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Posted 5/10/2017 11:56 PM (GMT 0)
Thanks George...I didn't notice that.

Lowroad---email me sometime...would like to compare notes...
Posted 5/10/2017 11:58 PM (GMT 0)
A GnRH agonist or antagonist (like Lupron or Firmagon) is usually more effective than Casodex alone, especially for someone who is castration resistant. But perhaps it matters less when a man is still hormone sensitive. There's a clinical trial of Xtandi monotherapy for such a use.

I'll reprint here Traveler58's post from September. I was skeptical at first, but there is no doubt that this is controlling his cancer for the present, and the SEs seem to be very manageable. Reactions to hormone therapy are very different in different men, and there is no guarantee that what worked for him will work for you. I think it is a great discussion to have with an MO.

Traveler58 said...
I have been on Casodex mono therapy for the last two years. In 2014, when my PSA started to rise, my MO started with 150mg daily Casodex and PSA dropped from 0.8 to 0.02 in a month. Then my MO decreased the dosage to 50 mg/day. Due to breast swelling and tenderness I started Tamoxifen in May 2015 (20 mg daily in the first month, then 10 mg). After starting Tamoxifen, my testosterone decreased continuously, from 566 to 125 in 6 months. We don't know if this testosterone decrease is related with Tamoxifen usage or not. My MO wanted to see how PSA and testosterone will react with no medication, so I stopped taking Casodex and Tamoxifen for about 4 months. Testosterone level recovered but PSA started to rise as expected. So we started Casodex again, with a new dosage, one 50 mg tab per week. It was not enough, so Casodex dosage was increased to two 50 mg tabs a week. Because of the breast swelling and tenderness, I started Tamoxifen 10 mg as well. So we'll see if testosterone will start to decrease again or not and wher PSA will stabilise. Anyway, my PSA is at 0.25 and testosterone over 500 after 9 months of intermittent Casodex mono therapy. I added up all the Casodex tablets that I've taken during this 9 month period and it's only 24 tablets (50mg tabs). So it seems for me, there is good response to Casodex therapy. And the only side effect is breast tenderness and swelling and it can be fixed with a daily 10 mg Tamoxifen tablet.
Age 62 (56 when dx), surgery Jan 11, path report: t3b, GS 8 with tertiary 5, SVI, neg.margins.
PSA 3 months post op 0.03. Started Adj ADT May 11 and IMRT Jan 12. Last Lupron shot June 12.
PSA 0.003 May 11 - April 13
PSA 0.8 Nov 14
Casodex monotherapy since Dec 2014 with 50 mg daily, reduced dosage to 50 mg weekly since April 16. PSA 0.2
Urinary control, sexual function ok

Posted 5/11/2017 1:57 AM (GMT 0)

Tall Allen said...
Bob-

You may have noticed a post recently by a patient of Howard Scher's (certainly one of the best MOs anywhere), where he was taking only 1 or 2 50mg Casodex a week. This was enough to bring his PSA down to undetectable levels, yet keeps his serum testosterone high enough that he feels good - a win-win. He also takes tamoxifen to prevent breast enlargement.

There are lots of ways to do ADT and I hope you have a good MO who is willing to discuss all those options with you.

I've been following all comments in this thread with great interest and thank all for your thoughts. Like some others here I'm on the brink of needing to decide when and in what form to agree to ADT, though I am also hoping to hold out for a while in hopes that the prostvac trial at NIH shows promise and opens up for a next round. But should that long-shot not come my way I need to make decisions about ADT: should I start early or later (I've read TOAD, but am not yet convinced about early rather than later) and is Casodex monotherapy an option. Allen's comment I quoted above and a presentation by Dr. Mohler of Roswell Park that was linked above by George both suggest that Casodex monotherapy may not be a bad way to go, even though it is uncommon in the U.S. I'm questioning whether Lupron or similar agonists are really sufficiently better than anti-androgens like Casodex to make them worth the trade-off in QOL.

The particulars of my dilemma comes down to a choice between two doctors. The RO I've been with for 7 years is an outlier in the U.S. in that he favors Codex monotherapy after failed SRT rather than -- or at least as a way of postponing -- Lupron. He did his best to restrain a grimace when I told him I've now also seen an MO at Dana Farber. His opinion is that barring participating in some new and interesting trial, they will steer me toward standard Lupron or equivalent. He - the RO -- on the other hand tells me he has really good results with Casodex 50mg with less onerous side effects than Lupron and some patients have done well on it for 3 or so years and in at least one case 8 years. That sounds good to me. My main reservation is that he is a practicing RO, whereas my MO is -- well an MO -- and is also at a leading cancer center.

My RO's opinion and Dr. Mohler's comments (if I understood them correctly) in his presentation to the effect that anti-androgens like Casodex have essentially the same results as agonists such as Lupron. Though in his presentation he wasn't recommending one over the other, only saying they had similar results. I am again questioning why I would consider Lupron rather than first Casodex monotherapy. I will discuss this with my MO, and am for now also maintaining ties with my RO to keep options open. Any thoughts about this would be welcome.
Jim
Posted 5/11/2017 2:21 AM (GMT 0)
Since I'm heading for ADT by year's end, Casodex monotherapy interests me as well. I will talk to my MO about it. Questions come to mind. Are the SEs significantly less, and why? If PSA starts to rise while on monotherapy will the addition of Lurpron bring it down again? Time to do some research.
Posted 5/11/2017 2:35 AM (GMT 0)
TA said ": Lupron is more effective than Casodex alone, especially for someone who is castration resistant."
TA .. I thought you would say Lupron was more effective than Casodex as a monotherapy, but I thought once both failed you were deemed castration resistant and agonists or antiandrogens were off the table.
Posted 5/11/2017 2:53 AM (GMT 0)
My RO tells me he became curious about Casodex when sitting as an American doctor on a panel discussion 15 or so years ago with some European and (I think he said) Australian doctors. Inquiring minds might ask why is this more commonly used elsewhere than in U.S. Is it really less effective? Maybe it is -- I'd like to know. Is it perhaps less profitable, less promoted, and hence less familiar to first-line practitioners? Maybe it really is significantly less effective than Lupron-type drugs. I'd like to know. But there is no question that it is way cheaper. I was on it for three months during my SRT - my co-pay for a 90 day supply of the generic (bicalutamide) was $8 on my medical plan.

My short term side-effects were minimal, but I was on it for only 90 days at 50mg daily. By month three I was beginning to have some breast tenderness, though I understand this can be countered with tamoxifin. I noticed no other side effects in the short time I was on it -- no hot flashes, fatigue, etc.

I'd like to know how it compares to Lupron's known added cardiac, diabetic, and bone fracture risks if on it long-term; if time to failure is sooner; if Lupron might still be effective for a while after failure of Casodex?

Jim
Posted 5/11/2017 3:16 AM (GMT 0)
Bohemond..it is fair to say that since you were first diagnosed in 2002 your prostate cancer has been well managed.
You are now experiencing some faster PSA doubling times but the overall PSA is not alarming for mets.
You may be well served to try Casodex monotherapy and see its impact. With your history it is doubtful any one would say that not doing Lupron for 6 to 12 months to test the efficacy of Casodex monotherapy will have any significant impact on your treatment.
Posted 5/11/2017 4:04 AM (GMT 0)
Side effects are very individual - you won't know until you try. The big side effects associated with Casodex are breast pain and gynecomastia (breast enlargement). Tamoxifen (10 mg) prevents it very well (they used to use chest radiation, but it didn't work nearly as well). Traveller58 found that tamoxifen decreased his testosterone levels. That may be individual to him as it is not a known SE of tamoxifen, but then, most men taking it are not trying to maintain testosterone levels - so who really knows? Some have suggested raloxifene for this purpose because it may have some PC-suppressive qualities as well.

As for other side effects, it seems to have less effect on body composition (bone mineral density and fat accumulation) and hot flashes are somewhat less
ascopubs.org/doi/full/10.1200/jco.2004.01.174
/www.ncbi.nlm.nih.gov/pubmed/25523493

Since most men starting on permanent ADT with a low metastatic burden are probably going to try intermittent ADT anyway, starting off with a light dose of Casodex may be worth a try. If it isn't effective, you can always increase the dose or add Lupron. Although it isn't as effective as Lupron across the population, some men may do as well with it.
Posted 5/11/2017 11:47 AM (GMT 0)
Wow, I am definitely going to ask for Casodex alone as an experiment as it sounds way more tolerable.

How about a quick shot of firmagon to lower PSA then wean into Casodex to see if control is maintained?

Bohemond, I tried to get into the ProstVac trial and didn't qualify as my doubling time was too fast at 3 months. In reading the trial's details, half of the participants are delayed treatment for 6 months which was troubling for me. Also, a doc told me that so far response rate has been around 30%. Not great odds with a quick doubling time on your back. My main oncologist is part of a ProstVac trial though and does have a patient that has suppressed PSA for years on it. I don't the know the guy's parameters though.

I was told by the trial's contact person, Anna Couvillon, for patients that have a lesion which shows up on standard scans there is another trial using ProstVac, ADT and Taxotere. Perhaps there is some synergy there. I would consider that if I qualified.

Staying tuned said: You just don't see cases where someone says "I was a Gleason 7 , had a prostatectomy , had positive margins and SV invasion, got RT and have not had any biochemical recurrence for 10 years." (I don't know how to highlight a quote, sorry)

That hit me like a brick as that's basically me (minus prostatectomy). I have been wondering just that, if there are EVER individuals with my history that emerge from salvage therapy basically cured. Not so, huh?

Turdz....
Posted 5/11/2017 1:15 PM (GMT 0)

Yarbo3 said...
...

Staying tuned said: You just don't see cases where someone says "I was a Gleason 7 , had a prostatectomy , had positive margins and SV invasion, got RT and have not had any biochemical recurrence for 10 years." (I don't know how to highlight a quote, sorry)

That hit me like a brick as that's basically me (minus prostatectomy). I have been wondering just that, if there are EVER individuals with my history that emerge from salvage therapy basically cured. Not so, huh?

Turdz....

Actually, I think most of that is selection bias. Those guys are out on the golf course, not posting on forums like this one! This forum is not a random selection at all. We're here either because we need support, or may choose to provide support. Rarely there is a social interaction, sometimes, fun when they happen. But mostly, look at the posts. They're usually seeking answers to questions, lots of helpful responses, then some back and forth. Often, there's only one thread from someone. They get their answers and move on.

So you will only very rarely see the guy who would make a statement like that. There's what, maybe a couple of hundred posters in a year on this forum? In just the US, nearly 200,000+ diagnosed annually, almost 30,000 passing from this disease. So the interactions here are a vanishingly small piece of that population.
Posted 5/11/2017 2:41 PM (GMT 0)
Guys

Actually when I heard that I only had one 9 mm lesion on my femur I thought it was relatively good news given my rapid doubling time and poor prognosis at pathology post RP. It was also good to hear that I had no recurrence in any other area particularly pelvic lymph nodes which had a massive dose of IMRT.
When my RO offered IMRT to the new met he said it was better for me than SBRT given I had a long life expectancy because SBRT has not been proven to be effective for the long term. Now that was an encouraging statement! But has SBRT been proven to be less effective than IMRT over a long period? Has anyone seen comparison studies? Also is cyberknife essentially the same as SBRT and equally as effective?

Regarding ADT resumption, I took my first casodex pill yesterday and have a 3 month Lupron shot scheduled for next Thursday. I'll look into firmagon instead if it works more quickly. My RO is a big proponent of Snuffy Meyers who believes in throwing everything at PCa which is why I'm on all the other stuff listed in my signature.
Bob
Posted 5/11/2017 5:03 PM (GMT 0)

Yarbo3 said...
How about a quick shot of firmagon to lower PSA then wean into Casodex to see if control is maintained?

No - they do very different things. Firmagon stops testosterone production. Once you stop it, T comes back up. If you then start Casodex to block the androgen receptor, what have you gained by previously stopping T production? Why would you not just do one or the other? If Casodex doesn't work for you, it won't matter that you had a Firmagon shot in the past. If Casodex does work for you, it won't matter that you had a Firmagon shot in the past. So, the Firmagon shot is irrelevant.

Sometimes Casodex is given before Lupron to prevent testosterone flare in men who may have numerous painful metastases, but that is a different matter entirely. There is no testosterone flare with Firmagon.

Yarbo3 said...
That hit me like a brick as that's basically me (minus prostatectomy). I have been wondering just that, if there are EVER individuals with my history that emerge from salvage therapy basically cured. Not so, huh?

Are you asking whether guys who are diagnosed with SVI after prostatectomy are ever cured by salvage radiation? The answer is yes, something around 35% if I remember correctly. You are, of course, in a very different situation.
Posted 5/11/2017 5:17 PM (GMT 0)

Bob said...
But has SBRT been proven to be less effective than IMRT over a long period? Has anyone seen comparison studies? Also is cyberknife essentially the same as SBRT and equally as effective?

SBRT has been used on bone mets for many years, and is endorsed for that purpose by ASTRO, NCCN and the AUA. This RO you spoke with is obviously not an expert in this - only go to experts for such info.

CyberKnife is one brand of SBRT. It can be done with any of a number of platforms.

Bob said...
I'll look into firmagon instead if it works more quickly.

Firmagon is a substitute for Casodex+Lupron. You took the Casodex to block the androgen receptors so that when you get a Lupron shot, the testosterone surge won't activate them. Some guys start with Firmagon (instead of Casodex) and transition to Lupron later. Some guys start with Firmagon and stick with it. PDA transitioned from 3-month Lupron shots to one month Firmagon shots when he was ending his adjuvant ADT - but that is a different situation.
Posted 5/11/2017 5:46 PM (GMT 0)
Has it ever been demonstrated that Firmagone is more effective in controlling advanced prostate cancer than Lupron / Eligard ?
Posted 5/11/2017 6:20 PM (GMT 0)

Allen said...
As for the radiation, it isn't hard to find an RO who can zap it in 3-5 treatments of SBRT. The last thing you want is a fractured femur down the road, and this can help prevent it. I agree with you that IMRT for this type of thing is a relic of the past, and all professional associations warn against it.


I knew you can use SBRT for bone mets, but why is SBRT that much better for radiating bone mets than IMRT?

George
Posted 5/11/2017 6:26 PM (GMT 0)
Fairwind -

Yes:

/www.ncbi.nlm.nih.gov/pmc/articles/PMC4772358/

www.jurology.com/article/S0022-5347(11)03864-X/fulltext
Posted 5/11/2017 6:28 PM (GMT 0)
Fairwind,

the manufacturer publishes trials that found that the risk of cardiovascular events is lower than with Lupron.

George
Posted 5/11/2017 6:53 PM (GMT 0)
George_

Because it is less of an ordeal for the patient, less toxic, and it is a LOT less expensive. Of course, many IMRT ROs object to any kind of hypofractionation because it cuts into their profits. In the US, ROs are reimbursed by insurance by the number of treatments.

The other benefit to SBRT is that it can be repeated if local control is incomplete. The dose received by healthy nearby tissues is much less with SBRT than with IMRT.

www.ascopost.com/News/48372

In addition to those treatment schedules, some ROs give 3 x 10 Gy or 5 x 5 Gy. They all seem to work equally well.
Posted 5/11/2017 7:12 PM (GMT 0)
Thank you Allen, I agree with the reasons you mentioned. 3 x 10 Gy or 5 x 5 Gy are typical doses for SBRT, sometimes the SBRT ROs give just one fraction about 20 Gy instead.
/www.cyber-knife.net/fileadmin/user_upload/pdf/CK_PC.pdf

The article you mentioned seems to refer to IMRT though and mentions that SBRT should only be used in clinical trials. This is confusing to me.

George

Post Edited (George_) : 5/11/2017 1:20:03 PM (GMT-6)

Posted 5/11/2017 7:51 PM (GMT 0)
IMRT usually refers to fraction sizes of 2 Gy or less; SBRT to fractions of 5 Gy or more; fractions >2 and <5 are usually called "hypofractionated IMRT."

Technically, SBRT is intensity modulated (i.e., IMRT) and highly conformal (like 3D-CRT) and image guided (ie IGRT). It is all that and more. But in normal parlance, people use the term SBRT (or sometimes SABR) to refer to extreme hypofractionation.
Posted 5/11/2017 8:31 PM (GMT 0)
Two month PSA number post SBRT to one hot lymph node is in at 1.4 at Quest Labs. The same lab measured PSA at 3.5 prior to treatment. To me, this is good news. Cancer cells of all stripes are getting killed, not just hormone sensitive ones. My cancer burden is being reduced, will that translate to longer life? I don't know, but to me it is worth a try.
Woody
Posted 5/11/2017 9:17 PM (GMT 0)
TA
I believe that the ROs who push IMRT feel that SBRT has not undergone a phase 3 clinical trial to prove its long term effectiveness. Therefore it's not the standard of care for RT to the prostate.
Why is SBRT preferred for bone mets ? Is it because a lower dose is necessary in terms of grays?
Bob
Posted 5/11/2017 9:48 PM (GMT 0)

Bob said...
I believe that the ROs who push IMRT feel that SBRT has not undergone a phase 3 clinical trial to prove its long term effectiveness. Therefore it's not the standard of care for RT to the prostate.

Are you talking about SBRT to mets or SBRT to prostate? For mets - see the link to the ASCOpost that I just posted. For prostate - there has been a phase 3 trial of SBRT vs IMRT in Scandanavia - so far the toxicity outcomes have been released and they look good. There has never been a Phase 3 trial of dose-escalated IMRT compared to dose escalated 3D-CRT. In fact, the length of follow-up on both IMRT and SBRT are about the same. It certainly is a standard of care, if you think that ASTRO defines standard of care.


Bob said...
Why is SBRT preferred for bone mets ? Is it because a lower dose is necessary in terms of grays?

Read the reply I just gave to George who asked the same question.
Posted 5/12/2017 8:08 PM (GMT 0)
TA
The ascopost link you posted if I understand it correctly seems to recommend SBRT to alleviate pain from mets. It doesn't seem to address SBRT to asymptomatic mets like mine. Am I putting to fine a point on when it's appropriate?
Now that I've decided to go back on ADT3, how long if at all should I wait to zap the new met?
Bob
Posted 5/12/2017 8:54 PM (GMT 0)
It has been observed that Tamoxifen can reduce the PSA value. In this little study which wanted to determine the potential role of prolactin as a tumor growth factor for prostate cancer they report:

"A decline greater than 50% in prostate-specific antigen (PSA) levels occurred in 4/14 (29%) patients within the first 2 months of therapy, with a median duration of 5 months."
A phase II study of tamoxifen in hormone-resistant metastatic prostate cancer: possible relation with prolactin secretion.

This group where the decline in the PSA value was observed had higher prolactin values than the rest of the patients in the study.

So it is likely that the combination of Casodex and Tamoxifen was required to achieve the decline in PSA value reported by Traveller58.

George
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