Avodart (dutasteride) & Proscar (finasteride)
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By: Mark Scholz, M.D.

Prostate Oncology Specialists

October 2010

Avodart® and Proscar® are FDA approved for the treatment of benign prostatic hyperplasia (BPH), the natural enlargement of the prostate that occurs with aging.  They are well-tolerated agents, except for occasional impotence or reduced libido that resolves when the treatment is stopped. Proscar and Avodart work by decreasing dihydrotestosterone (DHT) inside the prostate. DHT is five times more potent than testosterone. When the prostate is deprived of DHT, the gland shrinks. Reducing the size of the gland helps reverse a common symptom of prostate enlargement—slow urination. These drugs have an anti-cancer effect because cancer cells derived from the prostate are inhibited by low levels of DHT just like the normal cells of the prostate gland.

Proscar for Prostate Cancer

A study of over 18,000 men1 evaluated Proscar’s capacity to prevent prostate cancer. However, when the study was started the prevalence of microscopic Low-Risk prostate cancer was not fully appreciated. We now know that almost half of men in the United States over age 65 harbor microscopic prostate cancer. So instead of evaluating Proscar’s capacity to “prevent” prostate cancer, the study ended up evaluating Proscar’s ability to treat prostate cancer. After seven years of observation on Proscar, 10,000 of the men in the study underwent a prostate biopsy. The men treated with Proscar had 25% less cancers of the prostate than the men treated with placebo.

The men on Proscar also had 1% higher incidence of High-Risk prostate cancer, likely due to the fact that Proscar improved the accuracy of the PSA monitoring process making it easier to detect High-Risk disease. Unfortunately, when this information was made public, a famous urologist from Memorial Sloan Kettering named Peter Scardino, mistakenly concluded that Proscar caused High-Risk cancer.2 As implausible as this erroneous conclusion was, the impact of his editorial still lives on, being referenced to this day by people with a superficial understanding of this topic. Fortunately, subsequent letters to the editor and several subsequent articles strongly contradict this mistaken conclusion.3  Therefore, what we can conclude is that Proscar not only reverses cancer, it can improve the accuracy of the PSA monitoring process by enhancing the detection of High-Risk cancer.4

Avodart

The 5-alpha reductase enzyme that converts testosterone into DHT exists in three forms. Proscar blocks type II. However, type I is reported to occur more commonly in aggressive prostate cancer. Therefore Avodart, a medication which blocks both types I and II may be more effective. Just like Proscar, Avodart had been shown to reduce the risk of a prostate cancer diagnosis by about 22% in clinical trials.5,6 Unfortunately, Avodart and Proscar have never been studied in a head to head trial to determine if one is more effective than the other. However, studies do exist that show lower levels of DHT in the blood with Avodart compared to Proscar.

PSA Monitoring

Since both Proscar and Avodart lower PSA by about 50%, the question arises, “Are they masking the capacity of PSA to signal cancer progression?”  Briefly, the answer is no. These medications do not stop PSA from rising in men with progressive cancer. However, after starting Proscar or Avodart the PSA baseline does reset at a level 50% lower. For example, a man with a PSA of 6.0 before starting Proscar should drop to about 3.0 within a few months of starting Proscar. Subsequently, if the PSA rises consistently above 3.0, cancer progression should be entertained as a possible reason for the rise.7  In fact, since the 50% decline in PSA is fairly predictable, this decline can be considered a type of “stress test.” A failure for the typical 50% decline to occur raises the possibility of occult High-Risk disease.8

Other Applications

There are several ways the 5-alpha reductase inhibitors can be used. Men who have a family history of prostate cancer can take these agents to reduce their risk. Men on active surveillance may slow the rate of cancer progression. Lastly, Proscar and Avodart may improve outcomes when used in combination with other more potent testosterone inactivating pharmaceuticals such as Casodex®, Eulexin®, Lupron®, Zoladex® and ketoconazole.9

The rationale for concluding these anti-cancer agents are beneficial is based on the fact that no pharmaceutical drug eradicates or blocks testosterone completely. So the addition of a nontoxic 5-alpha reductace inhibitor to lower DHT as much as possible seems likely to be helpful. Studies do exist demonstrating the effectiveness of these agents in men with PSA relapsed disease where they delay the rise in PSA for a couple years.10 In another study, doubling of the “holiday period” was seen in men on intermittent hormone blockade.11

In terms of comparing the two agents, Proscar is less expensive. It also has a 20-year proven track record of being safe and effective. On paper, Avodart is more potent, but there are no head to head studies proving superior clinical efficacy.

Side Effects

A “good” side effect is the reversal of male-pattern baldness.  On the negative side, a minority of men will have a reduction in sex drive, difficulty getting an erection or in rare cases, breast enlargement. Treatment is usually stopped if any of these side effects occur. The side effects (except for breast enlargement) almost always reverse. A more consistent side effect is a reduction in semen volume which results from the reduced function of the prostate gland.

Conclusion

Proscar and Avodart have a meaningful therapeutic effect, generally with minimal side effects. They are user-friendly in that they don’t interact with other medications and can be taken anytime of the day with or without food. Proscar is available as a generic called finasteride and is very affordable. Given all these advantages, some doctors are considering their use in men who are yet to be diagnosed with prostate cancer to prevent the disease. While they may prove valuable in this capacity, we have found these agents to be more useful in the therapeutic sense, to treat prostate cancer after it has been diagnosed.

References

  1. Ian Thompson, The influence of finasteride on the development of prostate cancer. The New England Journal of Medicine, July 2003.
  2. Peter Scardino, The prevention of prostate cancer—The dilemma continues. The New England Journal of Medicine, July 2003.
  3. Claus Roehrborn, Prevention of prostate cancer with finasteride. The New England Journal of Medicine, October 2003.
  4. Ian Thompson, Effect of finasteride on the sensitivity of PSA for detecting prostate cancer. Journal of the National Cancer Institute, August 2006.
  5. Gerald Andriole, Effect of dutasteride on the detection of prostate cancer in men with benign prostatic hyperplasia. UROLOGY, 2004.
  6. Gerald Andriole, Further analysis from the REDUCE prostate cancer risk reduction trial. The Journal of Urology, April 2009.
  7. Gerald Andriole, 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
  8. Steven Kaplan, PSA response to finasteride challenge in men with a serum PSA greater than 4 ng/ml and previous negative prostate biopsy: Preliminary study. UROLOGY, 2002.
  9. Oliver Sartor, Activity of dutasteride plus ketoconazole in castration-refractory prostate cancer after progression on ketoconazole alone. Clinical Genitourinary Cancer, October 2009.
  10. Gerald Andriole, Treatment with Finasteride Following Radical Prostatectomy for Prostate Cancer, UROLOGY, 45: 491, 1995.
  11. Mark Scholz, Intermittent use of testosterone inactivating pharmaceuticals using finasteride prolongs the time-off period. The Journal of Urology, May 2006.