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Advodart or Proscar for the Treatment of Prostate Cancer
Avodart or Proscar for the Treatment of Prostate Cancer

Introduction and Background
Avodart (dutasteride) and Proscar (finasteride) are FDA-approved medications used to shrink the prostate gland in aging men who have a condition called benign prostatic hyperplasia (BPH). These medications are very well-tolerated and are usually devoid of side-effects. The most common side-effects, if any occur, are impotence or loss of libido. The risk of impotence or loss of libido is about 7%. The loss of libido and impotence reverse when the medications are stopped. These medications work by blocking an enzyme called 5-alpha reductase which converts testosterone into a much more potent form called dihydrotestosterone (DHT). In men, DHT is the major growth hormone of prostate cells. The prostate gland needs the ongoing presence of DHT to exist and proliferate. When the prostate is deprived of DHT it shrinks. These medications are popular for the treatment of BPH because they have the potential to reverse the problem of slow urination that can occur when the prostate enlarges.

Prostate cancer cells, which originate from the cells of the prostate gland, also need testosterone and DHT to grow and flourish. A number of medications for treating prostate cancer, such as Lupron, Zoladex, Eulexin, Casodex, and others, express their anti-cancer activity via some manner of testosterone-blocking. Avodart and Proscar are drugs that can limit the formation of testosterone in its most potent form, dihydrotestosterone; therefore they are also likely agents to inhibit the growth of prostate cancer.

Proscar for Prostate Cancer
Most studies of Proscar in prostate cancer have occurred in very advanced disease at a time when other cancer agents have already failed. Results of those studies demonstrated minimal benefit from Proscar. Proscar has also been used as a treatment in men who develop rising PSA levels after radical prostatectomy1. In this latter setting Proscar delays the rise of PSA for an average of one to two years.

Another much larger study of over 18,000 men was published in the New England Journal of Medicine in July of 2003.2 The goal of this study was to determine if Proscar could prevent the development of prostate cancer. Proscar was compared to placebo, and after seven years men treated with Proscar had a 25% reduction in the incidence of detecting new cancers of the prostate. Unfortunately an editorial by Dr. Peter Scardino in the same issue of the New England Journal of Medicine raised a concern that 1% of the men on Proscar developed a higher grade variant of prostate cancer. Dr. Scardino's unawareness of the previously known effect of Proscar to change the appearance of the cancer cells (but not change their aggressiveness) has led to much unnecessary confusion. Subsequent letters to the editor as well as a thorough review of the overall issue concluded that there is no evidence that Proscar induces higher grade forms of prostate cancer.3

Side Effects
We believe that one can conclude from these studies that Proscar clearly has anti-cancer activity. Are there any down sides to Proscar or Avodart? One concern is that Proscar lowers PSA by an average of 50%. Men with prostate cancer who are on watchful waiting monitor PSA to determine if there is any cancer growth. Does Proscar mask the ability of PSA to signal the progression of cancer? The short answer is no. Proscar resets the PSA baseline to a lower level but it does not stop the PSA from rising in men who have progressive disease. For example, take a man who has a PSA of 6.0 before starting Proscar. The PSA will drop by an average of 50% down to about 3.0. If the PSA rises to a notable degree above 3.0 this elevation indicates a need for further evaluation (with ultrasound, biopsy, MRI etc.) for signs of prostate cancer progression. This concept has been scientifically tested and proven in an article published in Urology in 1998.4

Application of Proscar
There are several logical ways to exploit Proscar's anticancer effects. The first is as a preventative agent in men who are at high risk (men with a positive family history for example). The second is as an inhibitory agent in men with small amounts of low grade disease who are pursuing a treatment plan called watchful waiting. Another name for this approach is close surveillance with deferred therapy. The third way Proscar can be used is to add it to other testosterone inactivating pharmaceuticals such as Casodex, Eulexin, Lupron, and Zoladex. We know that these agents, even when used in combination with each other, do not block all the testosterone from the body. So the addition of an additional nontoxic agent to further improve the blocking of DHT seems logical. Lastly Proscar slows the rate of PSA rise in men on intermittent hormone blockade. In our studies Proscar doubled the holiday period when compared to men who did not take Proscar.5

Avodart
The enzyme that Proscar blocks, 5- alpha-reductase, exists in two forms, type I and type II. Proscar only blocks the type I form, the form more common in the prostate gland. However the type II enzyme also exists in the prostate and it exists in higher concentration in the more aggressive types of prostate cancer. Glaxo, a pharmaceutical company has started marketing a competitor to Proscar called Avodart. Avodart blocks both type I and type II forms of the 5 alpha-reductase enzyme. If you ascribe to the theory that more complete blocking of DHT is superior to partial blocking of DHT, one might conclude that the newer agent, Avodart, will have a superior anticancer effect compared to Proscar. In our own practice at Prostate Oncology Specialists we have studied the levels of DHT in the blood in men on Proscar and subsequently switched to Avodart. Avodart almost always lowers the DHT level in the blood further than Proscar.

Andriole G. et al, Treatment with Finasteride Following Radical Prostatectomy for Prostate Cancer, Urology, 45: 491, 1995.
Thompson I. et al. The Influence of Finasteride on the Development of Prostate Cancer, NEJM 349:3; 213, 2003
Bostwick D. Does Finasteride Alter the Pathology of the Prostate and Cancer Grading? PCRI Insights, 7 2004
Andriole G. et al, Treatment with Finasteride Preserves Usefulness of Prostate-Specific Antigen in the Detection of Prostate Cancer: Results of a Randomized, Double-Blind, Placebo-Controlled Clinical Trial, Urology, 52:195, 1998
Scholz, M. et al, Intermittent Use of Testosterone Inactivating Pharmaceuticals using Finasteride (Proscar) during Testosterone Recovery Prolongs the Time Off Period. First Multidisciplinary Conference on Prostate Cancer Abstract #167