5α-Reductase inhibitors and risk for high-grade prostate cancer


Yesterday the US Food & Drug Administration (FDA) updated its guidance on the use of 5α-reductase inhibitors with specific reference to the risk that use of these products may be able to induce high-grade (and therefore high-risk) prostate cancer in a small subset of men treated with these agents.

We should immediately be clear that the FDA is very cautious in its guidance, which includes the following statements:

  • “The Warnings and Precautions section of the labels for the 5-alpha reductase inhibitor (5-ARI) class of drugs has been revised to include new safety information about the increased risk of being diagnosed with a more serious form of prostate cancer (high-grade prostate cancer).”
  • This risk appears to be low, but healthcare professionals should be aware of this safety information, and weigh the known benefits against the potential risks when deciding to start or continue treatment with 5-ARIs in men.”
  • “5-ARIs may increase the risk of high-grade prostate cancer.”
  • “5-ARIs are not approved for the prevention of prostate cancer.”

[Editorial comment: Bold italic type in the above statements has been added for emphasis by The “New” Prostate Cancer InfoLink. The exact statements are taken from the FDA web site.]

The “New” Prostate Cancer InfoLink has commented extensively on the use of 5-ARIs (specifically finasteride and dutasteride and drugs containing these agents) and their supposed association with risk for induction of high-grade/high-risk prostate cancer in the past. We do not see the same level of risk associated with the use of these products as has been suggested by a small subgroup of physicians. However, we also do not think that the widespread use of 5-ARIs by primary care physicians for the prevention of prostate cancer is justified by the available data either.

We are concerned that the FDA has lost sight of the risk-benefit ratio associated with cancer prevention for men at high risk of prostate cancer in coming to the conclusions it has reached. However, we also appreciate the degree of political pressure that is now being placed on the FDA in the unreasonable belief that all drugs should be completely safe for clinical use by any physician. It has become extremely difficult for the FDA today to approve therapies that come with any perception of high-risk side effects if these drugs are being used to treat or to prevent disease in largely healthy men and women — or even a subset of those men and women who are at high risk of much more serious problems.

Since the 5-ARIs will continue to be available on the market for the treatment of disorders like benign prostatic hyperplasia and male pattern baldness, it is probably safe to assume that some specialists in the management of prostate cancer will continue to suggest use of these agents to carefully selected patients known to be at high risk for prostate cancer. This is probably the most appropriate use of the 5-ARIs in the prevention of prostate cancer anyway.

Drugs known to contain either finasteride or dutasteride are marketed in the USA under the following brand names: Proscar (finasteride/Merck), Avodart (dutasteride/GlaxoSmithKline), Jalyn (dutasteride + tamsulosin/GlaxoSmithKline), and Propecia (finasteride/Merck). Finasteride is also available as a generic agent since the loss of patent protection for use of this agent to treat men with symptoms of benign prostatic hyperplasia (BPH).

4 Responses

  1. Thanks for this wise and balanced perspective on the FDA’s action. I viewed the live webcast of the whole hearing on finasteride for prevention, and I came away appreciating the efforts by many leading doctors in favor of finasteride but discouraged by Dr. Patrick Walsh’s uninformed, unenlightened comments about the way these drugs work on DHT and also discouraged by what I thought was a heavy-handed approach by the FDA leadership at the hearing.

    As you note, the drugs are still available for prevention, and their best use is likely for patients at high risk of prostate cancer rather than an unaimed shot-gun approach at the broad population.

    I have been on finasteride continuously since September 2000 as part of my triple androgen deprivation therapy approach for a challenging case, which I have been able to do intermittently with great success.

  2. For some readers who may not be aware:

    There is a hypothesis that the observed increase in diagnosis of higher-grade prostate cancer in men taking 5-alpha-reductase drugs is not causative. Rather … these drugs shrink the prostate, making it easier to identify suspicious areas under ultrasound examination and consequently improving the accuracy in directing the biopsy needle.

    rd

  3. Here we go with physicians and patients going to read this FDA report and misunderstand its entire content. My medical oncologist has already asked what I think about this report. I gave him a long explanation that the FDA has not claimed that 5-ARIs cause high-grade prostate cancer. Rather, higher-grade prostate cancers were found because the 5-ARIs decreased the volume of the prostate gland, enabling better positioning of biopsy needles with resulting finding of higher-grade prostate cancer than when performing a biopsy on an enlarged gland.

    Here is a link to a commentary about this revision to the labeling of 5-ARIs that appears on the Medscape Oncology web site.

    Here is one part of the foregoing that all should read and heed:

    “However, a review of these findings published in 2009 in Clinical Cancer Research suggested that finasteride did not cause high-grade prostate cancers but simply made them easier to diagnose (Clin Cancer Res. 2009;15:4694-4699).

    ” ‘Our results suggest that the PCPT findings, in which finasteride use was associated with an increase in diagnoses of high-grade cancers, was likely the result of a detection bias rather than an increase in de novo high-grade prostate cancer,” study author Christopher Elliott, MD, PhD, a urology resident at Stanford University in California, told Medscape Medical News at that time. “These results would suggest that the fear of promoting high-grade prostate cancer with finasteride is likely unfounded.’ ”

    Read that last sentence again: “These results would suggest the fear of promoting high-grade prostate cancer with finasteride [and that would mean dutasteride as well] is likely unfounded.” That should have an exclamation point after it rather than a period.

    I expect our prostate cancer support lists are going to be occupied with patients questioning the use of 5AR inhibitors as the result of this statement from the FDA.

    That’s my opinion, and I’ll stand by it.

    Chuck

  4. OK, let me accept that the only consequence is that more cancers are detected earlier. That is of no consequence since there are no data to establish that early detection and primary treatment improve subsequent quality of life or all cause mortality.

    Given the risks of all prescription drugs, what are the remaining benefits?

    John

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

This site uses Akismet to reduce spam. Learn how your comment data is processed.

<span>%d</span> bloggers like this: