Thursday, March 17, 2011

Prostate Cancer Prevention: Is Avodart Friend or Foe?

Whenever I discuss prostate cancer prevention with my patients, the topic of  Avodart always comes up.  Avodart  ( Dutasteride is the generic name) is a hormonal medicine that is used to treat urinary symptoms associated with BPH (benign prostatic hyperplasia) in men with very large prostates.  It has been shown to work synergistically with another class of drugs called alpha blockers ( Hytrin, Cardura, Flomax) to help improve urinary symptoms and prevent urinary retention.  The way Avodart works is that it blocks an enzyme located in the prostate which converts the male hormone Testosterone to a more potent hormone Dihydrotestosterone.  By blocking this hormone, Avodart actually causes the glands of the prostate to shrink, allowing urine to more easily flow through it.

If Avodart is a medicine used to treat BENIGN enlargement of the prostate, why does it come up in conversations about prostate CANCER prevention?  The answer to that question comes in the form of a landmark study called the Prostate Cancer Prevention Trial which was published in the New England Journal of Medicine in 2003.  This study evaluated a drug similar to Avodart called Proscar (Finasteride is the generic name) in over 10,000 men.  The theory of the study was that the medicine can not only shrink normal glands in the prostate but also prostate cancer glands as well.  In so doing, the authors thought, Proscar could actually prevent small areas of prostate cancer in the prostate from growing and developing into full blown cancer.  The study had some groundbreaking and yet confusing results.  The authors demonstrated that taking Proscar could decrease the risk of prostate cancer by 25%.  This was truly an astounding discovery!  Unfortunately, however, it came with a catch.  The men who did get prostate cancer while taking Proscar were 27% more likely to have a more aggressive, life threatening form. 

The results of the Prostate Cancer Prevention Trial really put patients and urologists in a tough situation.  On one hand, Proscar significantly decreased the overall risk of prostate cancer.  On the other hand, however, those that did get prostate cancer got a more aggressive form.  Numerous theories were offered to explain these conflicting findings.  Some doctors argued that by shrinking the prostate, Proscar only helped to FIND the more aggressive prostate cancer on biopsies because the cancers were more noticeable with less benign prostate tissue around.  Others maintained that by shrinking the normal glands, Proscar allowed aggressive prostate cancer to grow without restriction in the prostate.  Taking all of this into account, experts finally recommended that men who have enlarged prostates that would benefit from Proscar from a urinary standpoint should still be offered the medicine.  In terms of prostate cancer prevention, however, the substantial benefits and risks meant that the medicine had to be considered on a patient by patient basis.

A few years after the Prostate Cancer Prevention Trial, a new medicine called Avodart was brought to market.  As I mentioned, this medicine, like Proscar, blocked the enzyme transforming Testosterone into a more potent compound called Dihydrotestosterone.  Avodart had the added advantage in that it blocked two forms of this enzyme as opposed to Proscar which only blocked one.  The theory is that Avodart may be more effective because of this additional enzyme which it blocks. Given this new drug, another large study was carried out to determine if it could prevent prostate cancer as well.  Called the REDUCE trial, the study compared the risk of cancer in over 3,000 men who took Avodart as compared to another 3000 similarly matched men who did not.  The study found that Avodart decreased the risk of Prostate Cancer by 23%.  In addition, over the 4 year course of the study, no difference in high grade, aggressive cancers was noted between the two groups.  Interestingly, however, in the last 2 years of the study, 12 of the patients taking Avodart developed prostate cancer as opposed to only 1 of the patients not taking it.  Once again, like Proscar, while Avodart appeared to reduce the overall risk of prostate cancer significantly, it appeared to also increase the chance that people who did get prostate cancer would have more aggressive variants. 

Recently, a request was made to the FDA for approval to market Avodart and Proscar for the indication of prostate cancer prevention.  The committee rejected the proposal unanimously.  They felt that the benefits of prostate cancer prevention did not outweigh the risks of at least potentially causing more aggressive prostate cancer in some patients.  So what is the take home message of all of this information?  Is it to tell you not to ever take Proscar or Avodart?  No. People who would benefit from it from a urinary standpoint should consider it.   The point of the post is simply to inform you that trying to prevent prostate cancer with these medicines is not a straightforward endeavor.  If your doctor recommends that you take these drugs solely to prevent prostate cancer, make sure you discuss these risks with him or her and are comfortable that they are worth taking.


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7 comments:

  1. What are urologists actually doing? Is anyone actually prescribing dutasteride or finasteride for chemoprevention, when it is not otherwise indicated for BPH / urinary symptoms? (I understand that would be off-label).

    You wrote, with respect to the REDUCE trial "it appeared to also increase the chance that people who did get prostate cancer would have more aggressive variants." Is that right? My reading of the REDUCE study suggested there was no statistically significant increase in high-grade cancers in the treatment group when compared to the control group (unlike in the PCPT study).

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  2. chamorgadol: I and most other urologists do not prescribe Dutasteride or Finasteride unless that patient has a large prostate and urinary symptoms for the reasons mentioned in the post.

    In the REDUCE trial there was no statistically significant increase in high grade cancers for those on Dutasteride if you look at the trial as a whole. However, if you look at the last 2 years of the study, 12 of the Dutasteride patients were found to have high grade cancers as opposed to only 1 of the placebo patients. It is this data that compelled the FDA to reject the application.

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