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Abiraterone/zytiga for hormone sensitive PCa

desperate for hope
Posts: 44
Joined: Oct 2016

Two clinical trials published in the New England Journal of Medicine reported significant improvements in progression free and overall survival of men with newly diagnosed metastatic, high risk and node positive men. 

http://www.nejm.org/doi/full/10.1056/NEJMoa1702900

http://www.nejm.org/doi/full/10.1056/NEJMoa1704174

My husband (61 yrs iPSA 28 pT3bN1M0 GS9) is not exactly "newly" diagnosed as he's been on continuous ADT for 9 months (since dx) and has had RP and aRT. His prognosis is not good. 

We've discussed adding abiraterone/zytiga to his ADT and the urologist has offered to write a prescription, saying that "it would not be unethical to do so." The only question is whether he should stop hormones to see if his PSA is undetectable because if it is, he may not need any ADT for a few years. 

It's a difficult decision and a risk either way. 

Has anyone on long term ADT disccussed adding zytiga with their physicians since the studies were published? 

Thanks!

 

Max Former Hodgkins Stage 3's picture
Max Former Hodg...
Posts: 3323
Joined: May 2012

Zytiga and Jevtana are usually employed post-Taxane failure. That is, after the common chemotherapy drug Taxotere or other Taxane agent has stopped working. But it is approved for earlier use, and such use seems to be becoming more popular among medical oncologists.

You mentioned "his urologist."  MOST urologists are NOT medical oncologists; a few are.  In his situation, I would suggest that he STRONGLY needs for his lead doctor to be a MEDICAL ONCOLOGIST.  As I said, these are not ordinarily the same thing, except in exceptional, multi-board certified individuals.

Beyond that, I have no slavage therapy expertise, but many of the guys here do, and I'm sure they will write.

desperate for hope
Posts: 44
Joined: Oct 2016

Thanks for your comment Max. I should have clarified- he's a urology-oncologist. They wear two hats around here in Canada. I think when men become castrate resistant they move on to an oncologist. 

Max Former Hodgkins Stage 3's picture
Max Former Hodg...
Posts: 3323
Joined: May 2012

desperate,

I am not a person knowledgable in the art of playing HT against metastatic disease, but several guys here are, and I hope they comment.

I do know that HT is commonly used and then backed off, and then begun again, to get maximum long-term benefit, but the when or why in this is not something I have studied.  I did read a study this year that said Zytiga begun earlier than it used to be has shown dramatically improved results, but I don't recall where that study was -- it might well be the same study that you linked above.

max

desperate for hope
Posts: 44
Joined: Oct 2016

Yes, I'll bet it was the NEJM article that you heard about. I read that this trial reported the greatest improvement in cancer outcomes of a clinical trial of ANY trial for ANY cancer of all time. 

I know about intermittent HT but with gleason 9, seems like you're playing with fire. It's not a kitten that you're releasing from its cage when you let PSA rise, but rather a wild tiger. I might be wrong, but that's how it seems. The problem is that a relatively small portion of men with PCa have GS 9 or 10 so there's not a lot of studies. 

I've accepted that because the family doctor chose not to offer or discuss PSA screening, my husband will die from PCa. My hope is to avoid suffering for as long as possible. 

 

Max Former Hodgkins Stage 3's picture
Max Former Hodg...
Posts: 3323
Joined: May 2012

Desperate,

Know that there is likely a lot of hope in store for your husband. YEARS..... HT allows men to survive a long time.  I had two friends from work die of Pca over the last 10 years or so.  Both lived 13 years after diagnosis with metastatic disease, an eternity, compared to most other types of cancer.  And both had good quality of life; the first 11 or 12 years were active, fulfilling times for both. The last year was ugly, to be blunt.  One used Zytiga and Jevtana; the other died before they were available.  I remember when one of them had his PSA go over 1,000. Chemo then dropped it to about 300, and it was like he was cured inour opinion. Odd, celebrating a PSA of 300, but it probably gave him close to a year, even in that situation. I recall that his PSA climbed from 60 to around 600 in about 6 months once, when the disease got severe and was ravaging him.  Another friend, cured from PCa years earlier via surgery, told me once over the phone, "He got his numbers wrong. There is no such thing as a 600 PSA." But there is.   I have seen men here report PSAs of 1,200, and read of a man in a journal that was in my urologist's office who hit 3,000 once and lived.  How, it's hard to imagine.

You absolutely do not know what tomorrow holds for him or you, what tomorrow will bring in new advancements. But there is reason to believe that tomorrow will be a good day for the both of you,

max

desperate for hope
Posts: 44
Joined: Oct 2016

Max, your words are comforting. I don't know why, but I need to plan for the worst and hope for the best. My husband has G9 and every negative pathology feature. The only positive news (I think it's positive) is that he's tested negative for a slew of genetic mutations including BRCA1/2. 

90% of the non-metastatic men did not progress for over 4 yrs with Zytiga (based on the study). I figure if we can get to 4 yrs without progression, there might be a new drug out. We are unlikely to get funding for Zytiga though, and will have to pay out of pocket. 

 

VascodaGama's picture
VascodaGama
Posts: 3041
Joined: Nov 2010

Desperate,

I am sorry for the situation. I applaud you for the researches you are doing to help your husband, however, I think that his doctor's opinion is the best for the moment. Probably your husband present HT protocol is sufficient to hold the bandit without the need of further intervention at the moment. Surely one risks deterioration in other health issues (side effects) if the HT is administered continuously in long periods (over three years), that also may cause earlier setting of treatment refractory.

Zytiga is just another drug in the HT arsenal to fight the bandit. It can be used alone or in combination with the drugs he is taking but earlier intervention with Zytiga would not alter his disease status. Traditionally this is administered as a second-line therapy providing further control on the advancement of the disease. If taken in combination with other HT drugs the quality of life of the patient deteriorates because it adds side effects to the ones already established, causing further suffering. In other words, one may get an earlier better control but such can be expected to fail earlier too.

In fact, the hormonal therapy tries extending the control, in sequential approaches using several ways to block androgens from reaching the cancer (its feeds on the stuff). Some interfere with the manufacturing of the testosterone and some interfere in the way that cancer absorbs it. Lupron and Zytiga are of the first group. Lupron stops the factory of testosterone (the testis) and Zytiga interferes in T manufacturing from cholesterol. Antiandrogens like Casodex and Xtandi (another second-line HT drug) interfere at cells AR receptors (the mouth of the bandit) avoiding these from absorbing the stuff. The therapy works well for a number of years until one becomes refractory.

Intermittent methods in taking these drugs seem to provide control while allowing periods free from the drugs side effects, improving the quality of living of the patient. It also fakes the cancer making it to cause refractory much later. You may know that refractory of HT drugs occurs when the cancer start producing its own androgens due to the lacking of it, for survival purposes, therefore becoming independent of the testosterone produced naturaly.
Zytiga manages to prolong the efficacy of HT because it also manages to interfere in the manufacturing process used by the bandit to produce its own androgens. This is one of the reasons why the drug is reserved for using after refractory sets in the initial therapy.

Intermittent approach also provides a period of recovery by the other body systems that use androgens for its activities. The testosterone is essential in bone formation, muscle activity (any tiny muscle in the body like the heart, etc) and in the general health and well-being status of other organs. It prevents osteoporosis.

The studies you refer in your initial post indicate that Zytiga can be used as prime HT successfully, meaning that one can use its blockade characteristics at the bigining of the hormonal treatment, instead of other methods of blockade. It does not imply that it substitutes the other drugs but that it complements the treatment.

Best wishes in his journey.

VGama

desperate for hope
Posts: 44
Joined: Oct 2016

VGama, 
i appreciate your contribution and I believe that what you wrote applies to the majority of men who are on long term ADT post RT. 

However, if  you examine Figure 1- Graph F, you will see that by 3 years, approx 30% of men on ADT alone progress in their cancer. (PSA rises, or something found on scans). My husband has heavy odds of being in that unfortunate group. 

He is GS 9, iPSA 28, pT3b sv+ ece, pos margins, bilateral lymph nodes + and cancer had invaded into the muscle of his bladder neck. His prostate was large and 70% was invaded by cancer.  In addition, only a limited PLND was done (high liklihood of more malignant nodes) and the dosage of his aRT was only 66 gys (they refused to do more). The only hope he has is that he has tested negative for about 15 of the most commom gene mutations. 

It seems to me that he stands a very good chance of being a guy that progresses early. In fact, he very likely has bone mets that haven't been discovered yet because they are too small. (no PET done).

Saving Zytiga till the end (if it works at all) is a 4 month prolongation of life, isn't it? Zytiga + ADT now, gives him his best chance of no progression for a few years. Hopefully, our son will be finished high school and be away at university when the real nightmare of this disease begins. 

 

GeneRose1's picture
GeneRose1
Posts: 64
Joined: Aug 2016

On a really practical side, Zytiga is crazy expensive (around $10K a month out of pocket). The issue is that this new treatment has not been approved by the FDA and, thus, insurance companies won't cover it. I brought up combining Zytiga with my current treatment (Lupron injections) with my Medical Oncologist and the gist is that until it's approved, it would be more cost-effective to stay the course with Lupron and then wait and see if the FDA approves using Zytiga in the first line of defense. Of course, more clinical trials are in the works to confirm and verify these findings and it might be worth your while to look into that. That would be a way to work around the cost.

desperate for hope
Posts: 44
Joined: Oct 2016

Thanks for your comments GeneRose, 

Who knows,  it might take a year for Zytiga to be approved. Not sure about your man, but mine can't risk it. 

A phase 2 study reported that if Zytiga is taken alongside a low fat breakfast, only 1/4 of the dose is required and that means 1/4 of the price!

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