Finasteride and the Prostate Cancer Prevention Trial (PCPT)
Posted Sep 17 2008 1:25am
Waa … ayy back in the 1980s there was a lot of excitement in the research community about the potential of a new drug that was supposed to be able to shrink the size of men’s prostates as they grew older. That drug was finasteride (originally marketed in 1993 as Proscar for benign prostatic hyperplasia and later also as Propecia for treatment of male pattern baldness).
Anyway, in the early 1990s, Merck (the developers of finasteride) had another idea. If finasteride can shrink the size of a man’s prostate, and it is a very safe drug (which it certainly is), then maybe it can be tested as a drug to prevent the onset of prostate cancer!
The early trial results were promising, and in 1992 Merck partnered with the National Cancer Institute to develop and implement the Prostate Cancer Prevention Trial (PCPT) – the first major study of any drug or vaccine to attempt to prevent prostate cancer.
Between October 1993 and May 1997, PCPT enrolled 18,882 (mostly white) patients at centers in North America. The patients had to meet a small number of very specific criteria:
They had to be age 55 or older
They had to have general good health
They could have no evidence of prostate cancer at the beginning of the trial
Their prostate specific antigen (PSA) level had to be less than 3 ng/ml
They had to agree to have a prostate biopsy at the end of the study
The trial structure was very straightforward. The men were randomly assigned to take either 5 mg of finasteride or a placebo (dummy pill) once daily for 7 years. All the men had an annual digital rectal exam and prostate-specific antigen (PSA) test. At the end of the 7 years, all the men who had still not been diagnosed with prostate cancer would have a prostate biopsy to see if they were truly cancer free.
The trial was originally expected to run until at least 2004, but in June 2003 the PCPT was stopped early because of a clear finding that finasteride reduced the incidence of prostate cancer — by nearly 25 percent. So why isn’t every man in America over 55 now taking finasteride?
It turned out there was an immediate and unexpected problem. Among the trial participants who did develop prostate cancer while taking finasteride, there was a slightly higher incidence of high-grade tumors than was expected by chance.
In addition, it has since been shown that, because men taking finasteride have a reduced prostate size, they are at risk for higher-grade tumors on biopsy. Thirdly, researchers also found that high-grade cancer was detected earlier and in a less extensive stage in the finasteride group than in the placebo group.
Now it should be said that there are potential explanations for all three of these problem findings, and it is possible that finasteride really does prevent prostate cancer at minimal risk for patients. Here’s one “for example:”
If finasteride shrinks the prostate (and we know that it does), then whatever cancer is present in the prostate will be “more concentrated” than it would have been in men who didn’t take finasteride. Right? So if the cancer is more concentrated in men who take finasteride compared to men who take placebo, then you increase (a) the probability that a biopsy will “find” the cancer and (b) the possibility that the cancer you find will have a higher grade. It’s just common sense based on the probabilities. See also this on-line article by Scott Lucia et al., which addresses some of these complications of the results from the PCPT trial.
So where are we? Well, given the available data, everyone agreed that the risks associated with approving finasteride to prevent prostate cancer would be too high. (Just for starters, every man who got prostate cancer while taking finasteride to prevent prostate cancer would want to find a lawyer to sue on his behalf. After all, this America!)
The really important question today is, are there men who despite this risk have other risks that are so high that taking finasteride is still a good option for them? We have dealt with this on another page.
SELECT and several other major trials are also exploring the potential of drugs and vitamins as agents that might be used to prevent prostate cancer, and even more trials are definitely in development. In fact it is now possible that we will be able to significantly reduce risk for prostate cancer long before we find truly effective treatments for the disease that can eliminate the need for invasive therapy.