Chemo while low PSA

[Terje]

Dear brothers, I need some advise/ opinions!

I feel I am at a crossroads of sorts. Maybe I even have an opportunity!

So thinking 'out-of-the-box' I am considering doing chemo before what would be considered normal standard of care.

I have managed to drive my PSA down to 1.1 and in light of recent research showing early use of chemo therapy to extend life expectancy, I was wondering if this strategy might prove useful 8 years into the battle.

The idea being to hit the cancer over the head while it is 'weak' and I am relatively strong.

Background:

Diagnosed in 2008 age 54. PSA 7.8 with seminal vesicles involvement. This was followed with Radical prostatectomy 2008, radiation 2009, thereafter Lupron, Firmagon, Xgeva, Provenge 2013, Zytiga 2013 (still on it!), Xofigo 2016 (mets in shoulder and ribs), Lynparza 2016.

The PSA never went over 10.5. I have been diagnosed with a BRCA2 mutation, which is the reason I started with Lynparza (Olaparib). In addition I take daily supplements (Metformin, statin, vitamin D3 (10,000 iu), Wisconsin GinSeng and an Estradiol patch).

Would doing chemo now be a 'smart' decision? I feel I have little to loose and potentially maybe quite a bit to gain.

I would love to get some opinions.

Kind regards

Terje

[Dan59]

Terje, I don't think any of us knows for sure the answes to your question, as the new study is for early chemo. Though I have heard many experts say hit it with the hard stuff while the body is still strong, Please make sure the insurance approves as chemo is very expensive, did they pay for olaparib?. Were you receiving Olaparib in a study? Congratulations on being so on top of everything and keeping your cancer in check 8 years later, You have done well. Wishing you the best in the future.

Dan

[Terje in reply to Dan59]

Hi Dan!

Thanks for your response. I did not receive the Olaparib in a trial. My Oncologist applied through my insurance company. It was initially declined, but approved upon appeal. This process was repeated after 6 months.

I am on 'Obama care' as of 1/1/2017 so I am of course curious to see if they will approve it too.

[gusgold]

I would go on Xtandi first and see if you can drive PSA <.1....otherwise I would to the chemo

Gus

[Terje]

Thanks Gus!

My PSA has been declining every month since I started with the Lynparza (and it still is). However, I am pretty sure that at one point it will stop and start moving upwards again.

This could happen in one month or 1 year. I just like to have my options sorted out in advance. Xtandi is still in my arsenal. BAT sounds tempting. Itraconazole could also work for a while.

Research is making major strides so in the meanwhile we tweak and hang in there!

Terje

[Hidden]

I started chemo early but my condition was much more advanced than yours. My treatment was based on the E3805 trial. Quite a few men "miss out" on chemo because they wait until they are to weak to tolerate the treatment.

Of course, what do I know?

[Hidden]

Your treatment to date seems fairly careful.

You have metastatic cancer. Technically the CHAARTED trial was for those who were metastatic at diagnosis, but I think the extrapolation is commonly made.

In any case, chemo will be targeting a new subset of cancer cells, and so I think it is a good idea for you. Rather than pushing farther along the "hormone signalling" series of treatments, going at "cell division" makes sense to me.

Have you had any imaging beyond the standard T99 and CT? Do you know if the cancer is contained in a few pelvic lymph nodes, where surgery could lead to a cure? Or is the cancer scattered like dust throughout your body? Ie should you be looking to the "focal" or the "systemic" class of treatments?

[Terje in reply to Hidden]

Thanks Martingugino!

I very much appreciate your input. I like your point that chemo will target a new subset of cancer cells.

I haven't had any other scans besides the bone- and CT-scan.

[hadleycash]

Hi Terje, I too have BRCA2 aggressive prostate cancer, but not as far down the road as you. Gleason of 9, 4/5. Miniscule amount of 5 in pathology, but it still counts. Prostatectomy 2 years ago, seminal vesical invasion, PSA at 3.2 before surgery. Positive 1mm on left side, and multiple positive focal margins right sevinal vesical. Clinical trial 4 months later with rising psa. Trial was radiation therapy, Lupron for 6 months along with Xtandi. At trial start psa was .7, undetectable from one month in to three months after trial end. Doubling time has always been one month. PSMA PET scan three months ago revealed positive retro-peritoneal lymph node. Started on Lupron again 2 1/2 months ago. RPLND surgery last month to remove all retro-peritoneal lymph nodes. Pre-surgery PSA from 1.6 pre-Lupron to .10. Now as for you! I've done a ton of reading on BRCA2 linked prostate cancer... our key commonality. I looked at olaparib, as HDT doesn't tend work that well with BRCA linked PC. When my PC becomes castrate resistant, I plan on seeking out a clinical trial using tatazoparib. It's like the next gen PARP inhibitor since olaparib. One trial found it 200 times (not%) more effective in inducing apoptosis of BRCA linked cancer. It supposedly has less side effects than olaparib, and a lot less than chemo. I would check it out before turning to chemo, especially at your development stage.

[Hidden]

Yes. Never too late. I did a chemo trial almost 13 years ago immediately with the onset of mets and do not regret it one bit. It saved my life. Over the years I have posted my journey. Google Gourd Dancer Prostate Cancer.

Gourd Dancer

[Terje in reply to Hidden]

Thanks gourd_dancer!

I think I found some of the information you are referring to and indeed it supports my thinking that I should consider hitting the cancer while the tumor load is low and I feel relatively strong.

[Hidden in reply to Terje]

I benefitted from early chemo treatment and am a strong advocate. It only makes sense in tackling this bastard. Good luck.

GD

[Hidden in reply to Terje]

Early chemotherapy, as in when ADT begins, has been shown to produce better results with fewer side effects than waiting until ADT failure to take chemo. This goes especially for men with a "high" tumor burden. Definitions of a high burden of disease have included the presence of visceral metastases, a bone-metastasis burden categorized by site (beyond the axial skeleton) or by a high number of lesions, or a combination of these. There's a lot to digest about this whole topic in Sweeny, Carducci, Vogelzang NEJM 2015 Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer [CHAARTED] at nejm.org/doi/full/10.1056/N... .

It compares ADT alone to ADT + early chemo, but we've known for years that late chemo (i.e., after ADT failure) adds a lot of misery with very little extra heartbeat to show for it. OTOH, this study's Conclusion says "the combination of standard ADT and six cycles of docetaxel resulted in significantly [12-15 months!] longer overall survival than that with standard ADT alone in men with hormone-sensitive metastatic prostate cancer. The clinical benefit at this early analysis was more pronounced among patients with a higher burden of disease."

I've been strongly in favor for years of the many oncologists who advise postponing ADT until it makes us feel BETTER, but since my DT dropped from "like, forev-ver" to four months, I changed not only that tune but my chemo tune, too. (My chemo tune used to be "No way, Jose", but this and similar studies changed that tune, too.) OTOH, the longer we stay on taxotere, the longer we live ... but, my GOD ... the price it extracts from our QOL!

[JoelT]

Early chemotherapy has shown a survival benefit ONLY in men who are castrate sensitive, have very aggressive disease (Gleason 9 or 10) and multiple bone mets. Others did not have any benefit other than side effects. It is great if you have the type of cancer I described, otherwise stay with Zytiga or Xtandi at the appropriate time.

Joel

[Hidden in reply to JoelT]

I see that the CHAARTED study was for high-volume metastatic disease, so extension to other populations would be based on clinical judgement I think. Or is there a study that found that early chemo did not have an effect on Overall Survival for hormone sensitive patients?

If that is the case, then it suggests the speculation that chemo works mostly not on the naive cancer cell line but on the AR-multiplied and V7 lines.

I had Gleason 8 at Dx and (the vote) was unanimous to put me on ADT+chemo.

[JoelT in reply to Hidden]

In the E3805, a randomized controlled clinical trial that enrolled 790 men with metastatic prostate cancer between July 2006 and November 2012, all men received initial ADT, either ADT alone or ADT with docetaxel every 3 weeks for 18 weeks.

Results showed a significant improvement in the overall survival for men who received ADT plus docetaxel compared to ADT alone (3-year survival rates of 69.0% vs. 52.5%, respectively).

However, there is an important caveat as the majority of benefit was limited to men receiving both ADT and chemotherapy who had significant metastasis (3-year survival rates of 63.4% vs. 43.9%, respectively). As the result the investigators noted that the use of chemotherapy in combination with ADT should be limited to men with high-extent (multiple metastases) metastatic prostate cancer.

Joel

[Hidden in reply to Hidden]

I read what you posted as meaning that chemo was shown to be ineffective in those who are castrate resistant.

E3805 is the CHAARTED trial. The findings did not stratify a group of men who were castrate resistant nor a group who became castrate resistant during the trial. I don't see the basis for your claim.

nejm.org/doi/full/10.1056/N...

Nor did I see Gleason score mentioned in the finding. And of course the nature of the disease changes with treatment, so that the Gleason score at diagnosis will not adequately represent the disease later on.

[Magnus1964]

Whether than focusing on the PSA number itself watch the rate that your PSA is going up. If it doubles every 3 or 6 months and you have exhausted all other options then consider chemo

[AlanMeyer]

Hello Terje,

I don't know the answer to your question. I've followed Gourd Dancer's experience with early chemo and been greatly impressed by the results he achieved. However I've also seen the study that Joel refers to which might caution you against chemo.

In light of that, here's my advice:

You are considering an unconventional treatment approach. I think you need an expert to advise you. Try to find a real expert, a medical oncologist who specializes in prostate cancer and, ideally, works at a research hospital where keeping up with the latest research is a required part of the job. As I understand it, people like that are not necessarily any more expensive than oncologists in private practice at community hospitals. Get all your history, test results and all your questions together. Ask the expert's advice.

I wish you the best of luck.

Alan