From: dittany@gmail.com (juniper)

"Drugs like Casodex and Flutamide, which allow testosterone to circulate
in the man's body while preventing it from docking in androgen
receptors"

Does it make a difference that there is testesterone in the system if it
can't connect anywhere?
=========

it makes a LOT of difference......

picture the androgen receptors like a lock and the testosterone like a
key that you put into the lock.  when this happens, the receptor gets
the hormone and the cancer is allowed to grow.

casodex is like taking a fake key - sticking it into the lock and
breaking it off - therefore - plugging up the lock and you can't get the
right key into the lock.

if the testosterone can't get into the key hole because the casodex has
plugged up the receptor, then, it slows down the overall cancer growth,
even if there is a lot of testosterone in the system.

~ curtis

knowledge is power - growing old is mandatory - growing wise is optional    
"Many more men die with prostate cancer than of it. Growing old is
invariably fatal. Prostate cancer is only sometimes so."
http://community.webtv.net/PALMER_ENT/doc

Hi Juniper...(Casodex or Flutamide) plus Proscar is practiced by some
men, typically those with a very slowly rising PSA after treatment.  T
is used throughout the body (in muscles for example) and so the
antiandrogen blocks the androgen receptors in these sites too.  I've
been told that while you don't feel quite as bad as when you're on
ADT3, you still feel pretty listless.  Another issue with this type of
therapy is that with "all that testosterone with nowhere to go", a lot
of it will aromatize to estradiol (E2).  Typically additional drugs are
need to prevent / lessen this transformation.  Whether this therapy
will lengthen the time to andgogen independence is anybody's guess...ron

It makes a difference to the man, but not to the cancer, theoretically.
Some skip ADT1, ADT2, and ADT3 (actually do an ADT3 minus ADT1) called BAC,
just so the man doesnt' have to go without testosterone.

Juniper,

This is a very good question, and the answer is fairly complicated and
technical.  To understand this, you have to put together lots of
different research.  For the sake of readability, I'll omit the
references for the research I'm about to discuss, but I'd be happy to
give you any reference that you want if you want to check something out
for yourself.

Basically, dealing with altering how hormones interact with  hormone
receptors is a double-edged sword.  It has the potential to almost wipe
out prostate cancer (PCa), or it can be fatal.  The exact same treatment
that is successful for one man may be disasterous for another.  Even
when a treatment works, it might wipe out 99% of the cancer cells, but
promote the other 1% to grow faster than ever.

The most important thing that you have to understand is that there are
two different androgen receptors - the intracellular one (iaR) and the
membrane one (mAR).  Casodex and Flutamide block iAR but have no effect
on mAR. Now, if your level of T drops below some critical level, then
you have ADT.  ADT works because mAR produces a protein, calreticulin,
which keeps PCa alive by preventing calcium overload apoptosis. Once T
falls below the critical level, not enough calreticulin is made and most
PCa cells tend to die - often before they get a chance to reproduce.

However, once your level of T goes above the level of ADT, then the
lower it is, the worse the prognosis.  Basically, they have shown that
men with the lowest levels of endogenous T are most likely to have PCa
cells that have escaped the prostate before treatment, and are most
likely to fail ADT.

It turns out that mAR also produces proteins that cause apoptosis.
Studies done where mAR was stimulated, but not iAR, show that apoptosis
occurs in all PCa cell lines tested, even in very aggressive
androgen-independent lines.  Studies with ADT have shown that PSA drops
to undetectable several months faster when 5mg/day of finasteride(F) is
given along with Casodex and a LHRH agonist than without the F.

From all of this, you might logically conclude that when using F and
Casodex, the higher the level of T the better. They have recently shown
that ADT followed by T and F is ~5 times more effective than continual
ADT.  Since DHT binds to iAR ~5 times stronger than T does, this showed
that just reducing the iAR activity while stimulating mAR activity was
sufficient to increase apoptosis greatly.  Adding Casodex to this
treatment should be even more effective.

A couple of obvious questions are what is the threshold level of T
necessary to get apoptosis to kill PCa faster than it grows, and what is
the upper level of T before you stop getting increased rates of
apoptosis.  Nobody has answered this question for T + F + Casodex, but
Dr. Leibowitz has reported that a T level of 1500 seems to be where PSA
declines when using just T + F.  It is likely that a lower threshold of
T would suffice with Casodex added as well.  There is no data on all on
the upper limit of T.  Dr. Leibowitz has observed that at a level of T
of 3500, the rate of decline in PSA is faster than it is at 1500, but he
never explored what the upper limit might be.

Also, people rightly pointed out the potential negative side effects of
T being converted to estradiol (E2).  This is readily corrected by
monitoring the level of E2 and using arimidex as needed to keep it
within the normal range.

Finally, although the above protocol may be effective for close to 100%
of men with PCa, there is always the possiblity of rare mutations that
can cause problems.  If, e.g., the man has a mutation that lost the mAR
totally, then Casodex by itself will cause the PCa to grow faster, and
Casodex plus F would cause it to grow faster still.  In this case you
can still wipe out the PCa by using T without the F or Casodex, but good
luck finding any doctor willing to utilize that treatment.  Even if you
did, you would have to closely monitor the PSA, since it is quite likely
that there would be some cells that would thrive under those conditions,
and you would have to switch to T + F + Casodex after wiping out all of
the PCa cells that lack mAR.

Also, adding T to Casodex + F could cause the PCa to grow faster if the
mAR is present but there is some rare mutation that affects its ability
to produce apoptotic proteins.  This can be countered with the proper
drugs, but they are not yet FDA approved, so there is no point in
discussing them here.

I apologize for the complexity of this post, but PCa is a complicated
disease.  About all anyone can do is to play the odds, while being aware
that random chance can give a fatal mutation to anyone at any time.

Ed Friedman