Effect of Avodart on PSA

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Aussie99
New Member


Date Joined Mar 2011
Total Posts : 5
   Posted 9/17/2011 5:21 AM (GMT -6)   
Hello everyone,

I'm hoping someone knows more about Avodart than me.

I was diagnosed almost 5 years ago with a 1 from 6 biopsy, 5% involvement and 3+3=6. PSA at diagnosis was 5.20 and prostate volume 93 cc.
A repeat biopsy 20 months later when PSA was 5.55, went 1 core from 20, also 3+3 and 5%. I have been doing active surveillance since then with 3 monthly PSA tests. The highest my PSA got was 6.83 in September, 2010.

With a large prostate, I have been having the expected urinary issues, so in January, 2011, I started on Avodart. PSA at that time was down slightly to 6.28. I was hoping for an improvement in urinary function and also the added benefit of a slowing in prostate cancer progression due to the blocking of testosterone conversion to dihydrotestosterone, which is alleged to be the main driver of cancer cell growth. I am also aware that Patrick Walsh believes that last statement not to be true.

All the information on Avodart advises to expect a PSA reduction of 40% after 4 months and 50% after 6 months and thereafter. I have not been able to find any clinical trial data where these percentages were established - it just gets stated everywhere. Anyhow, my personal experience is PSA down 22% after 4 months, and down 33% after 7.7 months, a much slower rate of reduction than the published data.

I had a look around the internet on forums and couldn't find much case history on the actual PSA reduction after commencing Avodart as a stand-alone therapy. But from the three cases I did find, only one man achieved a 50% reduction in PSA after 6 months. The second had a 29% reduction after 4.5 months and 46% after 9 months. The third bloke had an 18% reduction after 3 months, 24% after 6 months, 34% after 8.5 months and 51% after 11 months. This third case was a similar rate of PSA reduction to me. Has anyone reading this had a similar much slower rate of reduction in PSA ? I was trying to think of a reason for the slower rate of PSA reduction and wondered if Avodart caused more of a actual cc volume reduction with time rather than a percentage reduction in a particular time. That might explain why someone like me who started off with a really large prostate would experience a slower percentage rate of reduction on Avodart.

Also, what I am wondering is what is the reason that PSA goes down with Avodart. We know that Avodart causes a prostate volume to shrink and the conventional wisdom is that the PSA produced by a benign prostate is directly proportional to its volume. But they seem to say that Avodart only causes a 30% reduction in prostate volume, but a 50% reduction in PSA. So what causes the extra 20% reduction in PSA ? Does Avodart have the effect that not only does it reduce the size of a prostate, but also reduces the amount of PSA expressed per cc or gram of prostate tissue ?

And what effect does Avodart have on cancer cells other than the suggestion that it prevents the formation of dihydrotestosterone, the alleged villain ? Does Avodart also reduce the volume of prostate cancer cells in the same way that it reduces the volume of benign cells ? Does Avodart have any effect on the production of PSA from cancer cells, or is the PSA production from the cancer go on unchanged ? If PSA produced by the cancer is the same after taking Avodart, then it can be presumed that someone who has a significant proportion of their PSA coming from cancer cells, wont have a 50% reduction in PSA, but a lesser percentage due to their prostate volume reduction.

I would just like to get a better understanding of how Avodart works and any personal experience or other data would be really appreciated. Thanks.

Brian in Australia.

Carlos
Regular Member


Date Joined Nov 2009
Total Posts : 469
   Posted 9/17/2011 6:19 AM (GMT -6)   
Brian, I used finasteride to treat urinary symptoms from BPH.  I had about a 35% decrease in PSA and no improvement in urinary symtoms.  I stopped finasteride after several years and experienced a three fold increase in PSA about a year later. 
 
Here are a couple of links from the PCRI web site that may answer some of your technical questions.
 
Does Finasteride Alter the Pathology of the Prostate and Cancer Grading? http://www.prostate-cancer.org/pcricms/node/162.
 
Avodart (dutasteride) & Proscar (finasteride)   http://www.prostate-cancer.org/pcricms/node/439.
 
The first article was written by David G. Bostwick M.D., M.B.A., Bostwick Laboratories and the other by Dr. Scholz.
 
Carlos

Dx Feb. 2008, at age 71, PSA 9.1, G8, T1c
Eligard 3 mo. shot, Feb. 2008
daVinci surgery May 2008, G8(5+3), pT2c,N0,MX,R0
BCR 2 1/2 yrs after surgery
Salvage Radiation (IMRT), Dec. 2010 - Feb. 2011
PSA 0.10 seven months after IMRT, PSADT 8.6 months

JNF
Veteran Member


Date Joined Dec 2010
Total Posts : 1728
   Posted 9/17/2011 7:16 AM (GMT -6)   
The cancerous prostate cells can give off much more PSA than benign normal cells relative to their volume. As I recollect, the benign cells give off .66 PSA per cc and G6 give off either 3 or 4 PSA per cc. Thus, dimmenisioning the DHT can help shrink cancerous cells and have a greater proportionate PSA reduction than the shrinking of the benign cells. This reduction is less as the Gleason score increases so the effect is not as pronounced in someone with a higher Gleason.

As to the actual percentages and time frame that is going to vary amoung individuals as you are learning. Your reductions are easily within the range that would support the overall averages you have sighted. I view you PSA decreases in line with expectations so far, based on my understanding. What do your docs say?
PSA 59 on 8-26-2010 age 60. Biopsy 9-8-2010 12/12 positive, 20-80% involved, PNI in 3 cores, G 3+3,3+4,and 4+3=G7, T2b.
Eligard shot and daily Jalyn started on 10-7-2010.
IMRT to prostate and lymph nodes 25 fractions started on 11-8-2010
HDR Brachytherapy December 6 and 13, 2010.
PSA <.1 and T 23 on 2-3-2011.
PSA <.1 on 4-7-2011
Second Eligard shot on 4-7-2011
PSA <.1 and T <3 on 7-15-2011

jxmuldoon
Regular Member


Date Joined Nov 2009
Total Posts : 43
   Posted 9/17/2011 7:28 AM (GMT -6)   
Regarding your question about slow responses to finasteride or dutasteride, my psa took two years to halve, actually went up a bit 3 months after starting dutasteride, and did not decrease significantly for 18 months after starting dutasteride. Several biopsies show no malignancy or inflammation, but the doctors remain concerned. If you search for "finasteride challenge," you will find some inconclusive discussion on the issues.

Fairwind
Veteran Member


Date Joined Jul 2010
Total Posts : 2354
   Posted 9/17/2011 11:07 AM (GMT -6)   
Finasteride and dutasteride work great for men who do not have PC....But once PC is diagnosed, (as in your case) their ability to suppress PSA levels let alone cancer, vanishes and PSA levels can increase with frightening speed as the cancer progresses unhindered by these drugs..This seems to be especially true with the higher Gleason grades..
Age 68.
PSA age 55: 3.5, DRE normal.
age 58: 4.5
61: 5.2
64: 7.5, DRE "Abnormal"
65: 8.5, " normal", biopsy, 12 core, negative...
66 9.0 "normal", 2ed biopsy, negative, BPH, Proscar
67 4.5 DRE "normal"
68 7.0 3rd biopsy positive, 4 out of 12, G-6,7, 9
RALP Sept 3 2010, pos margin, one pos vesicle nodes neg. Post Op PSA 0.9 SRT, HT. 2-15-'11 PSA 0.0

az4peaks
Regular Member


Date Joined Feb 2011
Total Posts : 110
   Posted 9/19/2011 12:59 AM (GMT -6)   
Hi Aussie99, - Here in the U.S., the Manufacturer's printed Prescribing Instructions that is legally required to accompany the drug's prescription fulfillment include the following statements (at least some, if not all, required by our Federal Drug Administration) due to acknowledged Study results.

WARNINGS AND PRECAUTIONS ----------------

AVODART reduces serum prostate-specific antigen (PSA) concentration by approximately 50%. However, any confirmed increase in PSA while on AVODART may signal the presence of prostate cancer and should be evaluated, even if those values are still within the normal range for untreated men. (5.1)

AVODART may increase the risk of high-grade prostate cancer. (5.2, 6.1)

Assess patients to rule out other urological diseases, including prostate cancer, prior to prescribing AVODART. (5.3)

Women who are pregnant or could become pregnant should not handle AVODART Capsules due to potential risk to a male fetus. (5.4, 8.1)

Patients should not donate blood until 6 months after their last dose of AVODART. (5.5)

I am not sure that anyone completely understands the reasons for Avodarts reduction effect on PSA, EXCEPT that it is well established that the reduction in PSA that takes place with its use, is NOT proportionately due to reduction in Prostate size or ANY reduction in PCa tumor size. In fact the following statement is included as part of the required printed admonisions: "Limitations of Use: AVODART is not approved for the prevention of prostate cancer."

What IS clear, is that the doubling of PSA readings while on Avodart (after 3 to 6 months) is necessary, to provide accurate comparisons with readings when not on the drug and any increase while on the Avodart regimen, should specifically be assessed for a potential relationship to Prostate Cancer (PCa). Hope this helps and good luck in your continued AS. Remain vigilant! - John@newPCa.org (aka) az4peaks

jxmuldoon
Regular Member


Date Joined Nov 2009
Total Posts : 43
   Posted 9/19/2011 7:52 AM (GMT -6)   
I am unsure that az4peaks articulates a consensus view on doubling PSA score, after maintenance on Avodart, in order to get an accurate measure of PSA. Another view is that after six months on Avodart, one gets a new PSA baseline. Not all men see their PSA drop, and it is not clear that men who do not see a PSA drop have increased risk of malignancy.

Post Edited (jxmuldoon) : 9/19/2011 6:56:25 AM (GMT-6)


JNF
Veteran Member


Date Joined Dec 2010
Total Posts : 1728
   Posted 9/19/2011 9:47 AM (GMT -6)   
Additionally, some of the best oncologists, like Snuffy Meyers, keep men on Avodart/Procsar for long term maintenance after other ADT drugs have been stopped. The reduction of the DHT is important.
PSA 59 on 8-26-2010 age 60. Biopsy 9-8-2010 12/12 positive, 20-80% involved, PNI in 3 cores, G 3+3,3+4,and 4+3=G7, T2b.
Eligard shot and daily Jalyn started on 10-7-2010.
IMRT to prostate and lymph nodes 25 fractions started on 11-8-2010
HDR Brachytherapy December 6 and 13, 2010.
PSA <.1 and T 23 on 2-3-2011.
PSA <.1 on 4-7-2011
Second Eligard shot on 4-7-2011
PSA <.1 and T <3 on 7-15-2011
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