Proscar for the Treatment of Prostate Cancer?

Proscar is an FDA approved medication used for the treatment of benign swelling of the prostate. It is a well-tolerated, nontoxic medication. It works by blocking the enzyme 5 alpha reductase that converts testosterone into its most potent form, dihydrotestosterone(DHT). In the adult DHT is the major growth hormone of the prostate cell. Since this more potent form of testosterone is blocked by Proscar from being created, the normal prostate gland experiences a relative deprivation of testosterone. The prostate gland needs the ongoing presence of DHT and testosterone to exist and function. When the gland experiences a decline in DHT it begins to shrink.

Prostate cancer, which is derived from the same cells that make up the prostate gland also needs testosterone and DHT to grow and flourish. Testosterone and DHT receptors are found on prostate cancer cells. A number of medications used to treat prostate cancer including Lupron, Zoladex, Flutamide, Casodex, Nilutamide, Cyproterone, and others all express their anti-cancer activity via some manner of testosterone-blocking. Since Proscar is an agent that can limit the formation of testosterone in its most potent form, dihydrotestosterone, it is a likely candidate for anti-cancer activity.

Most studies of Proscar in prostate cancer have occurred in very advanced disease at a time when multiple other cancer agents have failed. Results of those studies have demonstrated minimal benefit from Proscar. More recently an abstract has been published about a study using Proscar as the first and only treatment in men who develop rising PSA levels after having undergone radical prostatectomy. Such a situation is essentially equivalent to relapsing cancer. These were people who had had their prostates out and who had PSA levels between 1 and 10, people with relatively low volume disease. The study evaluated two groups one of which received Proscar and the other which received placebo. Comparisons in the PSA levels between the two groups were made after 12 and 24 months. PSA levels in the Proscar treated group dropped and took an average of one year to climb back up to the original starting level of that particular patient. The placebo group had a steady rise in PSA levels. Interestingly the patients who started treatment with Proscar when their PSA level was less than one took 24 months before their PSA levels returned to their starting levels.

We believe that one can conclude from this study that Proscar definitely has anticancer activity though it may be modest. This modest activity however may not be inconsequential. It has already been demonstrated in the studies with Lupron and Flutamide that more complete testosterone deprivation can translate into a longer life even in men with very advanced disease. Presently more and more men are now being treated with testosterone blocking agents at the earlier stages of disease(low PSA levels). These early stages are substantially more susceptible to hormone blocking than are the advanced stages. It is possible that even the modest effects of Proscar when used on top of the traditional agents such as Lupron and Flutamide might translate into significantly increased cell kill.

Mainline oncologic principles support this sort of argument. A variety of different cancers have been studied in which relatively weak anti-cancer agents were evaluated in the advanced stages of breast and colon cancer and found to be of limited benefit. When these same agents were utilized at the earliest stages, ie high risk patients after surgery, studies have proven that a portion of these patients are cured!

Success in these studies of breast and colon cancer has usually been based on the principal of using maximal therapy at the earliest stage of disease. The same line of thought has led us to considering that the additional blocking effect of Proscar may ultimately prove to be of real clinical benefit when it is added to the already established treatment of Lupron and Flutamide. Unfortunately there is absolutely no scientific support for this premise. Nor will there be any in the near future; We am not aware of any studies presently ongoing to try to answer this question. In the absence of any conclusive studies we feel it is our job to make our patients aware of the possible but unproven benefit of Proscar in this situation. It is our judgement that it is highly unlikely that Proscar will cause harm or significant side effects based on its extensive evaluation in the treatment of benign swelling of the prostate. Unfortunately in the absence of any good science, the responsibility for choices in the use of Proscar will have to rest with our patients.

 
                         Mark Scholz M.D. 
                         Stephen Strum M.D.  
                         June, 1995

Prostate Cancer Research Institute (PCRI)

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