VERY IMPORTANT! Prevent "FLARE" Before Beginning or Returning to Androgen Deprivation Therapy (ADT)
By Charles C. Maack (Prostate Cancer survivor and active participant in the Wichita
Chapter - Us TOO)
In discussions with prostate cancer survivors or continuing prostate cancer
patients at our monthly Wichita Chapter Us TOO Intl., Inc. Prostate Cancer
Education and Support Group meetings, many men who were administered
androgen deprivation therapy were done so without the physician first
considering the prevention of "flare." In that context, the following information is as
important to the patient as it is to the urologists and/or oncologists who
administer androgen deprivation therapy.
Remarks by Dr. Stephen E. Strum, a internationally renowned Medical
Oncologist Specializing in Prostate Cancer in physician to patient Email
exchanges:
In commenting about urologists and oncologists failing to administer an
anti-androgen for a week to prevent clinical or biochemical "flare" prior to
beginning an initial injection of Lupron or Zoladex: "Above all do no harm
is what we are taught." By not acting to prevent flare "we have a major
chance to do harm." "We can't be ignoring pharmacology in our therapy. We
lose 100,000 Americans each year to fatal drug side effects. We have
millions more who are injured by adverse effects that are non-fatal but
still cause major morbidity. This also amounts to billions of dollars in
healthcare costs.
We must understand pharmacology and adverse effects to the drugs we
prescribe.
If you have the tools in your toolbox, use them appropriately but don't
drill a hole in your abdomen instead of the wall."
Dr. Strum also remarks:
"ADT (androgen deprivation therapy) should:
1) NOT be started with monotherapy with Lupron or Zoladex since biochemical
and possibly clinical flare will occur. Instead, ideally an anti-androgen
such as Flutamide or Casodex should be started 7 days before Lupron or
Zoladex is given. Moreover, we use an additional agent to block DHT
production. Such an agent is either Avodart or Proscar. DHT is 5 times as
potent in stimulating PC growth as is Testosterone (T).
2) Baseline studies should also be done first to include PAP (Prostatic Acid
Phosphatase) & testosterone level at the very least. Here is a comment on
flare (covered in depth in "A Primer on Prostate Cancer - The Empowered
Patient's Guide" authored by Dr. Strum and Donna Pogliano)The Importance of Preventing Flare
The anti-androgen should be administered at least 7 days prior to the LHRH
agonist. This is done to prevent or diminish the effects of initiating the
LHRH agonist which routinely results in release of LH, stimulation of
gonadal testosterone and increased growth of PC with release of PSA. The
cell populations that are stimulated involve both benign and malignant
prostate cells.
In patients with bulky disease that is compromising spinal cord, ureters,
or seriously involving bone, this paradoxical stimulation at the start of
LHRH therapy can result in medical emergencies such as spinal cord
compression, ureteral blockade or severe increase in bone pain. Even in
patients without bulky disease, we have detected increases in LH,
Testosterone and PSA despite using 7 days of an anti-androgen. However,
even though the PSA does increase, this effect is markedly dampened by the
priming doses of anti-androgen which results in a fall in PSA within 24
hours. Therefore, the anti-androgen prevents testosterone released during
the initial surge from the LHRH agonist from doing major damage. We call
this biological flare as contrasted with clinical flare. Biological flare
is characterized by an increase in LH, testosterone and PSA whereas clinical
flare is associated with the same plus clinical symptoms of an increasing
tumor mass.
Since there are studies showing that PSA in itself leads to tumor growth by
cleaving Insulin Growth Factor 1(IGF-1) from Binding Protein 3 resulting in
free IGF-1, a potent stimulator of tumor cell growth, we feel that any
maneuver that will decrease PSA may be of benefit to the patient. PSA will
also cleave the pro-molecule of urokinase plaminogen activator (uPA) to the
high molecular weight uPA or HMW-uPA. uPA is made by the PC cell and also
stimulates its own growth (autocrine effect). uPA dissolves bone matrix by
its activating collagenase I and releases IGF-1 by cleaving IGF binding
proteins 1 & 2. uPA also stimulates the osteoblast to grow and release other
active growth factors. Anything that we can do to stop these autocrine and
paracrine cycles may help the man with PC.
Preventing tumor flare is therefore a good first step.
I use Flutamide to prevent flare since it has a SHORT half-life measured in
hours ( 8 hours) as opposed to Casodex which has a half life measured in
days (6 days). I want a short time to a steady state blood level (32 hours
or four half lives with Flutamide) vs a long time (37 days or 6 half lives
with Casodex) if I am only going to have 7 days to prevent flare."
In several email comments to patients and in "A Primer on Prostate Cancer,"
Dr. Strum validates the efficacy of ADT prior to RT, Cryotherapy,
Brachytherapy, et al to reduce the volume of the prostate gland to better
respond to these therapies, as well as to determine whether or not the PC is
androgen dependent. He notes that first using ADT and having a major
reduction in the prostate gland CA will give RT a much better chance of
responding. RT is VOLUME DEPENDENT on obtaining excellent results. If the
volume is too large, then RT will not eradicate all the PC and cancer will
grow within an irradiated field.
If you do not own a copy of by Stephen E. Strum, M.D., a Medical Oncologist Specializing in Prostate Cancer and Donna Pogliano, IT IS ABOUT TIME YOU PURCHASE ONE!
