Canada says "Warn the public" about Dutasteride and Finesteride

Thanks to Dan Zenka on the heads up of this article.

The REDUCE trial is not new news but rather the reaction by a state sponsored healthcare system is what I consider the big news. We have known that the occurrence of aggressive disease appears higher, but not necessarily true for men who prefer the ADT3 approach.

tinyurl.com/7ed5txe

Early use of Avodart and Proscar have been debated a long time in prostate cancer prevention. The REDUCE trial did not significantly prove that these agents worked that the FDA declined the requests by the manufacturers to be able to market them as such. These drugs treat BPH, and many prostate cancer patients swear, although without science on their side, that the agents need to be used when one goes on hormonal therapy. The fact is that we still do not have any definitive evidence based study proving this to be the case.

Take out of this what you will...

Tony

Tony, trying to understand the point being made here. Is it a good thing, or a bad thing? Could you simplify what is going on in layman's terms with these agents?

david

Ralph that is the big debate.

Did they prevent prostate cancer or simply skew PSA. In my opinion probably a bit of both. But those same studies showed that there was a noticeable increase in aggressive prostate cancer and if the trade off is that we detect less indolent prostate cancer but we increase the occurrence of aggressive prostate cancer then did we accomplish anything?

I'm not convinced we did. I don't see it...

Tony

I asked the Uro this question:

"is it possible that avodart reduced the size of the prostate and made it more likely that the tumor will "get out", because now it needs less growth to "get out"."

His response was - "no there is still an out shell, however it does help with biopsy.".

So, my answer has nothing to do with the aggressiveness, but want to add +1 to Ralph's answer on easy to detect in biopsy after a course of Avodart.

My med onc is certain that these drugs do not cause more aggressive PCa.   Rather they make it easier and earlier to find when it gives off little PSA.   By reducing the overall PSA there is a reduction in the PSA noise.   Then very subtle changes can be more pronounced and helpful in finding the more aggressive cancer that may be giving of very little PSA versus a low grade cancer.   To me that is a good thing.l   Plus as Ralph indicates, there is the factor that these meds will slow the development of cancer and is effective as a treatment by removing the high strength DHT that the other meds don't affect.

Hello Tony,
The topic was about the Canadian warning of the use of 5-AR inhibitors to prevent PCa. You just switched the topic. We were talking of PCa prevention and reducing the incidence of the disease and not survival If PCa is prevented or delayed in 25% of the men using these chemicals it follows that it must have some effect in survival (at this point unknown). Maybe not, but very possible and probable.

5-AR inhibitors do not mask PSA in a man known to have PCa. The effect of inhibiting dihydrotestosterone(DHT) will cause androgen dependent cells to die (both normal and cancerous) and this is the cause of prostate gland volume reduction in time of use. This is a biologic recognized effect and not masking.

Proscar and Avodart have a place in the prevention and treatment of PCa. These drugs are a milder form of hormone suppression and as such have an important place in treatment. To cast a shadow by a warning that is not yet supported by science is in detriment of the health of men . Beyond prevention, the major benefit of these DHT inhibitors is the prolongation of hormone suppression off-cycles. That alone is an improvement in patient's quality of life worth considering. In patients diagnosed with PCa who are on these inhibitors there is no PSA masking. The PSA reduction is valid because these inhibitors have an effect on PCa androgen dependent tumor cells by inducing cell death and the as such the PSA level is a true measurement of their disease.

For the results pf the PCPT trial on preventing PCa by 25% see:
www.ncbi.nlm.nih.gov/pubmed/14713747

For how the presence of more aggressive PCa in 5-AR inhibitors users has been invalidated by science see:

1: Klotz L. Words of wisdom. Re: Effect of dutasteride on the risk of prostate
cancer. Andriole G, Bostwick D, Brawley O, et al. N Engl J Med 2010;362:1192-202. Eur Urol. 2010 Aug;58(2):313. PubMed PMID: 20845544.

2: Klotz L, Drachenberg D, Fradet Y, Saad F, Trachtenberg J, Zlotta A. Gleason
grading controversies: what the chemoprevention trials have taught us. Can Urol
Assoc J. 2009 Jun;3(3 Suppl 2):S115-20. PubMed PMID: 19543430; PubMed Central PMCID: PMC2698786.

3: Kaplan SA, Roehrborn CG, Meehan AG, Liu KS, Carides AD, Binkowitz BS, Heyden NL, Vaughan ED Jr. PCPT: Evidence that finasteride reduces risk of most
frequently detected intermediate- and high-grade (Gleason score 6 and 7) cancer.
Urology. 2009 May;73(5):935-9. Epub 2009 Mar 28. PubMed PMID: 19328538.

4: Reed AB, Parekh DJ. The utility of 5-alpha reductase inhibitors in the
prevention and diagnosis of prostate cancer. Curr Opin Urol. 2009
May;19(3):238-42. Review. PubMed PMID: 19318950.

5: Redman MW, Tangen CM, Goodman PJ, Lucia MS, Coltman CA Jr, Thompson IM.
Finasteride does not increase the risk of high-grade prostate cancer: a
bias-adjusted modeling approach. Cancer Prev Res (Phila). 2008 Aug;1(3):174-81. Epub 2008 May 18. PubMed PMID: 19138953; PubMed Central PMCID: PMC2844801.

6: Lucia MS, Epstein JI, Goodman PJ, Darke AK, Reuter VE, Civantos F, Tangen CM, Parnes HL, Lippman SM, La Rosa FG, Kattan MW, Crawford ED, Ford LG, Coltman CA , Thompson IM. Finasteride and high-grade prostate cancer in the Prostate Cancer Prevention Trial. J Natl Cancer Inst. 2007 Sep 19;99(18):1375-83. Epub 2007 Sep 11. PubMed PMID: 17848673.

One more thought. We are all for preventing over treatment of PCa. Restricting the use of 5-AR inhibitors goes against a way to delay/prevent treatment. I feel strongly that the Canadian warning is premature and potentially damaging.

RalphV

Tony,
All I am saying is that the warning is overblown because there is evidence that the presence of more aggressive cancer in users was fictitious and not caused by 5-ARs.
In the meantime if better diagnosis are done earlier the probability of better response to specific treatments improves. Why screen with PSA if not to find those that need treatment? Better representative biopsies are key.

RalphV