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Mia99 01-10-2013 07:13 PM

Can't get PSA to zero
 
Diagnosis of husband's stage 4 PC in September, age 48. PSA was 348 at diagnosis. Dropped to 7 after 30 days of Lupron. On 12/5 PSA was up to 11; testosterone was 10. PSA just tested on 1/9 and it's 13; testosterone is 45. He is otherwise in good health.

Why are both going up?

What actions should we be taking? This is a very short time for lupron to stop working.

I hate to consider this, but is it a bad thing that he can still gain erections and ejaculate? Is this a sign that Lupron is not enough?

Thank you for any help you can offer.

Tall Allen 01-11-2013 01:03 AM

Re: Can't get PSA to zero
 
If he's got rising PSA on Lupron, he's a good candidate for Zytiga (abiraterone) or, better still, Xtandi (enzalutamide). Insurance might cover it if his PSA has been rising. Those are potent anti-androgens he would take along with the Lupron. Also, he can try switching to Firmagon instead of Lupron. Probably not a bad idea to add in Proscar or Avodart. Different medications may work for different guys, and thank God, there are more choices now than ever before.

You're right that best results are achieved from getting his PSA as low as possible. Testosterone should ideally be below 20. Maybe ask his doctor to check his DHT level too.

Hormone therapy acts more against libido than against erectile function. But if he feels like it, that's great that he can still enjoy that.

- Allen

Mia99 01-11-2013 03:51 AM

Re: Can't get PSA to zero
 
Thank you, and what should his DHT level be? How important is that and what does it indicate? It has never been tested.

Tall Allen 01-11-2013 11:16 AM

Re: Can't get PSA to zero
 
Finasteride (Proscar) can reduce DHT by 70% and Dutasteride (Avodart) by 90% from baseline levels, so it's useful to determine what the baseline is before such therapy begins. Because testosterone is metabolized into the more potent androgen DHT, Testosterone levels will rise when that metabolic pathway is blocked. DHT is much (5-10x) more potent at stimulating PC, so that's OK. It's often used together with a GnRH agonist (e.g., Lupron) or antagonist (e.g., Firmagon), and an anti-androgen (e.g., Casodex, Zytiga or Xtandi).

- Allen

Mia99 01-11-2013 11:39 AM

Re: Can't get PSA to zero
 
Thanks very much for setting me on track again.

Mia99 01-25-2013 01:38 AM

Re: Can't get PSA to zero
 
We may have been off track after all and I'm a little confused. The original levels (PSA 7, testosterone 10) were measured with tests ordered by the oncologist in October. Labs ordered a couple weeks ago showing PSA 15 and testosterone 45 were ordered by a second doctor (integrative medicine) and performed by a different lab. This week we were retested by the oncologist / original lab and results show PSA 17, testosterone 8.

I don't know where the testosterone result of 45 would have come from but the oncologist says it was wrong. He also says testosterone of 8 shows the lupron is suppressing production as it should, and that hormone therapy is failing.

I asked for DHT levels but we don't have the results back yet. The oncologist ordered this only to humor me. He says DHT has to be low if testosterone is low. He just left for ten days so when the results come back the office will contact me but I won't get an interpretation for awhile. Also he never checks DHT so I don't expect much insight. What are we looking for with DHT as far as levels and what will that indicate?

The oncologist also said that since hormone therapy failed so quickly (we began Lupron in late September, see my first post) that alternate hormone therapies are likely to fail. "This has taken a lot of bullets out of the arsenol" was his quote. He is sending us for a CT and bone scan next week and recommends chemo (Taxotere) next. As originally presented, chemo was to be an end- game treatment. Is that truly the next logical step, and nothing else is on the table?

Thanks for any insight...

Tall Allen 01-25-2013 11:28 AM

Re: Can't get PSA to zero
 
It's always a good idea to use the same lab for all your tests. Different test kits have differing sensitivities. As long as you pick one and stick with it, you're OK.

DHT should be suppressed as well. If it isn't, then the cancer is manufacturing DHT from a non-testosterone precursor (androstanedione) and Avodart may block that. Here is a technical reference that you can send to your oncologist. I've found that it often helps to provide such references from reliable sources (but [I]not[/I] from random internet sites) and doctors usually appreciate it when I do provide it.
[I]http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262939/[/I]

As I said before, Zytiga and Xtandi often continue to work [U]after[/U] castrate/Lupron-resistance sets in -- that's why they were developed. They are new and very expensive.

Zytiga (abiraterone) has been available for over a year but was originally only FDA-approved for use [I]after[/I] Taxotere (docetaxel) was tried. Just last month, the FDA approved it for use [I]before[/I] Taxotere.
[I]http://www.cancer.gov/ncicancerbulletin/121112/page8[/I]

Xtandi (enzalutamide) was just FDA-approved 4 months ago, and may be even more effective than Zytiga. Currently it is approved for use [I]after[/I] Taxotere. However the chemo pre-treatment requirement may be waived if in the opinion of the doctor [I]or[/I] the patient it might be detrimental to his health (I learned this tip from Dr. Scholz, btw). That said, your husband might want to go for a single cycle of Taxotere now anyway, just to get that requirement out of the way. Besides paving the way to get your insurance to pay for Xtandi, it may increase his eligibility for some clinical trials down the road. New drugs are usually tried first on men who are castrate-resistant [I]and [/I]have tried Taxotere.

- Allen

Mia99 01-25-2013 11:44 AM

Re: Can't get PSA to zero
 
Thank you, Allen, especially for the link about DHT to show the doctor. Maybe that link includes this answer but it's completely over my head... can you tell me what a normal DHT level should be, what level it should be while on Lupron, and what level might signal the need to add Avodart?

Tall Allen 01-25-2013 12:35 PM

Re: Can't get PSA to zero
 
When you get the lab test results back, it will show the normal range for that test kit. His DHT level should be below that. If it's not, why not see if Avodart brings it down? Ideally, it might have been useful to have had his own baseline DHT level taken before he started on ADT, so you could detect the degree of DHT inhibition from his ADT alone and by adding Avodart to the mix.

According to one source, normal levels are between 23-73 ng/dl (.8-2.5 nmol/L).
[This is based on the full text article available here: http://www.ncbi.nlm.nih.gov/pubmed/15901667]
But you should use the lab's definition of "normal" if they provide it.

- Allen

Mia99 01-25-2013 12:54 PM

Re: Can't get PSA to zero
 
great, thank you. It has been frustrating that doctors are getting no baselines. I had to ask for testosterone a month into the lupron treatment so we don't know the starting measurement for either. This is both locally and at Cleveland Clinic.

Tall Allen 01-25-2013 02:45 PM

Re: Can't get PSA to zero
 
I've dealt with many doctors over the years, and I wish I could say I've learned how to do it. Every doctor is different and has his own set of ego and personality issues, values, biases, and communication styles, just as we all do on the patient side too. It's a difficult relationship to negotiate when we might only interact for a furtive hour, yet no relationship we form outside of family and close friends is more important to our continued well-being. One thing I've found to be universally effective is learning to speak their language. It changes the whole dynamic. However, how many of us are able to do that? I've also learned to be very non-confrontational -- nothing gets those ego barriers up like a direct challenge. When I present research to them (usually via email so that they have time to look it over), I put it in the context of something like, "I saw this new study that you've probably already seen. What implications might it have for my treatment?" For me, it helps a lot if the doctor has a lot of academic curiosity (i.e., a nerd) although such people may have less developed social skills. Often, I find such doctors who are willing to work outside of the "standard of care" at major university hospitals and cancer centers with notable exceptions like Drs. Scholz, Lam, Myers, etc.

And then there's the battles with insurance companies... don't get me started!

I hope you will let us know if you have success getting Xtandi. If I had to pick one medication that's currently available that's worth fighting to get, that would be it. Zytiga's good too, and there should be no impediment to getting it now.

- Allen

Mia99 01-25-2013 02:54 PM

Re: Can't get PSA to zero
 
Good communication tips. I'll definitely post our progress.

Tall Allen 01-25-2013 05:41 PM

Re: Can't get PSA to zero
 
In case you decide to go for Taxotere, I forgot to mention that there's a new study out that shows that a reduced dose of Taxotere every 2 weeks is more effective and has fewer side effects than the traditional dose given every 3 weeks. You'll want to make sure your oncologist has seen it. Here's the reference:
http://www.ncbi.nlm.nih.gov/pubmed/23294853

Mia99 01-25-2013 05:52 PM

Re: Can't get PSA to zero
 
You are beyond priceless. As your message came in I was also reading something from Dr. Snuffy Myers saying he uses alpha lipoic acid in his patients as they start taxotere to reduce peripheral neuropathy.

For some reason I *finally* decided to seek out the writings of Dr. Myers. I might try to get an appointment with him -- he seems worth the travel.

Tall Allen 01-25-2013 07:36 PM

Re: Can't get PSA to zero
 
I think he is very innovative while still maintaining a grounded medical/science perspective - a great combination, imho. I can't think of any good reason to not consult with him, other than cost -- I don't think he accepts insurance. His book is somewhat out of date, though - knowledge and treatments have been accumulating rapidly in the past few years. There's no way that a print book can keep up.

Another doctor who has a similar reputation is Dr. Christopher Logothetis at MD Anderson in Houston. He's the Chairman of the Department of Genitourinary Oncology, and is very highly regarded in medical circles although he hasn't written a popular book as Dr. Myers has. It's just my layman's impression, but I think MD Anderson runs more clinical trials on innovative treatments for PC than just about anyone else.

I applaud your decision to seek out the opinions of the best, brightest and most experienced oncologists in the field.

- Allen


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