Dutasteride and Prostate Cancer

[Old Baldy]

Here's a study indicating dutasteride can be used to TREAT prostate cancer.

I always thought finasteride. and/or dutasteride. could increase the chance of contracting high grade prostate cancer?

So, finasteride./dutasteride. can cause pre-cancerous cells to sometimes morph into high grade cancer cells but (1) finasteride./dutasteride. lowers the incidence of contracting cancer in the first place and (2) if you ALREADY have prostate cancer, dutasteride. (and probably finasteride.?) can help??!! WTF!!!!!!!!!!

As usual, I'm TOTALLY confused! :hairy:

I'm so sick and tired of studies that contradict themselves when it comes to finasteride./dutasteride. Maybe I'm just reading this stuff incorrectly?

Iczkowski KA, Qiu J, Qian J, Somerville MC, Rittmaster RS, Andriole GL, Bostwick DG. 2005 Jan;65(1):76-82
Department of Pathology and Laboratory Medicine, Veterans Affairs Medical Center, Gainesville, Florida 32608-1197, USA. iczkoka@pathology.ufl.edu

OBJECTIVES: To perform the first evaluation of the effects of the 5-alpha-reductase inhibitor class of drugs on cancer histopathologic features at radical prostatectomy in a placebo-controlled multicenter trial. METHODS: We analyzed prostatectomy slides in a blinded manner from 17 men treated with dutasteride, an inhibitor of types 1 and 2 isoenzymes of 5-alpha-reductase, and 18 men treated with placebo for 5 to 11 weeks before radical prostatectomy. The histopathologic features of benign epithelium, high-grade prostatic intraepithelial neoplasia, and cancer were recorded, and the treatment effect was scored. Digital imaging analysis was used to measure the stroma/epithelium ratio and epithelial height, as well as the nuclear area in cancer. RESULTS: In benign epithelium, treatment caused distinctive cytoarchitectural changes of atrophy and a decrease in the epithelial height (P = 0.053). The peripheral zone showed the most marked response to treatment. In cancer tissue, the tumor volume was significantly lower in the dutasteride-treated men than in the placebo-treated men (mean 15% versus 24%, respectively, P = 0.025), the percentage of atrophic epithelium was increased (P = 0.041), and the stroma/gland ratio was doubled (P = 0.046). The treatment alteration effect score was doubled (P = 0.055) and did not correlate with any Gleason score changes. CONCLUSIONS: After short-term dutasteride treatment, benign epithelium showed involution and epithelial shrinkage, and prostate cancer tissue demonstrated a decrease in epithelium relative to stroma. These findings indicate that dutasteride induces significant phenotypic alterations in both the benign and the neoplastic prostate, supportive of a chemopreventive or chemoactive role.

PMID: 15667867 [PubMed - indexed for MEDLINE]

Well, maybe the tumor shrinking effect of dutasteride. is better with dutasteride. than finasteride. due to the inhibition of the 5AR Type I enzyme? See the study posted by Kofi at alt.baldspot below:

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Date: Fri, Mar 5 2004 1:00 am
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Wonder if it has the same inhibitory effect on non-transformed androgen
receptors.

Prostate. 2004 Feb 1;58(2):130-44. Related Articles, Links
Click here to read
Dutasteride, the dual 5alpha-reductase inhibitor, inhibits androgen
action and promotes cell death in the LNCaP prostate cancer cell line.


Lazier CB, Thomas LN, Douglas RC, Vessey JP, Rittmaster RS.


Department of Biochemistry and Molecular Biology, Dalhousie
University, Halifax, NS, Canada.


BACKGROUND: Reduction of T to DHT by 5alphaR in the prostate
enhances androgenic activity for most targets. Inhibition of 5alphaR
activity with finasteride attenuates androgen action in men and animal
models. The objective of this study was to compare and contrast the
effects of a potent new 5alphaR inhibitor, dutasteride, with finasteride
in the LNCaP prostate cancer cell line. METHODS: LNCaP cells were
incubated for varying times with T or DHT in steroid-free medium in the
absence or presence of increasing doses of dutasteride or finasteride
and the effects on 5alphaR activity, PSA accumulation in the medium, and
on cell proliferation were determined. Drug effects on apoptosis were
investigated using Annexin V staining and a cell death ELISA assay.
Effects of the drugs on AR ligand-binding activity and on AR protein
levels were determined. RESULTS: Dutasteride inhibited (3)H-T conversion to (3)H-DHT and, as anticipated, inhibited T-induced secretion of PSA
and proliferation. However the drug also inhibited DHT-induced PSA
secretion and cell proliferation (IC(50) approximately 1 microM).
Finasteride also inhibited DHT action but was less potent than
dutasteride. Dutasteride competed for binding the LNCaP cell AR with an
IC(50) approximately 1.5 microM. High concentrations of dutasteride
(10-50 microM), but not finasteride, in steroid-free medium, resulted in
enhanced cell death, possibly by apoptosis. This was accompanied by loss
of AR protein and decreased AR ligand-binding activity. Occupation of AR
by R1881 partly protected against cell death and loss of AR protein.
PC-3 prostate cancer cells, which do not contain AR, also were killed by
high concentrations of dutasteride, as well as by 50 microM finasteride.
CONCLUSIONS: Dutasteride exhibited some inhibitory actions in LNCaP
cells possibly related to 5alphaR inhibition but also had antiandrogenic
effects at relatively low concentrations and cell death-promoting
effects at higher concentrations. Finasteride also was antiandrogenic,
but less than dutasteride. The antiandrogenic effects may be mediated by
the mutant LNCaP cell AR. Promotion of cell death by dutasteride can be
blocked, but only in part, by androgens. Copyright 2003 Wiley-Liss, Inc.


PMID: 14716738 [PubMed - indexed for MEDLINE

Until someone tells me otherwise, topical dutasteride. and finasteride. are NOW a part of my regimen! Some of that stuff will get into my bloodstream, that appears to be a good thing. Oh heck, I really don't know what to think any longer. :-x

I know it's "all about dosage" when it comes to drugs but I simply am as confused about this subject as is humanly possible.

About the only thing I'm NOT confused about is dutasteride./finasteride. can cause libido problems in men my age to a greater extent than in younger men. That's why I'm staying with topical use. Hopefully, the libido problems won't as likely occur. So far so good in this regard. Been about 2 weeks using topical dutasteride. and about 3 weeks using topical finasteride. (Not sure on time period but it's been recent for topical use of dutasteride./finasteride.)

 

[CCS]

there is no such thing as likely or unlike that sides occure with one person. they either do or they don't, and you will know in a month or so.

I did not understand how dutasteride has androgenic effects, meaning it competes for the androgen receptor to some extent. I'll have to find out what typical testosterone levels are, and would like to compare the concentration to that of dutasteride.

0.5mg/day gives (according to a graph i have) 32 ng/mL of dutasteride at steady state, and every other day is 16 and proscar each day is 7.

x1mol dutasteride/~500g x 1000mL/1L x 1g/1000000000 ng
x 1000000 u mol/1mol =

0.064 micro grams per liter. The doses in this trial are almost 1000 times that high. just don't take 1000 capsules per day and you should be fine.

I'm more concerned about the androgenic effects, which I think would be large only after all 5ar2 is gone, since after that you just have dutasteride floating around, which does look kind of like testosterone and could have an affinity for the receptor, though perhaps not as strong as testosterone or DHT.

at the very low dose of 0.064 micro moles per liter (molar means moles per liter), I doubt this occurs.

finally, the studies do not contradict each other. The first says it reduces cancers, and the second one says that at high doses, it kills healthy cells too, making them decentigrate into little peices. At least i think the cells were healthy. maybe those cells in the study were the cancer cells. that would be nice.

 

[Old Baldy]

They WERE the cancer cells!! The LNCaP cells are cancerous cells. dutasteride. killed them and made them androgen sensitive!!!! They usually become androgen independent and, that's when the cancer ADVANCES!!

http://mcr.aacrjournals.org/cgi/content ... ct/3/3/163

My reading makes me believe dutasteride. could be a "cure" for prostate cancer!!?? Well maybe not a cure but certainly a positive drug.

All this talk about finasteride. and dutasteride. advancing cancer is hogwash for the VAST majority of us IMHO. For the VAST majority of us it is a drug that DIMINISHES the chance of contracting cancer and once you have cancer it can KILL cancer cells.

I'm beginning to view finasteride. and dutasteride. as "high-tech", prostate, anti-cancer "vitamins".

Sorry Bryan and Dr. P, I think your both dead wrong on this one? Well I do admit there is a small chance of contracting a very agressive form of prostate cancer but that small percentage appears to be substantially outweighed by their cancer diminishing effects overall AND, their possible ability to kill cancer cells.

I'm honestly beginning to believe that finasteride. and dutasteride. will save many lives in the long run. Both young and old!! If I'm wrong please let me know.

 

[IDOASIS]

I'm honestly beginning to believe that finasteride. and dutasteride. will save many lives in the long run. Both young and old!! If I'm wrong please let me know.

You are not wrong.

Analysis Shows Drug Could Save Lives From Prostate Cancer

Atlanta 2005/02/28 -A new analysis shows the drug finasteride will save lives if given to men to prevent prostate cancer. Published in the April 1, 2005 issue of CANCER, a peer-reviewed journal of the American Cancer Society, the new analysis of data from the Prostate Cancer Prevention Trial (PCPT), says that any possible increase in the incidence of higher-grade tumors would be more than offset by an overall reduction in the number of prostate cancer cases in the general population.
The recent results from the PCPT represent a milestone in cancer research, showing that prostate cancer could be prevented through chemoprevention. The study found the commonly used drug finasteride reduced the incidence of prostate cancer by 24.8 percent compared to a placebo. However, a possible increase in the number of high-grade tumors in the trial prompted many to question whether any benefits of the drug would be offset by an increase in mortality related to the higher-grade tumors. No difference in mortality was seen during the 7 years of PCPT.

To explore the problem, Joseph M. Unger, M.S. and a team of researchers from the Southwest Oncology Group Statistical Center at the Fred Hutchinson Cancer Research Center in Seattle, WA analyzed Surveillance, Epidemiology, and End Results (SEER) registry data and applied the results from the PCPT.

The results showed a net reduction in person-years saved over ten years using finasteride even after taking into account an increase in high-grade cancers. Using PCPT’s 24.8 percent reduction in new cases, the drug would save 316,760 person-years over ten years. An absolute increase in 6.9 percent of cases with high-grade disease (the difference seen in the PCPT) would still mean 262,567 person-years saved.

Based on this model, the authors conclude, “even if finasteride is found to potentiate the growth of high-grade tumors, this analysis shows that the potential detrimental effects of an increased rate of cases with high grade Gleason score would be substantially outweighed by a reduction in incidence.â€￾





Article: “Estimated Impact of the Prostate Cancer Prevention Trial on Population Mortality,â€￾ Joseph M. Unger, Ian M. Thompson, Jr., Michael LeBlanc, John J. Crowley, Phyllis J. Goodman, Leslie G. Ford, Charles A. Coltman, Jr., CANCER; Published Online: February 28, 2004 (DOI: 10.1002/cncr.20919); Print Issue Date: April 1, 2005.

 

[Bryan]

Here's a study indicating dutasteride can be used to TREAT prostate cancer.

I always thought finasteride. and/or dutasteride. could increase the chance of contracting high grade prostate cancer?

So, finasteride./dutasteride. can cause pre-cancerous cells to sometimes morph into high grade cancer cells but (1) finasteride./dutasteride. lowers the incidence of contracting cancer in the first place and (2) if you ALREADY have prostate cancer, dutasteride. (and probably finasteride.?) can help??!! WTF!!!!!!!!!!

Sure, they can help for a while. But sooner or later, prostate cancer cells morph into a version that no longer requires androgens. By then, antiandrogenic therapies will no longer work. That process is probably SPEEDED-UP by such antiandrogenic therapies.

Until someone tells me otherwise, topical dutasteride. and finasteride. are NOW a part of my regimen! Some of that stuff will get into my bloodstream, that appears to be a good thing. Oh heck, I really don't know what to think any longer. :-x

As I've said so many times before, I think the timing is the critical issue here. The younger you are when you start taking those drugs, the better. Starting to take them when you're much older is a Journey Into the Unknown. The possible stimulation of high-grade tumors when you start taking them at our age may blunt the overall beneficial effect of such drugs.

Bryan

 

[Bryan]

They WERE the cancer cells!! The LNCaP cells are cancerous cells. dutasteride. killed them and made them androgen sensitive!!!!

Made them "androgen sensitive"? Huh??

They usually become androgen independent and, that's when the cancer ADVANCES!!

Well, more to the point, that's when antiandrogens and 5a-reductase inhibitors stop working.

My reading makes me believe dutasteride. could be a "cure" for prostate cancer!!?? Well maybe not a cure but certainly a positive drug.

Only if you start taking it early enough.

All this talk about finasteride. and dutasteride. advancing cancer is hogwash for the VAST majority of us IMHO. For the VAST majority of us it is a drug that DIMINISHES the chance of contracting cancer and once you have cancer it can KILL cancer cells.

If you start taking them early enough, prostate cancer will never become an issue. If you start taking them much later in life, things start to get very GRAY. Those drugs will only kill already-established cancer cells for a certain period of time.

Sorry Bryan and Dr. P, I think your both dead wrong on this one? Well I do admit there is a small chance of contracting a very agressive form of prostate cancer but that small percentage appears to be substantially outweighed by their cancer diminishing effects overall AND, their possible ability to kill cancer cells.

Again, I think the timing is profoundly important.

Bryan

 

[Aplunk1]

Bryan, are you suggesting that I'm benefiting from taking dutasteride at 21?

I say this because I have a LOOONG family history of prostate cancer and problems.

 

[Bryan]

Bryan, are you suggesting that I'm benefiting from taking dutasteride at 21?

I say this because I have a LOOONG family history of prostate cancer and problems.

Oh my god, you're an IDEAL candidate for dutasteride (or finasteride), in my opinion!! Keep taking it for the rest of your life!

Bryan

 

[Aplunk1]

Thanks, Bryan.

At first, I thought you were being really sarcastic.

I didn't know that I'd be benefiting in the long run for taking dutasteride...

Funny, my dad used to take dutasteride, but for a completely different reason.

 

[Bryan]

I'm serious as a heart attack. I would never be sarcastic about something this important. Just like how one study I've read mentioned that castration PRIOR to the age of about 40 will prevent the occurrence of prostate cancer later in life, but not AFTER the age of about 40, so too is the age that you start taking dutasteride or finasteride very important for that same purpose. In my opinion, of course.

Bryan

 

[Old Baldy]

I'm serious as a heart attack. I would never be sarcastic about something this important. Just like how one study I've read mentioned that castration PRIOR to the age of about 40 will prevent the occurrence of prostate cancer later in life, but not AFTER the age of about 40, so too is the age that you start taking dutasteride or finasteride very important for that same purpose. In my opinion, of course.

Bryan

Thanks for the info. in this quoted post and your response to my post above.

For men over 40, are there pre-cancerous cells existing that take years to develop into prostate cancer? If so, do you know the typical "incubation" period?

Btw, I agree 1 guzillion percent that young men taking finasteride./dutasteride. will probably NEVER contract prostate cancer.

Please explain in a little more detail, or point me to a study that explains why men over 40, when exposed to finasteride./dutasteride., can contract high grade prostate cancer. In other words, what's the friggin' mechanism.

I know you said "morph" into cancer cells. Where can I find an explanation on this subject? I'm not having much luck researching the internet. I'm just getting little snippets without much in the way of detailed explanations.

I know the chances are small when considering finasteride./dutasteride. can reduce the chance of contracting any type of prostate cancer more than it can increase the chance of contracting the high grade prostate cancer. However, the high grade cancer risk goes up by about 6.4 percent. That's small but still statistically significant isn't it.

Why this "old man" risk? Young men don't have pre-cancerous cells to any significant extent?

Thanks for any opinions and/or info.

 

[Old Baldy]

Idoasis: Thanks for posting the study, I didn't read it before posting my response to Bryan. It says high grade prostate cancer risk goes up by 6.9 percent.

Thanks again for posting the study.

 

[IDOASIS]

Idoasis: Thanks for posting the study, I didn't read it before posting my response to Bryan. It says high grade prostate cancer risk goes up by 6.9 percent.

Thanks for posting the study.

But you have missed my point.

Based on this model, the authors conclude, “even if finasteride is found to potentiate the growth of high-grade tumors, this analysis shows that the potential detrimental effects of an increased rate of cases with high grade Gleason score would be substantially outweighed by a reduction in incidence.â€￾

The results showed a net reduction in person-years saved over ten years using finasteride even after taking into account an increase in high-grade cancers.

finasteride and dutasteride can be life saving!

Concerning dutasteride ,it says high grade prostate cancer risk does not go up.

The treatment alteration effect score was doubled (P = 0.055) and did not correlate with any Gleason score changes

 

[Old Baldy]

Idoasis: Thanks for posting the study, I didn't read it before posting my response to Bryan. It says high grade prostate cancer risk goes up by 6.9 percent.

Thanks for posting the study.

But you have missed my point.

Based on this model, the authors conclude, “even if finasteride is found to potentiate the growth of high-grade tumors, this analysis shows that the potential detrimental effects of an increased rate of cases with high grade Gleason score would be substantially outweighed by a reduction in incidence.â€￾

[quote:382fa]The results showed a net reduction in person-years saved over ten years using finasteride even after taking into account an increase in high-grade cancers.

finasteride and dutasteride can be life saving!

Concerning dutasteride ,it says high grade prostate cancer risk does not go up.

The treatment alteration effect score was doubled (P = 0.055) and did not correlate with any Gleason score changes

[/quote:382fa]

Idoasis: I'm a layman. I swear that's how I read various studies but Bryan appears to disagree. I don't know as much as Bryan so I thought I read it wrong.

Could you please "pull out" the statement where the conclusion "dutasteride. doesn't cause high grade prostate cancer" is made. Remember I'm a layman. I came to that conclusion but can't "pull out that statement" now, I've forgotton what statement drove me to that conclusion.

But believe me, that was the main thrust of my posting throughout this thread.

Thanks for reinforcing that for me! dutasteride., with its reduction in 5AR Type I, appears to counter the high grade prostate contraction problem?

 

[IDOASIS]

Could you please "pull out" the statement where the conclusion "dutasteride. doesn't cause high grade prostate cancer" is made.

Gleason score -A system of grading prostate cancer. The Gleason grading system assigns a grade to each of the two largest areas of cancer in the tissue samples

The treatment alteration effect score was doubled (P = 0.055) and did not correlate with any Gleason score changes

It is from your first post.

 

[Old Baldy]

Could you please "pull out" the statement where the conclusion "dutasteride. doesn't cause high grade prostate cancer" is made.

Gleason score -A system of grading prostate cancer. The Gleason grading system assigns a grade to each of the two largest areas of cancer in the tissue samples

The treatment alteration effect score was doubled (P = 0.055) and did not correlate with any Gleason score changes

It is from your first post.

Thanks Idoasis! See how it is for an old layman!? :-x (I edited my first post and highlighted the phrase you quoted.)

What is it about dutasteride. that makes the results so much safer? (I know, another layman question, but make a guess.)

 

[Bryan]

For men over 40, are there pre-cancerous cells existing that take years to develop into prostate cancer? If so, do you know the typical "incubation" period?

That seems like a distinct possibility. Wouldn't want to guess about the "incubation period".

Please explain in a little more detail, or point me to a study that explains why men over 40, when exposed to finasteride./dutasteride., can contract high grade prostate cancer. In other words, what's the friggin' mechanism.

Nobody knows. It was just an observation in a medical journal article. But this general idea of "pre-cancerous" prostate cells years in advance of full-blown cancer seems quite plausible.

I know the chances are small when considering finasteride./dutasteride. can reduce the chance of contracting any type of prostate cancer more than it can increase the chance of contracting the high grade prostate cancer. However, the high grade cancer risk goes up by about 6.4 percent. That's small but still statistically significant isn't it.

Well, it can go up by more than that, depending on exactly what you mean by "6.4 percent". For example, if you have a certain medical problem in 1% of people who do NOT take a certain drug, and it rises to 2% in people who DO take a drug, you could say on one hand that the drug raises the incidence of the problem by 1 percentage point; on the other hand, you could say that the drug DOUBLES the incidence.

Why this "old man" risk? Young men don't have pre-cancerous cells to any significant extent?

Yes. That would seem to be the likely explanation.

Bryan

 

[Bryan]

The results showed a net reduction in person-years saved over ten years using finasteride even after taking into account an increase in high-grade cancers.

finasteride and dutasteride can be life saving!

Maybe, maybe not. In older men, I think it's more of a crap-shoot. But I think it's an OUTSTANDING strategy for very young men with a strong family history of prostate cancer, not to mention hair loss! :wink:

Concerning dutasteride ,it says high grade prostate cancer risk does not go up.

The treatment alteration effect score was doubled (P = 0.055) and did not correlate with any Gleason score changes

No, I wouldn't imagine it WOULD, over a period of only 1-3 months, and only 17 patients!

Bryan

 

[Bryan]

What is it about dutasteride. that makes the results so much safer?

Who sez dutasteride is any "safer" than finasteride?? The studies you posted on dutasteride were only short-term in vitro experiments showing that dutasteride has more potent antiandrogenic effects in prostate cancer cells than finasteride, which shouldn't exactly come as a huge surprise. However, that doesn't say anything about the central issue we're discussing here, which is the LONG-TERM use of such 5a-reductase inhibitors for the prevention of prostate cancer in men of all ages, and the bottom-line effect on mortality in each age group.

Bryan

 

[IDOASIS]

Thanks Idoasis! See how it is for an old layman!? :-x (I edited my first post and highlighted the phrase you quoted.)

No problem might

But I think it's an OUTSTANDING strategy for very young men with a strong family history of prostate cancer, not to mention hair loss! :wink:
Bryan

Agreed.

Concerning dutasteride ,it says high grade prostate cancer risk does not go up.

The treatment alteration effect score was doubled (P = 0.055) and did not correlate with any Gleason score changes

No, I wouldn't imagine it WOULD, over a period of only 1-3 months, and only 17 patients!

Bryan

Well ,true but that is all we have.

Another study is going on with Dutasteride to confirm it (if not finished by now).

5-alpha-reductase inhibitors are now in widespread use for the treatment of benign prostatic hyperplasia (BHP) and these molecules have recently come under the spotlight in prostate cancer. Their peripheral "hormonal" action inducing reduced intraprostatic DHT synthesis seems to involve them in this hormone-dependant disorder. Finasteride evaluated in the treatment of BPH (PLESS study) was found to have a preventive effect on the incidence of cancer and this activity was assessed in a specific trial (PCPT study). Nevertheless, in the latter randomized study with a 7-year follow-up period, a reduction in the global incidence of the number of cases of cancers was associated with an increase in the number of high-grade cancers. A slight reduction in prostate cancer was also noted in the studies with dutasteride in BPH (ARIA3001, ARIA3002 and ARIB3003). An international multicenter study (REDUCE) is currently being conducted to confirm the preventive value of this molecule which has a more complete activity than finasteride with its inhibitory action on the two 5-alpha-reductase iso-enzymes, and may therefore have a clearer efficiency and rule out the risk of onset of high-grade cancer.

I truly believe dutasteride is safer than finasteride as far as sides and cancer