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Old 09-23-2011, 04:13 PM   #1
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Smile Going from incurable to likely curable!!!

Two days ago I passed a major milestone: moving from the incurable state to "likely curable"!

I fully realize I am far from cured at this point and that I still have a PSA that moves up rather quickly in the latter months of the off-therapy vacation period from modern hormonal therapy, but after a thorough exam and review of tests, an expert believes I have an 80% chance for a cure! Pretty amazing for a guy who started out in December 1999 with a PSA over 100, with a biopsy of GS 4+3=7, with all cores positive, most 100%, with androgen deprivation therapy (ADT) as my sole therapy, and with a prognosis from each of two respected doctos that I likely had five years to live, with two of them in decline! This possibility of cure in the near future was unexpected. I had of course been hoping for this as a possibility some time in the future, but it took me by surprise.

I have great respect and appreciation for my local doctor, a talented and dedicated general medical hematologist/oncologist, but I'm nearing the point where I'll be starting the fourth cycle of ADT3, and the PSA pattern at the end of my last ADT3 cycle showed possible evidence of an androgen receptor mutation where the cancer has transformed itself so it can use one of the drugs - bicalutamide (Casodex) - as fuel. I decided this was the time to get the opinion of one of the leading experts in prostate cancer and ADT, Dr. Charles Myers, MD, whom many of us know by his nickname, "Snuffy".

I saw him two days ago. The most surprising thing was the result of the DRE: my prostate was virtually normal, with just one possibly questionable area! That's amazing to me in view of the fact that I have been off the heavy-duty drugs, Lupron and Casodex, since their influence mostly ran out in April 2010, about seventeen months ago. Dr. Myers also considered a recent battery of tests (PSA, DHT, 25-hydroxy vitamin D, testosterone, lipds, etc.), a thorough physical exam at his clinic, as well as all records for the past year, all scans, doctors' reports, and results from the period around my diagnosis. I had also provided a detailed chronology of all test results since diagnosis. He viewed all of this from his perspective as an expert with a practice dedicated to prostate cancer patients in which he works with more than 1,100 patients a year. My take on his comments was that the hormonal therapy I have had has mostly eliminated cancer from my prostate, with remaining cancer probably located only in a limited number of lymph nodes, where it can be precisely located with modern imaging and targeted with expertly delivered radiation! This is pretty amazing stuff! By amazing stuff, I mean it's awesome that hormonal therapy has eliminated so much of the cancer (it's known to be able to eliminate lower Gleason score cancer) and also that there have been nearly unbelievable advances both in imaging and in targeting revealed cancer with radiation.

Dr. Myers has worked with about 250 men who have had advanced lymph node imaging, first with Combidex, done in the Netherlands, and more recently with the feraheme Ultra Small Superparamagnetic Iron Oxide (USPIO) contrast high-resolution (3 Tesla magnetic field) MRI imaging done by Sand Lake Imaging in Orlando, Florida. The former is no longer available, but the latter is about to emerge from investigational status when Dr. Bravo at Sand Lake publishes his paper about results. The paper is expected to show that a cancer in any lymph node as large as just 2 mm, sometimes even down to 1 mm, will be reliably picked up by the scan and precisely located. At the Conference on Prostate Cancer earlier this month, Dr. Myers told the audience some exciting news: about 70% to 80% of his patients who were suitable for feraheme USPIO imaging turned out to have cancer in lymph nodes that could be targeted by radiation - sometimes the only cancer in the body that could be detected, and about half of them experienced PSA declines to ZERO after treatment! Many of these men had experienced recurrences that were too aggressive for surveillance and tactics involving lifestyle measures and mild medications. Some, like a friend of mine who has gone through this, had been battling aggressive recurrences for many years. They were a challenging group, making such success all the more impressive. I'll be posting more about this in reviewing the conference.

While Sand Lake Imaging is the sole site where feraheme USPIO imaging for prostate cancer is now available, Dr. Bravo and the doctors referring patients to him expect that this technology will spread rapidly and widely once his paper is published. That's because any cancer imaging facility with equipment that can muster a 3 Tesla magnetic field will be able to do the scan; all it will need is the feraheme contrast agent, and that agent has already been approved by the FDA for other imaging purposes. Obviously, this development will have a huge impact on the treatment of prostate cancer, especially advanced prostate cancer and challenging cases. It might also come to play a large role in decisions whether a patient who needs some kind of treatment (other than active surveillance) should rely on a local therapy (such as surgery or radiation) or use a more aggressive approach. By the way, for many of those now having the scan, the cost of the scan is covered by insurance except for the contrast agent, which costs nearly $1,000. That too may be covered if the FDA approves the scan for prostate cancer. I'm thinking the Bravo, Dattoli, Myers study may lay the groundwork for such approval.

I wanted to share this good news of mine before getting into the recent prostate cancer conference and also into concerns that have been raised on the Board. As for my own current situation, that last PSA test showed a continuing decline to 8.8 under the influence of low-dose thalidomide (with 300 mg of vitamin B6 to help prevent peripheral neuropathy) - an investigational approach that has worked well twice before for me. Here's how my PSAs have gone in the latter months of my third vacation period from the heavy-duty drugs, with a few results from the months around the time I went "off therapy":

12/24/2009 0.04
3/2/2010 0.03 (and steadily declining to this point)
4/2/2010 0.04 (Whoops - not so happy about that! My doctor and I
decided I might as well go off therapy at this point as my PSA was unlikely
to drop further. I had been aiming for a result of <0.01, which I had
achieved on the two previous IADT3 cycles.
6/15/2010 0.02 (That was a surprise as the heavy duty drugs - Lupron and
bicalutamide, had run their course by around mid-April. I was glad for the
decline, but it did open the possibility that the cancer had begun to use
the bicalutamide as fuel. I can explain if anyone is interested.
Fast forward to
6/22/2011 9.76
7/7/2011 Started low-dose thalidomide with 300 mg of vitamin B6 daily.
7/26/2011 10.97 While this result was substantially higher, the rate of PSA
increase had fallen sharply. This indicated the thalidomide approach was
working once again.
8/8/2011 9.48 I was glad to see this clear confirmation of success.
9/3/2011 8.8

I'm hoping the thalidomide will work for a total of six to seven months, as it had in the past two cycles, or longer. When my PSA begins to rise again for at least a month, that's likely the time I'll go for a feraheme USPIO scan. I would also have an advanced, more sensitive bone scan known as F18 to rule out spread to bones, which now looks quite unlikely in my circumstances.

Enough about me. I'm a walking example of what is possible when we succeed in buying time for technology to advance to the point that new ways of effective treatment open up. I realize there are no guarantees, but I am elated to be where I am now!

Jim

Last edited by IADT3since2000; 09-23-2011 at 04:26 PM. Reason: Added point about the F18 bone scan shortly after posting.

 
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Old 09-23-2011, 04:40 PM   #2
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Re: Going from incurable to likely curable!!!

Hello!

Two days ago I passed a major milestone: moving from the incurable state to "likely curable"!

We have not met before, but I happened upon your thread and just had to stop and celebrate with you! What joyful, joyful news. It looks like treatment and technology have come together for you. What a blessing.
I am yelling a "hallelujah" out loud for you as I type. :-)

Thank you for sharing your news. My heart was racing after I read the first sentence of your post and a big smile found its way to my face. I know others will find pleasure in you post as well.

God Bless you and keep you
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Old 09-23-2011, 11:00 PM   #3
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Re: Going from incurable to likely curable!!!


There's a party going on inside of me right now...I'd scream with joy if it weren't so late at night...I'm so excited for you!!!!

It's interesting too because I keep thinking about Sandlake Imaging in Irv's future, and the possibility of very focused radiation. You see, a small change had been noticed on a lymph node on his iliac crest on his second CT scan which was done after surgery. There was differing opinions from the various doctors discussing his case about whether the change was due to the cancer or possibly to something totally unrelated, like scarring from his colitis. Since his colitis has been in remission for years, I believe strongly that it isn't that. My feeling has always been that I agreed with the doctor who believed that it could be cancer on that node that accounted for the remaining PSA after surgery.

However, at present, I figured that Irv has been through enough and, as long as the hormone therapy is working, we'll hang tight on any further treatment. Furthermore, I've also read about ARM and, if Irv's PSA ever starts to rise, I've read about one guy who eliminated bicalutamide and the PSA dropped again, and then, after it started rising, he reintroduced bicalutamide and the PSA started to drop again. Also, there are some who switch to, I believe it's called Flutamide and sometimes just switching the medication did the trick. In future, I know that we can always revisit the idea of more sophisticated imaging and safer radiation (proton beam??) which will, hopefully, be less of a risk to Irv's colitis.

I'm so glad, Jim, that you're finding such success with your disease. You are a shining light of hope for all of us here.

One last thing....Irv's most recent PSA level was .03 and he's due to have another one at the end of the month. I'm hoping for .02 or better...or at very least, no change. His next injection is due in November and we'll check his PSA again. Based on those numbers, we have to make a decision. These are my thoughts and opinions are always welcome: If the PSA keeps going down, and we continue to see a drop, then I'd recommend another injection to see if the drop continues. The goal is to push it down as low as possible since we don't know the nadir yet. If, on the other hand, the PSA remains the same over the next two checks, I'm guessing then that we've reached the nadir and, perhaps it's time for a vacation at that point. If we notice a rise (hopefully this won't happen), then stop the bicalutamide to see if that pushes the PSA back down and go for another injection.

The long and the short of it is that I'm wondering, Jim, if you've heard any of the latest thoughts, at the conference, on how long one should stay on the ADT before a vacation period. I used to think that Irv should have two more injections for a total of 15 months on the heavy drugs but, now, my thoughts are that one more injection, for a total of one year might be the better alternative. What are your thoughts on this?

Thanks again for the good news. I haven't felt this happy and hopeful since Irv's diagnosis.

Rhonda

 
Old 09-24-2011, 01:16 AM   #4
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Re: Going from incurable to likely curable!!!

Great news, Jim! I can't begin to imagine how that will change your life, but I'm sure you've dreamed about that day. And how amazing is it that you've been able to actually reverse the course of your disease owing to your own great efforts! You are a model for all of us, and I hope many will emulate your approach.

At the PCRI Conference, I was very impressed by Dr. Myers' definition of "oligo-metastatic disease." For those who weren't at the conference, he has found that PC often progresses first to a few lymph nodes, often those near the iliac artery, where it seems to hang out for awhile before traveling systemically. He has found that 50% of recurrences are nested in a few (oligo-) spots. With good visualization aids, he can stop the cancer completely as long as it hasn't progressed to more than 5 lesions. He uses external radiation, but mentioned the possibility of using internal radio-sources (Samarium or Alpharadin), perhaps combined with Xgeva (denosumab) which has been approved for bone mets.

The trick is imaging those lesions. The FDA has placed very stringent requirements that have hampered the commercial development of many of the best contrast agents. PET scans are the best we currently have for visualizing bone mets. Choline is rapidly metabolized by bone mets, and adding some positron-emitting carbon (C11) or fluorine (F18) to the choline molecule makes them visible to the PET machine. C11 Choline is only available at the Mayo Clinic, and F18 Choline is not yet FDA approved. There is limited sensitivity data on many of the others, but Prostascint and F18 fluorodeoxyglucose (FDG), which are widely available, are not very sensitive. C11 Acetate is FDA approved, has a somewhat better sensitivity, but only a 20 minute half-life, so the facility has to have a cyclotron in the same building. Medicare recently approved NaF18 pet scans, which outperforms traditional bone scans.

Feraheme (and Combidex, which as Jim said, is no longer available after the FDA turned it down) are unique in detecting lymph nodes -- they turn black on an MRI due to iron uptake, unless the lymph node is cancerous. Coincidentally, feraheme is also currently available as a treatment for iron-deficiency anemia due to kidney disease. It is not unreasonable that someone on ADT may show symptoms of that anemia, and insurance will then have to pay for feraheme treatment. If that person happens to get an MRI while on that medicine... (hint, hint).

Since this is Prostate Cancer Awareness Month, it is a good opportunity to write to our legislators to exert pressure on the FDA to expedite approval of these contrast agents and to eliminate burdensome regulations. I'll get off my soapbox now.

- Allen

 
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Old 09-24-2011, 06:06 AM   #5
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Re: Going from incurable to likely curable!!!

Jim

I am thrilled about your news. I really hope that the USPIO shows the hiding place of the bandit and that your case passes to “history”. It vanishes for good. You deserve it and I congratulate you for the long years in the fight.
This is not the first time I read references that the hormonal treatment “cures” cancer and in your case with an initial diagnosis of voluminous aggressive form of Pca, it gives to the many of us the impetuous and hope for a similar outcome.

I am celebrating your news with my dearest red wine.

Thanks for sharing your experience.

Baptista

 
Old 09-24-2011, 12:24 PM   #6
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Re: Going from incurable to likely curable!!!

I've come back to acknowledge the self absorbed tone of some of my messages, the one above being an extremely good example. :P I do, however, want to emphasize how incredibly happy I am for you, Jim and I didn't lose sight of your moment! You've been battling this incidious disease for over a decade and the thought that you just very well could win the fight is beyond what we've all ever imagined in the case of hormone therapy. We've all been hearing (throughout the years, I'm sure) that hormone therapy is NOT a cure and doctors here have told Irv that it works on average of two years before it becomes ineffective. You, and others I've heard about, have proven that, at least one of those "facts" could very well be grossly inaccurate (if done effectively) and are well on your way to proving the inaccuracy of the other (especially if combined with sensitive scanning and well positioned radiation).

Your case is a beacon of light shedding a renewed sense of hope and positive outlook on this ******* disease. (That's why my mind was doing flip-flops over Irv last night and I was feeling happy and proud that my prior thoughts of Sand Lake Imaging and radiation in Irv's future could be dead-on). I'd like to see cases like yours show up in medical journals in the future as a pivotal point in what we know about prostate cancer cure.

Keep up the good work towards that goal, Jim!

Rhonda

 
Old 09-26-2011, 07:44 AM   #7
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Re: Going from incurable to likely curable!!!

Thanks Jim for another GREAT report, and I am really happy for your success in fighting this disease. Rich

 
Old 09-26-2011, 10:22 AM   #8
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Re: Going from incurable to likely curable!!!

Your case is surely viewed as encouragement for anyone with this disease. One can hope that in time, technology improves in order for a full cure to be developed.
Bob

 
Old 09-28-2011, 07:53 AM   #9
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Re: Going from incurable to likely curable!!!

Jim, that is such great news! I bet you are on top of the world at this point. Also what you have reported gives the rest of us who wonder what will happen in the future, some hope that there could be a cure for us in the future.

Wonderful, simply wonderful !!

Lionel

 
Old 09-28-2011, 10:58 AM   #10
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Re: Going from incurable to likely curable!!!

Hi Rhonda,

I've finally found some time to participate on the board after my initial post, and I'll be thanking all for their good wishes and thoughts, but I want to respond to your posts #3 and #7. You wrote in #7:


Quote:
I've come back to acknowledge the self absorbed tone of some of my messages, the one above being an extremely good example. :P
It strikes me that you and Irv are right where you need to be at this point. It takes great focus and energy to work for the best outcome in a system that is geared for routine outcomes instead of what is truly required. It helps when you've had some success with your case, adding credibility that can withstand the naysaying of negative doctors. You and Irv are already seeing solid signs of success.

Quote:
I do, however, want to emphasize how incredibly happy I am for you, Jim and I didn't lose sight of your moment! You've been battling this incidious disease for over a decade and the thought that you just very well could win the fight is beyond what we've all ever imagined in the case of hormone therapy.
Thank you very much!

Quote:
We've all been hearing (throughout the years, I'm sure) that hormone therapy is NOT a cure
I'm not sure what the real score is on that point. Here is what I think. I believe that hormonal therapy does not lead to a durable cure without the need for maintenance therapy for high Gleason score prostate cancer, especially GS 8-10, except possibly in rare cases. I also believe that hormonal therapy, especially triple Androgen Deprivation Therapy (ADT), can eliminate much lower grade prostate cancer, particularly cancer up through GS 3+3=6. However, whether that constitutes a cure, unaided by mainenance with finasteride or Avodart, for a patient who truly has only GS 6 or lower cancer, has not yet been proven, and there is not a lot of strongly supportive evidence. There is some interesting evidence from Dr. Robert Leibowitz's practice with fairly long-term follow-up of long-term outstanding cancer control and disappearance of side effects for low-risk patients who are maintained with finasteride. In my own case, I'm thinking that a lot of the Gleason grade 3 cancer I had has probably been eliminated.

Quote:
and doctors here have told Irv that it works on average of two years before it becomes ineffective. You, and others I've heard about, have proven that, at least one of those "facts" could very well be grossly inaccurate (if done effectively) and are well on your way to proving the inaccuracy of the other (especially if combined with sensitive scanning and well positioned radiation).
There is now so much credible evidence that the two year forecast is simply wrong and highly misleading for many patients. The imaging and well-targeted radiation are real breakthroughs!

Quote:
Your case is a beacon of light shedding a renewed sense of hope and positive outlook on this ******* disease. (That's why my mind was doing flip-flops over Irv last night and I was feeling happy and proud that my prior thoughts of Sand Lake Imaging and radiation in Irv's future could be dead-on). I'd like to see cases like yours show up in medical journals in the future as a pivotal point in what we know about prostate cancer cure.
I'm eager to see the Bravo, Dattoli, Myers paper published. Word of the feraheme technology is getting around informally, but the medical world needs formal publication to catch its attention.


You wrote in post #3:

Quote:
Originally Posted by honda50 View Post
...There's a party going on inside of me right now...I'd scream with joy if it weren't so late at night...I'm so excited for you!!!!
The day will come soon when you and Irv will be able to encourage others with a similar account. You have both already achieved a lot!

Quote:
It's interesting too because I keep thinking about Sandlake Imaging in Irv's future, and the possibility of very focused radiation.
One discouraging note at the overwhelmingly optimistic conference was that imaging in Canada was considered perhaps the most lagging among English speaking countries. If unchanged, that would mean you might have to go outside of Canada to get feraheme USPIO imaging, even after the paper is published and the technology is broadcast and implemented widely. Of course, and let's hope, Canadian imaging practices could change.

Quote:
You see, a small change had been noticed on a lymph node on his iliac crest on his second CT scan which was done after surgery. There was differing opinions from the various doctors discussing his case about whether the change was due to the cancer or possibly to something totally unrelated, like scarring from his colitis. Since his colitis has been in remission for years, I believe strongly that it isn't that. My feeling has always been that I agreed with the doctor who believed that it could be cancer on that node that accounted for the remaining PSA after surgery.
That is the kind of recurrence that the new approach is apparently curing. It appears that up to five mets is a magic range - beyond that indicates wider spread disease that is difficult to cure, at least as of today.

Quote:
However, at present, I figured that Irv has been through enough and, as long as the hormone therapy is working, we'll hang tight on any further treatment. Furthermore, I've also read about ARM and, if Irv's PSA ever starts to rise, I've read about one guy who eliminated bicalutamide and the PSA dropped again, and then, after it started rising, he reintroduced bicalutamide and the PSA started to drop again. Also, there are some who switch to, I believe it's called Flutamide and sometimes just switching the medication did the trick.
Dr. Myers confirmed my concern that I could have been experiencing the earliest stage of an ARM at the beginning of the current vacation period, and I'll be discussing a switch to flutamide with my local oncologist. I believe that's what I will be doing as the second part of my triple ADT approach. I discussed use of Nilutamide with Dr. Myers, but he prefers flutamide in this backup role and is not enthusiastic about it because of a side effect on night vision and a side effect of causing very serious pneumonia in some patients. Moreover, he said that flutamide as part of IADT3 in a backup role is effective for a lot longer period than some early research suggested. I was glad to hear that.

Quote:
In future, I know that we can always revisit the idea of more sophisticated imaging and safer radiation (proton beam??) which will, hopefully, be less of a risk to Irv's colitis.
Yes. Time is often on our side. It's quite possible that in time a different approach, such as safely revving up the immune system, will prove highly curative.

Quote:
I'm so glad, Jim, that you're finding such success with your disease. You are a shining light of hope for all of us here.

One last thing....Irv's most recent PSA level was .03 and he's due to have another one at the end of the month. I'm hoping for .02 or better...or at very least, no change. His next injection is due in November and we'll check his PSA again. Based on those numbers, we have to make a decision. These are my thoughts and opinions are always welcome: If the PSA keeps going down, and we continue to see a drop, then I'd recommend another injection to see if the drop continues. The goal is to push it down as low as possible since we don't know the nadir yet. If, on the other hand, the PSA remains the same over the next two checks, I'm guessing then that we've reached the nadir and, perhaps it's time for a vacation at that point. If we notice a rise (hopefully this won't happen), then stop the bicalutamide to see if that pushes the PSA back down and go for another injection.

Those thoughts appear sound from my viewpoint.

The long and the short of it is that I'm wondering, Jim, if you've heard any of the latest thoughts, at the conference, on how long one should stay on the ADT before a vacation period. I used to think that Irv should have two more injections for a total of 15 months on the heavy drugs but, now, my thoughts are that one more injection, for a total of one year might be the better alternative. What are your thoughts on this?

Thanks again for the good news. I haven't felt this happy and hopeful since Irv's diagnosis.

Rhonda
I was listening for opinions on the length of blockade at the conference as at least two of the experts in triple ADT were there. At some point I want to do a thorough review of the conference DVD, which is not yet available, and relate it to my notes, but at this point my impression is that the experts are thinking a duration of about a year is probably best. It is clear that they feel this is not yet a settled matter, and it is also clear that they are edging toward shorter periods on ADT3 than they have favored in the past (such as around a year and a half, provided the PSA had dropped to <0.05, with Dr. Myers favoring a drop to <0.01.) The men in Dr. Leibowitz's series of ADT3 patients almost all were on ADT3 for thirteen months, but that leaves open the question of how they would have done with a twelve month program.

Take care and keep up the great work,

Jim

Last edited by IADT3since2000; 09-28-2011 at 11:03 AM. Reason: Correcting post reference numbers.

 
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Old 09-28-2011, 11:54 PM   #11
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Re: Going from incurable to likely curable!!!

Hi Jim,

Thank you for the detailed reply. I'll respond to what you've said below:
Quote:
Originally Posted by IADT3since2000 View Post

It strikes me that you and Irv are right where you need to be at this point. It takes great focus and energy to work for the best outcome in a system that is geared for routine outcomes instead of what is truly required. It helps when you've had some success with your case, adding credibility that can withstand the naysaying of negative doctors. You and Irv are already seeing solid signs of success.

I appreciate that, Jim. However, not to seem negative, but I don't think we've seen a long enough duration yet to convince the doctors that triple blockade would make a difference to mono-therapy. After their two year mark, if Irv manages to keep going with the good results or, even better yet, manage to control the cancer in his off-periods with Avodart alone for an extended period of time, then maybe they'll start to wonder if there's something to this. I can only hope.

I'm not sure what the real score is on that point. Here is what I think. I believe that hormonal therapy does not lead to a durable cure without the need for maintenance therapy for high Gleason score prostate cancer, especially GS 8-10, except possibly in rare cases. I also believe that hormonal therapy, especially triple Androgen Deprivation Therapy (ADT), can eliminate much lower grade prostate cancer, particularly cancer up through GS 3+3=6. However, whether that constitutes a cure, unaided by mainenance with finasteride or Avodart, for a patient who truly has only GS 6 or lower cancer, has not yet been proven, and there is not a lot of strongly supportive evidence. There is some interesting evidence from Dr. Robert Leibowitz's practice with fairly long-term follow-up of long-term outstanding cancer control and disappearance of side effects for low-risk patients who are maintained with finasteride. In my own case, I'm thinking that a lot of the Gleason grade 3 cancer I had has probably been eliminated.

I'm hoping that's true. Whatever the case may be, I find it very impressive that the Thalidomide is doing such a good job of keeping you off of Lupron and Bicalutamide for such an extended period of time!

There is now so much credible evidence that the two year forecast is simply wrong and highly misleading for many patients. The imaging and well-targeted radiation are real breakthroughs!

It sure gives a lot of hope. Is it Proton beam therapy that you're referring to? I'm wondering if the radiation available now would still be a huge risk for Irv of aggravating his colitis which has been in remission for about 8 years now. It wouldn't be very nice to trade off one problem for another very unpleasant one (like the idea of a colostomy...ugh).

The day will come soon when you and Irv will be able to encourage others with a similar account. You have both already achieved a lot!

Again, thank you, Jim, for your wonderful positivism. I think I've definitely learned a lot, most of the credit goes to you, of course! However, I need to see longevity with Irv's treatment before I'm convinced that a lot has already been achieved. We're still at the baby stages of Irv's fight against this disease. I hope that makes sense and that I don't sound overly negative. I can say that, in most cases, thanks to you, I feel very hopeful for the future, but, still, sometimes I need a helping hand of support to get me back up when I'm feeling a little down over this. You and this fantastic forum have been such a great help with that right from the beginning.



One discouraging note at the overwhelmingly optimistic conference was that imaging in Canada was considered perhaps the most lagging among English speaking countries. If unchanged, that would mean you might have to go outside of Canada to get feraheme USPIO imaging, even after the paper is published and the technology is broadcast and implemented widely. Of course, and let's hope, Canadian imaging practices could change.

Well, if we have to incur the expense to go outside of Canada, we will. However, what is your opinion on this? Is this something we can hold off on? I'm guessing if Irv's vacation periods are extended, then the answer would be a resounding YES! However, if the cancer proves to be more aggressive than that, I wonder if following your route with several sessions of ADT3 before it stops working would be unwise before seeking out the scanning and possibility of radiation. Afterall, we still have to keep the colitis concern in mind. I'd appreciate your thoughts on this.

That is the kind of recurrence that the new approach is apparently curing. It appears that up to five mets is a magic range - beyond that indicates wider spread disease that is difficult to cure, at least as of today.

That would be interesting to know. Irv didn't have a "recurrence" in the usual sense. His cancer was just never eliminated for any period of time after surgery. His PSA was never undetectable. The unanswered question would be, then, how long has the cancer been outside of the prostate? He had a unifocal positive margin and extracapsular extension, as well as seminal vesicle invasion. His first PSA check after surgery was 1.12. The doctor seemed to think that would indicate a high probability of systemic cancer. I'm hoping that cancer confined only to the lymph nodes around the pelvic area could account for that remaining PSA....and, if there are only 5 areas of metastasis or fewer, where could these areas be which would still offer hope of a cure? Is it possible, if they are found elsewhere in the body besides the lymph nodes, that there is still a chance of cure with radiation to those areas? Was any of this discussed in detail and would you happen to know the answers to these questions based on the information which was addressed at the conference?


Dr. Myers confirmed my concern that I could have been experiencing the earliest stage of an ARM at the beginning of the current vacation period, and I'll be discussing a switch to flutamide with my local oncologist. I believe that's what I will be doing as the second part of my triple ADT approach. I discussed use of Nilutamide with Dr. Myers, but he prefers flutamide in this backup role and is not enthusiastic about it because of a side effect on night vision and a side effect of causing very serious pneumonia in some patients. Moreover, he said that flutamide as part of IADT3 in a backup role is effective for a lot longer period than some early research suggested. I was glad to hear that.

I'm not really clear on what you're saying here...Is it the Nilutamide which has the side effect on night vision and causing serious pneumonia? Or does the Flutamide also have those possible side effects? Also, what do you think of the idea of starting the hormone therapy again without bicalutamide and stay with it while the PSA declines and then, once you see a rise again, go back on the Bicalutamide and watch for a drop again? It worked in the case of one man who I read about. Then, if that is no longer effective, at that point switch to Flutamide. What's your thought on that?

Yes. Time is often on our side. It's quite possible that in time a different approach, such as safely revving up the immune system, will prove highly curative.

Are you referring to treatments like Provenge here? I don't like what I've read that it extends life for only about 4 months...What's 4 months for $90,000? ....I don't get that logic. What am I missing? I prefer the idea of sensitive imaging and zapping the positive areas. I wonder if safer radiation for colitis patients will be available in the future...Again, it would be interesting to know your opinion on this.

I was listening for opinions on the length of blockade at the conference as at least two of the experts in triple ADT were there. At some point I want to do a thorough review of the conference DVD, which is not yet available, and relate it to my notes, but at this point my impression is that the experts are thinking a duration of about a year is probably best. It is clear that they feel this is not yet a settled matter, and it is also clear that they are edging toward shorter periods on ADT3 than they have favored in the past (such as around a year and a half, provided the PSA had dropped to <0.05, with Dr. Myers favoring a drop to <0.01.) The men in Dr. Leibowitz's series of ADT3 patients almost all were on ADT3 for thirteen months, but that leaves open the question of how they would have done with a twelve month program.

Take care and keep up the great work,

Jim
More and more I'm thinking that it would be wise for Irv to have just one more injection to make it one year in the "on" phase before coming off the heavy duty drugs. The only situation that would make me question this is if we see an upturn in Irv's PSA before that (which I don't suspect, and hope, won't happen), in which case I think it would be good to eliminate the Bicalutamide and see what happens as a result of that. Even if it stays the same, at .03, I still think it would be good to hold it down for a few more months (one more injection) and then celebrate as he comes off and keep our fingers and toes crossed for a long "OFF" period maintained with Avodart.

(Hmmm...so many questions...I sure keep you busy, Jim! One of these days I gotta get myself to Anandale and take you out for dinner!)

Respectively, Rhonda

 
Old 09-29-2011, 03:33 PM   #12
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Re: Going from incurable to likely curable!!!

Hi Allen (and fellow Board participants),

Thank you! I'm glad you were able to come to the conference. There was so much presented and it came at us so rapidly that having at least two of us there to absorb it and compare notes here will be a great advantage. I'll respond to your post #4 of 9/24 with some thoughts in green.


Quote:
Originally Posted by Tall Allen View Post
...
At the PCRI Conference, I was very impressed by Dr. Myers' definition of "oligo-metastatic disease." For those who weren't at the conference, he has found that PC often progresses first to a few lymph nodes, often those near the iliac artery, where it seems to hang out for awhile before traveling systemically. He has found that 50% of recurrences are nested in a few (oligo-) spots.
The idea that many of us with advancing prostate cancer do not have systemic disease but rather disease in just a few lymph nodes (oligometastatic disease that you mention) is not original with Dr. Myers, but he has sure moved quickly to put that concept to work in his practice after finding it to be valid. He essentially changed his practice for such men in a fundamental way after studying a paper about oligometastatidc disease for prostate cancer a few years ago. He wrote about the source document in his newsletter, but I do not have access to it at the moment.

Quote:
...
The trick is imaging those lesions. The FDA has placed very stringent requirements that have hampered the commercial development of many of the best contrast agents. PET scans are the best we currently have for visualizing bone mets. Choline is rapidly metabolized by bone mets, and adding some positron-emitting carbon (C11) or fluorine (F18) to the choline molecule makes them visible to the PET machine. C11 Choline is only available at the Mayo Clinic, and F18 Choline is not yet FDA approved. There is limited sensitivity data on many of the others, but Prostascint and F18 fluorodeoxyglucose (FDG), which are widely available, are not very sensitive. C11 Acetate is FDA approved, has a somewhat better sensitivity, but only a 20 minute half-life, so the facility has to have a cyclotron in the same building. Medicare recently approved NaF18 pet scans, which outperforms traditional bone scans.

Feraheme (and Combidex, which as Jim said, is no longer available after the FDA turned it down) are unique in detecting lymph nodes -- they turn black on an MRI due to iron uptake, unless the lymph node is cancerous. Coincidentally, feraheme is also currently available as a treatment for iron-deficiency anemia due to kidney disease. It is not unreasonable that someone on ADT may show symptoms of that anemia, and insurance will then have to pay for feraheme treatment. If that person happens to get an MRI while on that medicine... (hint, hint).
I am so impressed with the feraheme Ultrasmall Superparamagnetic Iron Oxide (USPIO) high-resolution MRI (meaning a 3 Tesla magnetic field). It can reliably pick up cancer in nodes as small as 2 mm, and even sometimes as small as 1 mm, and, in conjunction with other imaging, can precisely locate it! In this era we have almost come to take technological breakthroughs for granted, but this one is pretty near a miracle in my book. It's the technology that may be in my future before too long - perhaps a few months. I've heard that insurance will cover all but the contrast agent itself, which runs a little under a thousand dollars. For many of us that is not prohibitive. It will be better if the FDA approves feraheme as a contrast agent for prostate cancer, but at least we now have an agent and imaging system that is practical for many patients. It takes just two days on site.

I'm thinking that the C11 acetate and the feraheme USPIO scans may be competing for the same imaging jobs. As feraheme is already approved for the other imaging work that you mention, and as feraheme does not have an issue like the cyclotron requirement, it looks to me like feraheme is the front runner here. However, it is important for Dr. Bravo to get his paper published on feraheme results for prostate cancer patients. Until that happens, the medical community is unlikely to pay much attention. I'm also thinking that each scan - C11 acetate and feraheme USPIO - may be superior for certain purposes; there probably will be places for both.


Quote:
Since this is Prostate Cancer Awareness Month, it is a good opportunity to write to our legislators to exert pressure on the FDA to expedite approval of these contrast agents and to eliminate burdensome regulations. I'll get off my soapbox now.

- Allen
Thanks for your look at the conference presentations on these new imaging tools. I particularly appreciate some of the finer points that you clarified about the PET scans.

Take care,

Jim

 
Old 09-29-2011, 04:50 PM   #13
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Re: Going from incurable to likely curable!!!

Hi Rhonda,

I've just finished responding to Allen's post #4, which is relevant to your concerns here, but I also wanted to respond directly to your post #13 of 9/29. I'll put comments in green and leave out some of the previous exchange so this does not get too long. I'll put my previous comments that you quoted in blue. Your comments are in black.


Hi Jim,

Thank you for the detailed reply. I'll respond to what you've said below:

...
In my own case, I'm thinking that a lot of the Gleason grade 3 cancer I had has probably been eliminated.

I'm hoping that's true. Whatever the case may be, I find it very impressive that the Thalidomide is doing such a good job of keeping you off of Lupron and Bicalutamide for such an extended period of time!

Most of the work is done by just the triple blockade up front, with the thalidomide doing some mop-up work at the tail end of each vacation period. I'm thinking Irv may have an extended vacation, hopefully for years or indefinitely, based on a year or so of ADT3 and the Avodart for maintenance. Not many of us on IADT3 have done the thalidomide approach, but I believe it has merit. It has definitely worked for me.

There is now so much credible evidence that the two year forecast is simply wrong and highly misleading for many patients. The imaging and well-targeted radiation are real breakthroughs!

It sure gives a lot of hope. Is it Proton beam therapy that you're referring to? I'm wondering if the radiation available now would still be a huge risk for Irv of aggravating his colitis which has been in remission for about 8 years now. It wouldn't be very nice to trade off one problem for another very unpleasant one (like the idea of a colostomy...ugh).

I have been paying attention to results from the Dattoli Cancer Center (focused on prostate cancer) and from the radiation experts for prostate cancer in Seattle for some years. The Seattle folks are more focused on seeds, while Dr. Dattoli has worked with seeds and advanced IMRT with advanced image guidance. Moreover, he has now treated many patients with oligometastatic disease. That's probably where I would look for treatment if the feraheme imaging were favorable. However, Proton beam therapy, or perhaps another approach like Stereotactic Body Radiotherapy, probably would also be suitable if physicians expert in oligometastatic disease were available to do the planning and implementing. Colitis of course would be a potential hurdle.

... I hope that makes sense and that I don't sound overly negative. I can say that, in most cases, thanks to you, I feel very hopeful for the future, but, still, sometimes I need a helping hand of support to get me back up when I'm feeling a little down over this. ...

You're welcome. I'm glad that I and the Board have been able to help. You are helping me "pay it forward" for help I've received. To me the way you and Irv feel at this point, including the ups and downs, is quite normal.

... Well, if we have to incur the expense to go outside of Canada, we will. However, what is your opinion on this? Is this something we can hold off on? I'm guessing if Irv's vacation periods are extended, then the answer would be a resounding YES! However, if the cancer proves to be more aggressive than that, I wonder if following your route with several sessions of ADT3 before it stops working would be unwise before seeking out the scanning and possibility of radiation. Afterall, we still have to keep the colitis concern in mind. I'd appreciate your thoughts on this.

Yes, I'm convinced Irv will have success that will last for years if not indefinitely long. By then Canada may have what he needs for a follow-on, or something even better may have emerged. At the rapid pace of technological improvement for prostate cancer, I think that is quite likely.

That is the kind of recurrence that the new approach is apparently curing. It appears that up to five mets is a magic range - beyond that indicates wider spread disease that is difficult to cure, at least as of today.

That would be interesting to know. Irv didn't have a "recurrence" in the usual sense. His cancer was just never eliminated for any period of time after surgery. His PSA was never undetectable. The unanswered question would be, then, how long has the cancer been outside of the prostate? He had a unifocal positive margin and extracapsular extension, as well as seminal vesicle invasion. His first PSA check after surgery was 1.12. The doctor seemed to think that would indicate a high probability of systemic cancer.

Up to a few years ago virtually all doctors, as I understand it, including Dr. Myers and other leaders in treating advanced prostate cancer, would have also thought disease like Irv's was systemic, as did Irv's doctor. However, it now looks like a large proportion of those patients is free of systemic disease and has instead oligometastatic disease. It's by now means a sure thing. There is still a large proportion that does have systemic disease, but at least there is a well-based shot at a cure for many of the advanced patients. I'm convinced that many of those who cannot be cured can succeed in turning the disease into a "chronic" disease instead of a deadly disease. Up until a week ago, that had been my goal.

I'm hoping that cancer confined only to the lymph nodes around the pelvic area could account for that remaining PSA....and, if there are only 5 areas of metastasis or fewer, where could these areas be which would still offer hope of a cure? Is it possible, if they are found elsewhere in the body besides the lymph nodes, that there is still a chance of cure with radiation to those areas? Was any of this discussed in detail and would you happen to know the answers to these questions based on the information which was addressed at the conference?

What has been fairly recently learned is that there is a strong likelihood that the cancer has gone to just a few typical lymph node sites. It is unusual for it to have gone to other "soft tissue" sites such as the liver. However, my layman's impression is that radiation would sometimes be successful for mets in sites other than the lymph nodes.

... I'm not really clear on what you're saying here...Is it the Nilutamide which has the side effect on night vision and causing serious pneumonia? Or does the Flutamide also have those possible side effects?

My English teacher would not have been proud of that sentence where the "it" was unclear. I meant the Nilutamide. Flutamide has its own issues that need to be watched and managed if needed, but not problems with night vision or potential serious pneumonia as key concerns.

Also, what do you think of the idea of starting the hormone therapy again without bicalutamide and stay with it while the PSA declines and then, once you see a rise again, go back on the Bicalutamide and watch for a drop again? It worked in the case of one man who I read about. Then, if that is no longer effective, at that point switch to Flutamide. What's your thought on that?

It's credible to me that such an approach worked. Personally, with a dose of just 50 mg of bicalutamide now, I believe (as a layman but with personal experience that applies) that using bicalutamide and Avodart with the Lupron again would be better, switching to flutamide if the need arose. Of course, that question would be best addressed when it became a reality by an expert doc.

Yes. Time is often on our side. It's quite possible that in time a different approach, such as safely revving up the immune system, will prove highly curative.

Are you referring to treatments like Provenge here? I don't like what I've read that it extends life for only about 4 months...What's 4 months for $90,000? ....I don't get that logic. What am I missing? I prefer the idea of sensitive imaging and zapping the positive areas. I wonder if safer radiation for colitis patients will be available in the future...Again, it would be interesting to know your opinion on this.

Provenge is one immune system option, as is Leukine, but I was also thinking of a development we learned about at the conference. I hope to report about that shortly or add to Allen's report if he mentions it first.

As for the four months of added survival time that was documented for Provenge in the trials, while true, that's really a misleading number and too negative. As Dr. Mark Scholz emphasized at the conference, FDA Phase III trials are not designed to give us the most accurate picture of likely benefit to patients. Rather, they are designed to provide the best evidence that the FDA needs to decide whether to approve a drug/treatment/imaging system/etc. The two purposes are quite different. For instance, to get a superior idea of how truly effective a drug was, a trial would probably have to go on for quite a few years, which would greatly boost the expense and would also both delay approval of effective drugs and likely keep patients on ineffective drugs for long periods. In the case of Provenge, the trial designers estimated that tracking survival for up to three years would be sufficient to demonstrate a benefit (or a failure), and that proved out. However, as part of that plan, they only counted survival to the three year point; in other words, if a patient who had enrolled early survived for six years, his case in the trial was only credited with three years of survival. In fact, three times as many patients in the Provenge arm of the study were surviving at the three year point compared to patients in the other arm of the study. That's a dramatic difference! There's a lot more to that "four month" issue, which patients, the media, law makers and even many doctors have trouble understanding, but I hope this is enough for now. The situation for a successful drug is essentially usually much better than the approval trial suggests!


...More and more I'm thinking that it would be wise for Irv to have just one more injection to make it one year in the "on" phase before coming off the heavy duty drugs. The only situation that would make me question this is if we see an upturn in Irv's PSA before that (which I don't suspect, and hope, won't happen), in which case I think it would be good to eliminate the Bicalutamide and see what happens as a result of that. Even if it stays the same, at .03, I still think it would be good to hold it down for a few more months (one more injection) and then celebrate as he comes off and keep our fingers and toes crossed for a long "OFF" period maintained with Avodart....

I think your right in getting comfortable with just a year based on what I'm hearing and reading from the experts in hormonal therapy. I've had such success with longer periods that I'm biased toward more time, but longer time is probably not adding much if anything. Drs. Scholz and Lam, continuing with some patients from the former Strum/Scholz practice, found that continuing blockade beyond seventeen months added little if any benefit, and based on other information from other practices, they are learning toward on-therapy periods of about a year, as I see it. However, I'll bet they are tailoring their approaches to the way individual patients are doing, especially regarding the pattern of PSA decline and where their starting points and overall case circumstances. I suspect they would have wanted me to continue well beyond a year if they were looking at my first cycle of treatment but in 2011.

Take care,

Jim

 
Old 09-29-2011, 06:13 PM   #14
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Re: Going from incurable to likely curable!!!

Jim, one small point... You wrote:
Quote:
I'm thinking that the C11 acetate and the feraheme USPIO scans may be competing for the same imaging jobs.
My impression is that they may be somewhat complimentary. My understanding is that the feraheme is picked up by healthy cells in lymph nodes, but not by cancerous cells which don't seem to use iron. This makes healthy lymph nodes show up as black on an MRI, while cancerous lymph nodes stay white, just as on an ordinary MRI. I'm not sure how capable it is of imaging bone mets. The reason the FDA gave for turning down Combidex (which was also iron based) was because it had a high level of false positives -- many healthy lymph nodes failed to absorb the iron so they seemed to be positive for cancer. I'm hoping that feraheme has overcome that shortcoming.

Acetate and choline work the other way. They are metabolized preferentially by cancerous cells, so the C11 substituted versions glow in a PET scan and they show up particularly well in bone. The problem with C11 is the 20 minute half life, which makes it difficult because of the logistics of getting injected with a fresh hot sample. My impression is that choline is more strongly absorbed than acetate. The F18 versions also work, but fluorine substitution seems to affect the metabolism of those substances and is not taken up to the same extent.

If possible, I would want to have both tests done.

By the way, I presented an abbreviated version of some of my notes from the conference to my PC support group. I would be happy to post them, although I'm not sure how much sense they would make without further explanation. If you have your notes in a more comprehensible format, you can post those instead. What do you think?

- Allen

 
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Old 09-30-2011, 06:02 AM   #15
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Re: Going from incurable to likely curable!!!

Jim

With regards to the approach of USPIO plus RT of lymph nodes, I would recommend you to include in your researches this 2008 study from Michael T. Milano (Department of Radiation Oncology, University of Rochester Medical Center), which is of interest to your “not so far” treatment for oligometastatic cacer.
The origins for this clinical oligometastatic disease (as it is called) comes from an hypothesis idealized by Hellman and Weichselbaum (1995) which refers to a stage when a patient with a few number of detectable metastatic tumors/lesions, is considered to be in the transitional state between localized and systemic. Thought the study refers to breast cancer, the diagnosis process is similar and the treatment is radiotherapy. You can find the article by typing “oligometastases aboutcancer” in a web search engine.

Wishing you a smooth “drive” in your next journey.
Baptista

 
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