Re: Vantas versus Zoladex

[Guest guest]

> DAVID COLLINS

>

> From todays papers:

>

>> " A pioneering treatment that improves the lives of prostate

>> cancer sufferers has just been launched in the UK.

>> ...

>> Mr Raj Persad, Consultant Urologist at Bristol Urology

>> Associates and a prostate cancer specialist, says: 'Each time

>> a patient has an injection in his stomach he gets a flare of

>> testosterone, which is what we're trying to reduce.

>>

>> 'This flare may be problematic and cause a worsening of

>> symptoms. Vantas patients don't have repeated injections, so

>> this doesn't occur in the first place.'

>

> Fellas,

>

> I take much of what I read about PCa with a pinch of salt, but

> this article intrigued me. I was unaware that there were

> testosterone flares with monthly or quarterly (12 weekly)

> Zoladex jabs, other than with the first jab when, at least in

> the UK, we're given 28 days of Cyproterone, ie 14 days either

> side of the first jab, to deal with the flare issue. If there

> are flares associated with regular Zoladex jabs then presumably

> there are effects on PSA readings. Thus, if quarterly PSA

> readings are taken (as in my case) they will not necessarily

> occur at at the same time in the 12 weekly Zoladex cycle.

> Might this account for some variability, even PSA bounce?

> Again, what if the medical practice cocks up and misses one of

> the regular 12 weekly jabs, as mine did recently so that I

> missed 3 weeks of " cover " (my fault for trusting them and not

> keeping a check myself), what might this do to the PSA reading?

> I shall find out in a couple of weeks!

>

> Do any of our colleagues in the US have any experience of

> Vantas? Is what is claimed in the article true? Any informed

> opinions about this treatment?

>

>

,

It sounds like BS to me. My understanding of the way an LHRH

agonist works is that it stimulates production of a hormone which

in turn stimulates the production of testosterone. The testes

start producing testosterone around the clock. After about a

week of that, the testes shut down from overload and stop

producing testosterone. As long as they keep receiving the

leutenizing hormone stimulated by the drug, they stay shut down.

The 3 month injections of Lupron, Trelstar, Zoladex, Eligard, or

whatever are intended to be renewed _before_ the drug stops

working, not after it stops. As I understand it, there should be

NO testosterone flare from the second and subsequent injections

because the drug administered in the previous injection has not

yet worn off.

As evidence of this, ask anyone who has had intermittent hormone

therapy, or has finished a course of HT. In my case, my last

Lupron injection was a 3 month dose. But tests of my

testosterone levels, as well as my own subjective sense of when

the effects wore off (hot flushes ended, libido returned, etc.)

were that it was in the fifth month after the injection that

testosterone began to come back and at least the sixth before it

was back to normal. I was told that this is the normal case.

A 12 month injection sounds to me like a significant convenience

for some men, though one has to be careful with it. If it turns

out that the drug is doing damage, for example liver damage,

which is not uncommon with at least some LHRH agonists, you want

to be able to get off and try something else, for example a

different LHRH agonist, or a drug like Casodex. Having a 12

month implant gives you no options for a full year - unless

there's some way to remove it, which doesn't sound like an

attractive procedure.

Alan

[Guest guest]

I have monthly Zoledex as I believe that the side effects are less

eg I don't suffer mood swings

I had Casodex (Bicultamide) before taking Zoledex and alongside it for a few weeks

I understand that Casodex molecules fit to Testosterone molecules like jigsaw pieces - thus blocking the Testosterone's action

Re: Vantas versus Zoladex

> DAVID COLLINS <sirenettabtinternet>> > From todays papers:> >> "A pioneering treatment that improves the lives of prostate>> cancer sufferers has just been launched in the UK.>> ...>> Mr Raj Persad, Consultant Urologist at Bristol Urology>> Associates and a prostate cancer specialist, says: 'Each time>> a patient has an injection in his stomach he gets a flare of>> testosterone, which is what we're trying to reduce.>> >> 'This flare may be problematic and cause a worsening of>> symptoms. Vantas patients don't have repeated injections, so>> this doesn't occur in the first place.'> > Fellas,> > I take much of what I read about PCa with a pinch of salt, but> this article intrigued me. I was unaware that there were> testosterone flares with monthly or quarterly (12 weekly)> Zoladex jabs, other than with the first jab when, at least in> the UK, we're given 28 days of Cyproterone, ie 14 days either> side of the first jab, to deal with the flare issue. If there> are flares associated with regular Zoladex jabs then presumably> there are effects on PSA readings. Thus, if quarterly PSA> readings are taken (as in my case) they will not necessarily> occur at at the same time in the 12 weekly Zoladex cycle.> Might this account for some variability, even PSA bounce?> Again, what if the medical practice cocks up and misses one of> the regular 12 weekly jabs, as mine did recently so that I> missed 3 weeks of "cover" (my fault for trusting them and not> keeping a check myself), what might this do to the PSA reading?> I shall find out in a couple of weeks!> > Do any of our colleagues in the US have any experience of> Vantas? Is what is claimed in the article true? Any informed> opinions about this treatment?> > ,It sounds like BS to me. My understanding of the way an LHRHagonist works is that it stimulates production of a hormone whichin turn stimulates the production of testosterone. The testesstart producing testosterone around the clock. After about aweek of that, the testes shut down from overload and stopproducing testosterone. As long as they keep receiving theleutenizing hormone stimulated by the drug, they stay shut down.The 3 month injections of Lupron, Trelstar, Zoladex, Eligard, orwhatever are intended to be renewed _before_ the drug stopsworking, not after it stops. As I understand it, there should beNO testosterone flare from the second and subsequent injectionsbecause the drug administered in the previous injection has notyet worn off.As evidence of this, ask anyone who has had intermittent hormonetherapy, or has finished a course of HT. In my case, my lastLupron injection was a 3 month dose. But tests of mytestosterone levels, as well as my own subjective sense of whenthe effects wore off (hot flushes ended, libido returned, etc.)were that it was in the fifth month after the injection thattestosterone began to come back and at least the sixth before itwas back to normal. I was told that this is the normal case.A 12 month injection sounds to me like a significant conveniencefor some men, though one has to be careful with it. If it turnsout that the drug is doing damage, for example liver damage,which is not uncommon with at least some LHRH agonists, you wantto be able to get off and try something else, for example adifferent LHRH agonist, or a drug like Casodex. Having a 12month implant gives you no options for a full year - unlessthere's some way to remove it, which doesn't sound like anattractive procedure.Alan

[Guest guest]

,

From medicine online.com

Vantas Implant

DESCRIPTION

Vantasâ„¢ (histrelin implant) is a sterile non-biodegradable, diffusion-controlled reservoir drug delivery system designed to deliver histrelin continuously for 12 months upon subcutaneous implantation. The Vantas implant contains 50 mg of histrelin acetate. Histrelin acetate is a synthetic nonapeptide analogue of the naturally occurring gonadotropin releasing hormone (GnRH) or luteinizing hormone releasing hormone (LH-RH). The sterile Vantas implantation device (provided with the implant) is used to insert the implant subcutaneously in the inner aspect of the upper arm. After 12 months, the implant must be removed. At the time the implant is removed, another implant may be inserted to continue therapy.

The sterile Vantas â„¢ implant consists of a 50-mg histrelin acetate drug core inside a non-biodegradable, 3 cm by 3.5 mm cylindrically shaped hydrogel reservoir (Figure A). The drug core also contains the inactive ingredient stearic acid NF. The hydrogel reservoir is a hydrophilic polymer cartridge composed of 2-hydroxyethyl methacrylate, 2-hydroxypropyl methacrylate, trimethylolpropane trimethacrylate, benzoin methyl ether, Perkadox-16, and Triton X-100. The hydrated implant is packaged in a glass vial containing 2.0 mL of 1.8% NaCl solution. The implant is primed for release of the drug upon insertion.

Of 138 patients who received an implant, one discontinued prior to Day 28 when the implant was expelled on Day 15. Three others did not have an efficacy measurement for the Day 28 visit. Otherwise serum testosterone was suppressed to below the castrate level (≤50ng/dL) in all 134 evaluable patients (100%) on Day 28. All three patients with missing values at Day 28 were castrate by the time of their next visit (Day 56).

Of 120 patients who completed 52 weeks of treatment, a total of 115 patients had a serum testosterone measurement at Week 52. Of these, all had serum testosterone ≤50ng/dL. In patients without a Week 52 value, castrate levels were achieved by Day 28, were maintained up to Week 52, and remained below the castrate threshold after Week 52.

In all 18 patients who prematurely discontinued prior to Week 52 – except one (implant expulsion on Day 15) –castrate levels of serum testosterone were achieved by Day 28 and were maintained up to and including the time of withdrawal.

A total of 113 patients had a new implant inserted for a second year of therapy following removal of the first implant. Of this group, 68 patients had measurement of serum testosterone on Day 2 or Day 3 and on Day 7 after insertion of the second implant in order to assess for the "acute-on-chronic" phenomenon. No acute increase in serum testosterone was seen in any patient in this group following insertion of the new implant.

Serum prostate specific antigen (PSA) was monitored as a secondary endpoint. Serum PSA decreased from baseline in all patients after they began treatment with Vantas. Serum PSA decreased to within normal limits by Week 24 in 103 of 111 evaluable patients (93%).

Of 120 patients who completed 52 weeks of treatment, a total of 115 patients had a serum testosterone measurement at Week 52. Of these, all had serum testosterone ≤50ng/dL. In patients without a Week 52 value, castrate levels were achieved by Day 28, were maintained up to Week 52, and remained below the castrate threshold after Week 52.

In all 18 patients who prematurely discontinued prior to Week 52 – except one (implant expulsion on Day 15) –castrate levels of serum testosterone were achieved by Day 28 and were maintained up to and including the time of withdrawal.

A total of 113 patients had a new implant inserted for a second year of therapy following removal of the first implant. Of this group, 68 patients had measurement of serum testosterone on Day 2 or Day 3 and on Day 7 after insertion of the second implant in order to assess for the "acute-on-chronic" phenomenon. No acute increase in serum testosterone was seen in any patient in this group following insertion of the new implant.

Serum prostate specific antigen (PSA) was monitored as a secondary endpoint. Serum PSA decreased from baseline in all patients after they began treatment with Vantas. Serum PSA decreased to within normal limits by Week 24 in 103 of 111 evaluable patients (93%).

I hope this helps.

Mike C.

Subject: Vantas versus ZoladexTo: ProstateCancerSupport Date: Tuesday, April 6, 2010, 4:52 PM

From todays papers:

"A pioneering treatment that improves the lives of prostate cancer sufferers has just been launched in the UK.

About 35,000 men are diagnosed with prostate cancer each year in the UK and more than 10,000 die from the disease.

While current treatments involve injections of synthetic hormones into the stomach every one or three months, which can be painful, the Vantas implant lasts up to a year.

Inserted under the skin, the implant contains a synthetic hormone - histrelin - which lowers testosterone. Reducing the amount of testosterone in the body can slow the growth of the tumour by many years.

Like other hormone treatments, Vantas also significantly reduced PSA levels (a marker for the disease) by the second week of treatment.

The use of histrelin - a luteinising - hormone-releasing hormone (LHRH) agonist - has become a standard option for men with advanced prostate cancer.

Vantas is different from other LHRH agonists in that it releases histrelin gradually for up to 12 months, compared to other treatments that have a maximum duration of three months.

One of the main benefits to this slow release is that it prevents testosterone levels flaring - which is better for long-term prognosis.

Mr Raj Persad, Consultant Urologist at Bristol Urology Associates and a prostate cancer specialist, says: 'Each time a patient has an injection in his stomach he gets a flare of testosterone, which is what we're trying to reduce.

'This flare may be problematic and cause a worsening of symptoms. Vantas patients don't have repeated injections, so this doesn't occur in the first place.'

In the past, the treatment for men with advanced prostate cancer would often involve removal of the testes.

However, during clinical trials, Vantas was shown to be just as effective at suppressing testosterone levels after four weeks' treatment. It also maintained these levels in patients during 52 weeks of therapy.

After 12 months, the implant is removed and, if treatment is to be continued, another implant may be inserted at the same time as removal.

Vantas has been offered to men in the U.S. for five years and has been available on the NHS since last January.

Porta, of the male cancer charity Orchid, said: 'We welcome new treatment options, especially those which can offer patients an improved quality of life.'

Mr Raj Persad, who has treated two of the first Vantas patients in the UK, says: 'A patient's quality of life is just as important as their life expectancy and it can be very stressful and time consuming going to hospital for regular injections.

'Vantas is all about patient lifestyle choice and the benefits of a onceyearly procedure versus multiple injections.

'It is suitable for patients with advanced prostate cancer, whether they are new to hormone therapy or on an existing treatment.'

Read more: http://www.dailymai l.co.uk/health/ article-1263830/ Implant-ends- misery-prostate- jabs.html# ixzz0kM2AQBmN"

Fellas,

I take much of what I read about PCa with a pinch of salt, but this article intrigued me. I was unaware that there were testosterone flares with monthly or quarterly (12 weekly) Zoladex jabs, other than with the first jab when, at least in the UK, we're given 28 days of Cyproterone, ie 14 days either side of the first jab, to deal with the flare issue. If there are flares associated with regular Zoladex jabs then presumably there are effects on PSA readings. Thus, if quarterly PSA readings are taken (as in my case) they will not necessarily occur at at the same time in the 12 weekly Zoladex cycle. Might this account for some variability, even PSA bounce? Again, what if the medical practice cocks up and misses one of the regular 12 weekly jabs, as mine did recently so that I missed 3 weeks of "cover" (my fault for trusting them and not keeping a check myself), what might this do to the PSA reading? I

shall find out in a couple of weeks!

Do any of our colleagues in the US have any experience of Vantas? Is what is claimed in the article true? Any informed opinions about this treatment?

[Guest guest]

Metcalf wrote:

> I understand that Casodex molecules fit to Testosterone

> molecules like jigsaw pieces - thus blocking the Testosterone's

> action

More precisely, from the Wikipedia article on bicalutamide

(the generic name for Casodex):

" Bicalutamide acts as a pure anti-androgen by binding to the

androgen receptor (AR) and preventing the activation of the

AR and subsequent upregulation of androgen responsive genes

by androgenic hormones.[7][8] In addition, bicalutamide

accelerates the degradation of the androgen receptor.[9] "

Hormones, including testosterone, are signaling molecules.

They're like little messages sent out from the gland that

produces them to other cells in the body that receive them and do

something different when they do.

My understanding is that prostate cells have testosterone

" receptors " , which are molecules inside the cell that have a

shape (physical and electrical) that fits the testosterone

molecule. When T is absorbed into the cell, it binds to these

receptors and the complex of T + receptor causes the chemical

changes that the cancer cells need. Bicalutamide has one surface

that also fits the receptor and, in effect, takes it out of

action. The surface of the receptor that fits the testosterone

is plugged up. If we think of the receptor as a lock and

testosterone as a key that fits it, bicalutamide is chewing gum

that plugs up the lock so the key won't fit.

Alan

[i love molecular biology]

[Guest guest]

Clowes wrote:

....

> A total of 113 patients had a new implant inserted for a second

> year of therapy following removal of the first implant. Of this

> group, 68 patients had measurement of serum testosterone on Day

> 2 or Day 3 and on Day 7 after insertion of the second implant

> in order to assess for the " acute-on-chronic " phenomenon. No

> acute increase in serum testosterone was seen in any patient in

> this group following insertion of the new implant.

....

> I hope this helps.

I think it does.

If I read this correctly, not one of the patients who were tested

after receiving their second implant at the end of the first year

had a testosterone flare on the occasion of the second implant.

It therefore seems clear that the original article's claim that

cutting down on the total number of implants cuts down on the

amount of testosterone flare is just dead wrong. A second

implant, or a second Lupron or other injection, if given at the

right time, will not cause a flare. Period. Not even in a

single one of the 68 patients.

Either the doctor who explained this to the journalist was lying,

or else (at least as likely I should think) the journalist

misunderstood what he said.

Alan

[Guest guest]

>

>

>

> Metcalf <bryan.metcalf@...

> <mailto:bryan.metcalf%40virgin.net>> wrote:

>

> > I understand that Casodex molecules fit to Testosterone

> > molecules like jigsaw pieces - thus blocking the Testosterone's

> > action

>

> More precisely, from the Wikipedia article on bicalutamide

> (the generic name for Casodex):

>

> " Bicalutamide acts as a pure anti-androgen by binding to the

> androgen receptor (AR) and preventing the activation of the

> AR and subsequent upregulation of androgen responsive genes

> by androgenic hormones.[7][8] In addition, bicalutamide

> accelerates the degradation of the androgen receptor.[9] "

(snip)

A good summary.

For the rest, I recommend www.rxlist.com and searching on Casodex

or the generic, bicalutamide, or whatever is the drug of interest.

Detailed and reliable info on just about any med one can think of

is available there.

Regards,

Steve J

[Guest guest]

In response to Alan,Regarding "acute on chronic". It seems the phenomenon is not that rare (check ref 26 below for example). Because of the nature of LHRH - super agonist action it is logical to expect acute on chronic (testosterone escape) to occur with smaller LHRH-sa doses rather than larger (longer acting) doses. Surely? > A second implant, or a second Lupron or other injection, if given at the right time, will not cause a flare. Period. ly I do not see how your confidence is justified. Do you consider the small number of men tested (68) sufficient to reach a meaningful conclusion ? I don't. Clearance of these drugs is by no means well understood or easily predicted. Particularly so in younger or more energetic men with a more efficient metabolism. I know that from personal experience and it has meant me having to monitor LH/FSH and T consistently when on this kind of treatment. . Just another facet of surviving 15+ years with horrible numbers, both to start with and going on with. The take home message once again is "Do your homework properly".Sam. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2725306/?tool=pubmedLHRH agonists are associated with acute-on-chronic effect in 4% to 10% of patients treated with standard LHRH therapy.15,25 Up to 23% of men on goserelin escaped from the castrate level and overall breakthroughs are reported in the literature in 2% to 13% of patients on

LHRH agonists overall.26–28

About 2% to 17% of patients fail to achieve a serum testosterone level lower than 50 ng/dL and about 13% to 38% of patients fail to achieve a serum testosterone level lower than 20 ng/dL, as reviewed by Tombal and Berges29 and based on reports of leuprolide acetate depot formulations and goserelin implants.> > ...> > A total of 113 patients had a new implant inserted for a second> > year of therapy following removal of the first implant. Of this> > group, 68 patients had measurement of serum testosterone on Day> > 2 or Day 3 and on Day 7 after insertion of the second implant> > in order to assess for the "acute-on-chronic" phenomenon. No> > acute increase in serum testosterone was seen in any patient in> > this group following insertion of the new implant.> ...> > > I hope this helps.> > I think it does.> > If I read this correctly, not one of the patients who were tested> after receiving their second implant at the end of the first year> had a testosterone flare on the occasion of the second implant.> > It therefore seems clear that the original article's claim that> cutting down on the total number of implants cuts down on the> amount of testosterone flare is just dead wrong. A second> implant, or a second Lupron or other injection, if given at the> right time, will not cause a flare. Period. Not even in a> single one of the 68 patients.> > Either the doctor who explained this to the journalist was lying,> or else (at least as likely I should think) the journalist> misunderstood what he said.> > Alan>

[Guest guest]

sammy_bates wrote:

> In response to Alan,

>

> Regarding " acute on chronic " . It seems the phenomenon is not

> that rare (check ref 26 below for example). Because of the

> nature of LHRH - super agonist action it is logical to expect

> acute on chronic (testosterone escape) to occur with smaller

> LHRH-sa doses rather than larger (longer acting) doses.

> Surely?

That could be, I'm not qualified to say. However if I understood

the original article, the implant didn't contain a larger dose at

any one time but rather a timed release dose.

> > A second implant, or a second Lupron or other injection, if

> > given at the right time, will not cause a flare. Period.

>

> ly I do not see how your confidence is justified. Do you

> consider the small number of men tested (68) sufficient to

> reach a meaningful conclusion ? I don't.

Well, you're right, my confidence is not justified. I'm not an

expert and I shouldn't have said " Period " .

On the other hand 68 patients does strike me as a sufficiently

large sample given that 0 patients had a testosterone flare. If

you perform 10 tests and get 3 of this and 7 of that, then do it

again and get 5 and 5, again 9 and 1, etc., the data is

ambiguous and you need a large sample. But if you get 0 and 10,

then 0 and 10 again, then 0 and 10 again, 6.8 times, that's

looking pretty significant to me. It's been many years since I

studied statistics and there are others in this group who could

help us out here, but I believe that the confidence we can have

in a correlation depends on the strength of the correlation as

well as the sample size. With such an incredibly high

correlation, 1.0 in this case on a scale of 0.0 to 1.0, the

sample can be smaller than if the correlation is lower.

So I retract my " Period " and will substitute a " Most likely "

> Clearance of these drugs is by no means well understood or

> easily predicted. Particularly so in younger or more energetic

> men with a more efficient metabolism. I know that from personal

> experience and it has meant me having to monitor LH/FSH and T

> consistently when on this kind of treatment. .

What was your experience with intermittent HT? Can you tell us

how long your on and off periods were, how low your PSA got, how

high and fast it rose on the off periods, and what your

testosterone levels were?

Are you still doing well with it?

I know that you may not have data on all this unless your doctor

was very aggressive in testing you, but if you've got any useful

data, I'd love to hear it.

I know some guys do extremely well on intermittent HT and some

don't. But the ones who do well certainly appear to suffer less.

> Just another facet of surviving 15+ years with horrible

> numbers, both to start with and going on with. The take home

> message once again is " Do your homework properly " .

>

> Sam.

Alan

[Guest guest]

sammy_bates wrote:

http://en.wikipedia.org/wiki/Sample_size

> Basically it is saying that a sample size of 100 will give you

> a 10% error. That means with a sample of less that 100, even

> " given that 0 patients had a testosterone flare " the

> significance would be quite meaningless. I don't know why such

> small studies get past peer review.

I don't think it's actually saying that. I seem to recall from

my far away statistics courses that sample size for a given level

of significance is not the same for every correlation in every

population. But the math in that article is way over my head and

I can't say what the level of confidence should be when 0 of 68

samples turn out to show or not show a particular tested

characteristic.

I also seem to recall that at least one of our members here is a

math professor. Perhaps he can give us a layman's interpretation

of the issue.

Alan

[Guest guest]

It would be interesting to learn what a mathematician has to say about it.

>

> http://en.wikipedia.org/wiki/Sample_size

>

> > Basically it is saying that a sample size of 100 will give you

> > a 10% error. That means with a sample of less that 100, even

> > " given that 0 patients had a testosterone flare " the

> > significance would be quite meaningless. I don't know why such

> > small studies get past peer review.

>

> I don't think it's actually saying that. I seem to recall from

> my far away statistics courses that sample size for a given level

> of significance is not the same for every correlation in every

> population. But the math in that article is way over my head and

> I can't say what the level of confidence should be when 0 of 68

> samples turn out to show or not show a particular tested

> characteristic.

>

> I also seem to recall that at least one of our members here is a

> math professor. Perhaps he can give us a layman's interpretation

> of the issue.

>

> Alan

>