By Gary Schwitzer
In the sometimes Laurel-and-Hardy-like ("Here’s another fine mess
you’ve gotten us into!") interactions between industry, government, and
clinicians, there’s a debate brewing about whether drugs used to treat
benign prostate problems (BPH) should also be used to try to prevent
cancer of the prostate.
The drugs are of the class called 5-alpha reductase inhibitors (5-ARIs) -
drugs like finasteride (Proscar) or dutasteride (Avodart).
For more than two years the American Urological Association and the American Society of Clinical Oncology have recommended
that "healthy men who are screened regularly for prostate cancer and
show no symptoms of the disease should talk to their doctors about using
a 5-alpha reductase inhibitor (5-ARI) to prevent the disease."
Earlier this year, two drug companies making these drugs asked the
FDA to label their drugs as effective for cancer chemoprevention. Both
requests were resoundingly defeated at the advisory committee level.
Oncology Times reported:
"During
the wide-ranging discussion, several committee members expressed
concern about the possibility of widespread chemoprevention
prescriptions being written by varied practitioners for these drugs, and
about patients possibly influenced by direct-to-consumer advertising.
"It’s a little frightening, to be honest," said temporary voting member
Inger Rosner, MD, LTC, US Army Medical Corps, Urologic Oncologist at
Walter Reed Army Medical Center’s Urology Service."
The FDA accepted the advisory committee’s recommendation, and, in June, informed doctors
that that the labels for these drugs had 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)." In
other words, there was some evidence that these drugs that had been
proposed to prevent prostate cancers had actually been linked to more
aggressive prostate cancers in men who took them.
A physician friend wrote to me: "Questionable science led to a
questionable guideline that led to an aggressive marketing strategy that
backfired."
Interestingly, rather than refute that label change or the evidence behind it, the American Urological Association wrote to the FDA (pdf file) with concern about one line in the FDA statement:
"Prior to initiating therapy with 5-ARIs, perform
appropriate evaluation to rule out other urological conditions,
including prostate cancer, that might mimic benign prostatic hyperplasia
(BPH)."
The AUA countered:
"Because a biopsy is the most effective means by which
we can distinguish malignant from benign disease, the current wording
implies that all men obtain a routine prostate biopsy prior to
commencing treatment — something that is, at present, not supported by
the literature."
Or, another view would be that all men should think really carefully
before even considering treatment with this drug — which was the point
of the FDA labeling action.
An article in the Journal of General Internal Medicine* in January concluded that:
"If reducing prostate caner incidence without regard to
mortality is the desired outcome, forgoing PSA screening in the first
place would be a much more effective strategy."
Of course, the entire issue may be a moot point depending on what
goes on behind urologists’ office doors when they meet with men, since,
as a New England Journal of Medicine perspective piece by FDA authors stated last month:
"There is clearly ongoing off-label use of 5 alpha reductase inhibitors for this indication."
It will be interesting to see how the FDA responds.
* Dr. Michael Barry, one of the authors of the JGIM piece, is president of the Foundation for Informed Medical Decision Making, which supports the HealthNewsReview.org project. Dr. Richard Hoffman, another of the authors, is one of the project’s medical editors.