials, will lead a team to examine the efficacy of this combination of drugs outside the lab. "The ultimate test of this exciting laboratory breakthrough is to see if it improves outcomes and quality of life for men suffering from advanced prostate cancer," he emphasizes. |
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