IADT question for VascodeGama

moonlitnight

Hi Vasco,

My husband has been on bicalutamide and degerelix since March. (Dx Feb with extensive bone mets and PSA of 32.)

His PSA dropped to a nadir of 0.24, then rose to 0.26 just before we took a trip for three weeks, i.e almost 6 weeks ago. On this trip, we stuck closely to his very strict diet/supplements and meds, but slipped a little on the diet and the supplements on occasion. On return, his PSA was 1.9 and his T. had tripled from 0.2 to 0.6.

His medical oncologist says to wait until the next blood test December 17 and if the PSA continues to rise, then he will stop the bicalutamide for a short period, during which time the PSA should likely drop back. In four months or so, it should begin to rise, and then he will put my husband on nilutamide. This isn't carved in stone and as far as he is concerned, we just need to take the time to see if it goes down as opposed to panicking.

Meanwhile, our very well respected naturopathic oncologist (in Canada, NDs are considered valuable members of the healing community), says he has seen considerably better outcomes in the case of metastatic and non-metastatic PCa, with IADT. He therefore suggests we give this real consideration despite the fact the nadir was never .005 or less. He is concerned as well for bone integrity, which of course suffers more with CADT. Neither oncologist believes that bisphosphonates are helpful in the long term and have undesirable risk factors such as ONJ. (I realize Strum says that this is largely due to not getting enough bone builders such as calcium, boron and so on.)

What puzzles me, and I will email the ND about this in case I misunderstood - is the fact said that the degerelix should likely not be discontinued. This ties in with what the MD says concerning just stopping the bicalutamide. (Degerelix has a different MO from leuprolide in that it is antagonistic.)

So, with your vast experience and expertise, do you have any knowledge of what exactly is stopped during IADT? Is it both drugs, or just the antiandrogen, bicalutamide?

Thank you... MLN

 

VascodaGama

IADT

Moonlitnight (MLN)

You are anxious and I would repeat and answer to you with your words above; “… take the time to see if it goes down as opposed to panicking…”

In fact the PSA could be expected to increase in your husband’s case due to his advanced “extensive bone metastases”, you have described in your previous thread. The ADT2 protocol (Firmagon plus Casodex) administered by his doctor also does not include a “direct” attack on the cancer in bone;
http://csn.cancer.org/node/262166

As I commented in your previous thread, I think it better to look for drugs that target the metastases in bone, such as Xgeva (Denosumab) or Xofigo (Alpharadin). They address the effects of osteoblast whish condition is “helping” the cancer to survive. Surely castration affects cancer survival but not all cancer depends on testosterone, particularly the PCa cells that mutate their ARs or “learn” to produce their own androgens. This is a process addressed with drugs like Xtandi (a “refined” androgen receptor antagonist drug) which activity is dedicated to the intratumoral effect.

In bone metastases cases, LHRH agonists (Lupron) or antagonists (Firmagon) seem not to be as relevant as the work of antiandrogens in treating the condition because they only lower the testosterone circulating in the body. They only affect cancer that is testosterone dependent. Even so, when cancer progresses in refractory cases, doctors typically continue to administer these blockers for two reasons: 1) to continue the castration status and 2) because their use in combination with other drugs (in refractory cases) gave better rates of survival in trials.

When the PSA of a ADT2 patient increases while in castration, doctors usually increase the power of antiandrogens (ex; 50mg to 150 mg/day) or change medications of the same purposes (ex; degarelix to leuprolide; bicalutamide to nilutamide, etc.) this is your husband’s doctor principle too.

Stopping antiandrogens is done in refractory cases because cancer starts feeding on the drugs. Antiandrogens are made with similar bio structures of testosterone which facilitates the purposes of getting the drug to be stacked to cell’s ARs (avoiding the feeding), but it becomes “food” in plenty when the cells mutate their ARs to absorb it as a “modified” androgen.

The schedule proposed by the doctor refers to what is called Antiandrogen Withdrawal Response. This is a period when the cancer looses activity for the lack of the fake androgen (bicalutamide in your husband’s case) verified by a lower PSA, which then is followed by a constant increase indicating that the cancer started to “produce” its own androgens.
At such stage patients usually are moved to a second line of hormonal drugs and/or chemo therapy. An example is Zytiga and Ketoconazole. Some patients are recommended to immunological treatments like Provenge and the many just get into clinical trials where they (luckily) have the opportunity of experiencing newer drugs which would be prohibitive otherwise.

Regarding your inquire about the Intermittent approach in hormonal therapy (IADT), this is probably not proper in your husband’s case due to the bone mets. I know that Myers, Scholz, Strum, etc., only indicate intermittent approaches to patients that manage to get into PSA remission levels of less than 0.05 ng/ml, and did keep such levels during a period of 12 months, before going off-drugs.
Dr. Leibowitz (Bob) is the only oncologist I know that used IADT in patients of higher PSA levels keeping them also out of castration but they were treated with his “Antiangiogenic cocktails” (protocols), individually prepared. Here are links to the above;
http://www.compassionateoncology.org/publications.php
http://www.compassionateoncology.org/home.php

He is also one of the pioneers in the intermittent modality of administration of hormonal drugs. I am not so sure if Dr. Lam would follow Dr. Leibowitz protocols but you should inquire when visiting him.

As far as I know IADT is followed with the purposes of getting a patient out of castration and into normalcy. To such extent one should stop administering LHRH agonists or antagonists so that the body recuperates and the testicles start receiving the signalling to produce testosterone. Out of clinical castration is considered when the testosterone reaches levels above 0.50 ng/ml (50 ng/dL). Testosterone is required in other body functions too so that one is healthier and that is part of the benefits to stop the medication. In my experience the side effects of hypogonadism subsided along the increasing period of T. I am now with a T of 490 ng/dL and totally symptomless. Nostalgic libido is 100% back. 

I would like to recall you that I am not a physician. I have a keen interest and enthusiasm in anything related to prostate cancer, which took me into researching and studying the matter since 2000 when I become a survivor and continuing patient.
You may get better answers from your husband’s team of doctors.

The PSA at 1.9 ng/ml is still low if we take into account the bone metastases. The testosterone at 0.6 (I think you mean ng/ml) indicates that Firmagon has loosened its effects and such could be behind the increase of the PSA. I wonder if your husband has stopped taking the shots.

Hope for the best and be confident. There are many drugs and target medications to arrest the bandit and treat your husband even if he become refractory to antiandrogens. The list of supplements you indicated before seems to be excellent. I would continue taking them unless these interfere with the treatment. Here is another link related to diet;
http://cancer.ucsf.edu/_docs/crc/nutrition_prostate.pdf

Hopefully other guys here can feed in their experiences and opinions to help you. 

Best.

VGama 

moonlitnight

VascodaGama said:

IADT

Moonlitnight (MLN)

You are anxious and I would repeat and answer to you with your words above; “… take the time to see if it goes down as opposed to panicking…”

In fact the PSA could be expected to increase in your husband’s case due to his advanced “extensive bone metastases”, you have described in your previous thread. The ADT2 protocol (Firmagon plus Casodex) administered by his doctor also does not include a “direct” attack on the cancer in bone;
http://csn.cancer.org/node/262166

As I commented in your previous thread, I think it better to look for drugs that target the metastases in bone, such as Xgeva (Denosumab) or Xofigo (Alpharadin). They address the effects of osteoblast whish condition is “helping” the cancer to survive. Surely castration affects cancer survival but not all cancer depends on testosterone, particularly the PCa cells that mutate their ARs or “learn” to produce their own androgens. This is a process addressed with drugs like Xtandi (a “refined” androgen receptor antagonist drug) which activity is dedicated to the intratumoral effect.

In bone metastases cases, LHRH agonists (Lupron) or antagonists (Firmagon) seem not to be as relevant as the work of antiandrogens in treating the condition because they only lower the testosterone circulating in the body. They only affect cancer that is testosterone dependent. Even so, when cancer progresses in refractory cases, doctors typically continue to administer these blockers for two reasons: 1) to continue the castration status and 2) because their use in combination with other drugs (in refractory cases) gave better rates of survival in trials.

When the PSA of a ADT2 patient increases while in castration, doctors usually increase the power of antiandrogens (ex; 50mg to 150 mg/day) or change medications of the same purposes (ex; degarelix to leuprolide; bicalutamide to nilutamide, etc.) this is your husband’s doctor principle too.

Stopping antiandrogens is done in refractory cases because cancer starts feeding on the drugs. Antiandrogens are made with similar bio structures of testosterone which facilitates the purposes of getting the drug to be stacked to cell’s ARs (avoiding the feeding), but it becomes “food” in plenty when the cells mutate their ARs to absorb it as a “modified” androgen.

The schedule proposed by the doctor refers to what is called Antiandrogen Withdrawal Response. This is a period when the cancer looses activity for the lack of the fake androgen (bicalutamide in your husband’s case) verified by a lower PSA, which then is followed by a constant increase indicating that the cancer started to “produce” its own androgens.
At such stage patients usually are moved to a second line of hormonal drugs and/or chemo therapy. An example is Zytiga and Ketoconazole. Some patients are recommended to immunological treatments like Provenge and the many just get into clinical trials where they (luckily) have the opportunity of experiencing newer drugs which would be prohibitive otherwise.

Regarding your inquire about the Intermittent approach in hormonal therapy (IADT), this is probably not proper in your husband’s case due to the bone mets. I know that Myers, Scholz, Strum, etc., only indicate intermittent approaches to patients that manage to get into PSA remission levels of less than 0.05 ng/ml, and did keep such levels during a period of 12 months, before going off-drugs.
Dr. Leibowitz (Bob) is the only oncologist I know that used IADT in patients of higher PSA levels keeping them also out of castration but they were treated with his “Antiangiogenic cocktails” (protocols), individually prepared. Here are links to the above;
http://www.compassionateoncology.org/publications.php
http://www.compassionateoncology.org/home.php

He is also one of the pioneers in the intermittent modality of administration of hormonal drugs. I am not so sure if Dr. Lam would follow Dr. Leibowitz protocols but you should inquire when visiting him.

As far as I know IADT is followed with the purposes of getting a patient out of castration and into normalcy. To such extent one should stop administering LHRH agonists or antagonists so that the body recuperates and the testicles start receiving the signalling to produce testosterone. Out of clinical castration is considered when the testosterone reaches levels above 0.50 ng/ml (50 ng/dL). Testosterone is required in other body functions too so that one is healthier and that is part of the benefits to stop the medication. In my experience the side effects of hypogonadism subsided along the increasing period of T. I am now with a T of 490 ng/dL and totally symptomless. Nostalgic libido is 100% back. 

I would like to recall you that I am not a physician. I have a keen interest and enthusiasm in anything related to prostate cancer, which took me into researching and studying the matter since 2000 when I become a survivor and continuing patient.
You may get better answers from your husband’s team of doctors.

The PSA at 1.9 ng/ml is still low if we take into account the bone metastases. The testosterone at 0.6 (I think you mean ng/ml) indicates that Firmagon has loosened its effects and such could be behind the increase of the PSA. I wonder if your husband has stopped taking the shots.

Hope for the best and be confident. There are many drugs and target medications to arrest the bandit and treat your husband even if he become refractory to antiandrogens. The list of supplements you indicated before seems to be excellent. I would continue taking them unless these interfere with the treatment. Here is another link related to diet;
http://cancer.ucsf.edu/_docs/crc/nutrition_prostate.pdf

Hopefully other guys here can feed in their experiences and opinions to help you. 

Best.

VGama 

Thanks VDG

Thanks so much VDG. I an aware you are not a physician but my belief is that many members of the non-physician community have more to offer than some physicians.

Our MD oncologist would likely not recommend IADT as he goes along with "standard of care." He and our naturopathic oncologist know each other well and both trained under one of the most respected oncologists in Canada (now retired). The naturopath is a firm believer in IADT even when there are extensive metastases, based on his experience with over 5,000 patients.

I am just digesting everything you have written and will check the refs. Neither doctor considers the increase in PSA anything to panic about since the T has gone up and PSA cannot be produced without T.

My husband has been very regular with his monthly Firmagon shots and takes 50mg of bicalutamide and .5 a tablet of finasteride daily, with metformin.

I asked about something for the bone lesions but the doc said he should just carry on with his supplements and exercise for the moment. I find the way this disease is treated in the US to be very different from up here.  I believe you mean that the Xvega inhibits osteoclast activity. I have read Strum's latest book and put my husband on all the natural methods of supporting osteoblast activity while attempting to suppress the activity of osteoclasts.

I am going to ask the MD oncologist to switch to Lupron as the naturopath way prefers its effects and outcomes. Again, my deepest thanks.

moonlitnight

moonlitnight said:

Thanks VDG

Thanks so much VDG. I an aware you are not a physician but my belief is that many members of the non-physician community have more to offer than some physicians.

Our MD oncologist would likely not recommend IADT as he goes along with "standard of care." He and our naturopathic oncologist know each other well and both trained under one of the most respected oncologists in Canada (now retired). The naturopath is a firm believer in IADT even when there are extensive metastases, based on his experience with over 5,000 patients.

I am just digesting everything you have written and will check the refs. Neither doctor considers the increase in PSA anything to panic about since the T has gone up and PSA cannot be produced without T.

My husband has been very regular with his monthly Firmagon shots and takes 50mg of bicalutamide and .5 a tablet of finasteride daily, with metformin.

I asked about something for the bone lesions but the doc said he should just carry on with his supplements and exercise for the moment. I find the way this disease is treated in the US to be very different from up here.  I believe you mean that the Xvega inhibits osteoclast activity. I have read Strum's latest book and put my husband on all the natural methods of supporting osteoblast activity while attempting to suppress the activity of osteoclasts.

I am going to ask the MD oncologist to switch to Lupron as the naturopath way prefers its effects and outcomes. Again, my deepest thanks.

My husband, who feels and

My husband, who feels and looks as fit as can be, just got his test results back...Nadir was 0.24 in August. In November, it shot up to 1.9 and today, one month on, it is 3.2.

Also the Alkaline phosphatase is rising rapidly. He is on bicalutamide and Firmagon. Onc. said last month, if the PSA continues to be up on today's test, he will pull back the bicalutamide, but what will this achieve exactly? I think he should be on Xtandi, which is available up here in Canada. Just found out he is on vacation for tomorrow's visit, and that his partner will see us instead. Any suggestions? I feel I have to press for something as "pulling back on bicalutamide" seems to be rather feeble.

MLN

moonlitnight

moonlitnight said:

My husband, who feels and

My husband, who feels and looks as fit as can be, just got his test results back...Nadir was 0.24 in August. In November, it shot up to 1.9 and today, one month on, it is 3.2.

Also the Alkaline phosphatase is rising rapidly. He is on bicalutamide and Firmagon. Onc. said last month, if the PSA continues to be up on today's test, he will pull back the bicalutamide, but what will this achieve exactly? I think he should be on Xtandi, which is available up here in Canada. Just found out he is on vacation for tomorrow's visit, and that his partner will see us instead. Any suggestions? I feel I have to press for something as "pulling back on bicalutamide" seems to be rather feeble.

MLN

Vasco's reply

ARM problem and Gene mutations

 

MLN

Naturally you are upset and worried with this increase. This may confirm what we discussed in your previous thread. , Most probably your husband is experiencing ARM and now the cancer is feeding on the bicalutamide. That is why his doctor wants to stop him from taking the drug.
I think you should keep posting in the same thread to understand the chronology of events and compare it with the opinions you have received. It will cause you less stress. Here are your links;

http://csn.cancer.org/node/264806
http://csn.cancer.org/node/262166

As commented before, your husband should change the treatment protocol. Xtandi is better and more affinity to address the ARM (androgen receptor mutations) problem and it would substitute bicalutamide in his present protocol. Before changing, thought, he may try increasing the power of the drugs, exchange to drugs of similar purposes or start with a second-line HT adding Ketoconazole (or similar). Just discuss on the above with your oncologist on your next visit.

The effects of ARM may also address any constringency in your husband’s PCa cells in absorbing a medication he is now taking. This can be checked through a gene profile test that will follow the activity of the drug been administered or to be taken in the future treatment. Here you got the link for a study involving genes and ARM in progressive cases;
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2699836/
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC49492/

The researchers opinions says this: “…screening patients for AR mutations following hormone therapy failure, so that subsequent treatment could be adjusted accordingly. Understanding of how AR mutations alter androgen signaling at the molecular level will also be useful in the development of novel therapies, in particular Selective Androgen Receptor Modulators (SARMs). Knowledge of how such molecules affect the structure of the AR, interactions that the receptor makes and subsequently gene expression could aid in designing drugs that regulate certain subsets of genes. For example, it would be desirable to design a SARM that blocks expression of androgen target genes that promote tumour growth, whilst up-regulating transcription of beneficial genes (for example those important for maintenance of bone density)”.

Here you have a link to PCRI site about the treatment of HRPC patients which could be the diagnosis been given at this moment by the doctor of your husband. It is well described and probably would be recommended by Dr. Lam; (have you consulted him already?)
http://prostate-cancer.org/newer-concepts-in-the-treatment-of-hormone-refractory-prostate-cancer-with-bone-metastases-combinations-of-bone-seeking-radiopharmaceuticals-and-chemotherapy/

 

The rise of Alk could be due to any interaction of the supplements with the drugs. Better to get a prompt reply from his nutricionist. Care with Anemia.

Best wishes.

VGama 

moonlitnight

moonlitnight said:

Vasco's reply

ARM problem and Gene mutations

 

MLN

Naturally you are upset and worried with this increase. This may confirm what we discussed in your previous thread. , Most probably your husband is experiencing ARM and now the cancer is feeding on the bicalutamide. That is why his doctor wants to stop him from taking the drug.
I think you should keep posting in the same thread to understand the chronology of events and compare it with the opinions you have received. It will cause you less stress. Here are your links;

http://csn.cancer.org/node/264806
http://csn.cancer.org/node/262166

As commented before, your husband should change the treatment protocol. Xtandi is better and more affinity to address the ARM (androgen receptor mutations) problem and it would substitute bicalutamide in his present protocol. Before changing, thought, he may try increasing the power of the drugs, exchange to drugs of similar purposes or start with a second-line HT adding Ketoconazole (or similar). Just discuss on the above with your oncologist on your next visit.

The effects of ARM may also address any constringency in your husband’s PCa cells in absorbing a medication he is now taking. This can be checked through a gene profile test that will follow the activity of the drug been administered or to be taken in the future treatment. Here you got the link for a study involving genes and ARM in progressive cases;
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2699836/
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC49492/

The researchers opinions says this: “…screening patients for AR mutations following hormone therapy failure, so that subsequent treatment could be adjusted accordingly. Understanding of how AR mutations alter androgen signaling at the molecular level will also be useful in the development of novel therapies, in particular Selective Androgen Receptor Modulators (SARMs). Knowledge of how such molecules affect the structure of the AR, interactions that the receptor makes and subsequently gene expression could aid in designing drugs that regulate certain subsets of genes. For example, it would be desirable to design a SARM that blocks expression of androgen target genes that promote tumour growth, whilst up-regulating transcription of beneficial genes (for example those important for maintenance of bone density)”.

Here you have a link to PCRI site about the treatment of HRPC patients which could be the diagnosis been given at this moment by the doctor of your husband. It is well described and probably would be recommended by Dr. Lam; (have you consulted him already?)
http://prostate-cancer.org/newer-concepts-in-the-treatment-of-hormone-refractory-prostate-cancer-with-bone-metastases-combinations-of-bone-seeking-radiopharmaceuticals-and-chemotherapy/

 

The rise of Alk could be due to any interaction of the supplements with the drugs. Better to get a prompt reply from his nutricionist. Care with Anemia.

Best wishes.

VGama 

Pulled off bicalutamide. Our

Pulled off bicalutamide. Our oncologist has taken my husband off the bicalutamide for a couple of months. I asked about Xtandi but at the moment it is self-pay in Canada as the ACCESS trial completes this month   and it's not covered by the medical system (yet). Also, his T has dropped from 0.6 to 0.2. .