Looking for input on changing treatment based on BRCA2 mutation:
My husband just completed 4th infusion of Doectaxal, with which he’s had a fluctuating psa
Prior to chemo 2.6
Post 1st Infusion 2.9
Post 2nd infusion 1.4
Post 3rd Infusion 1.6
He is also on lupron.
Began treatment May 18th
Initial PSA around 20. Had been coming down about 50% a month prior to chemo.
Thank you in advance for sharing your awesome knowledge with all who follow this forum!
You may want to discuss adding carboplatin to his next infusion. It seems to improve response over a taxane alone in men with a BRCA mutation. Afterwards, he can follow-up with a PARP inhibitor on a clinical trial. The FDA has given niraparib a "breakthrough therapy" designation, so it may be approved soon:
pcnrv.blogspot.com/2019/10/...
Here's a list of clinical trials:
pcnrv.blogspot.com/2018/02/...
He should be able to get carboplatin without a clinical trial.
Hi Allen, can you share the research where it says carboplatin might be effective for BRCA2? On my father's genetic report it says carboplatin would be low effectiveness for him... I wil ask them why with the research you will share with me. Thanks! Juliane
The cross sensitivity and limited or lack of cross resistance of PARP inhibitors and platinum chemo have been found in ovarian cancer:
ascopubs.org/doi/10.1200/JC...
clincancerres.aacrjournals....
cancerres.aacrjournals.org/...
sciencedirect.com/science/a...
And there is evidence it occurs in prostate cancer:
sciencedirect.com/science/a...
There are several clinical trials of carboplatin for BRCA2 mutation carriers:
pcnrv.blogspot.com/2018/02/...
The hope is that PARP inhibitors can be used as a maintanance therapy after treatment with carboplatin.
Thanks Allen!
Thank you for the thoughtful response Tall_Allen. We talked to the oncologist this morning and he is adding Carboplatin to the next round. In addition to BRCA2 there are least 2 other repair defects present so helpfully the DNA targeted drugs will work.
Hi Dachshundlove,
Long time no see, nice to hear from you again.
The Docetaxel does not seem to be doing much. Psa is not going much lower after 4 shots. the ADT prior seems to have done most of the work to get Psa lower, but it mainly slows down the Pca without killing many Pca cells.
I could not advise what might be best myself, but Tall Allen has more ideas than I do, and the idea of a PARP inhibitor could be tried, and it seems your man has time plus a low Psa to allow some experimentation. It will take time to begin PARP therapy, so a dose of carboplatin could be had. But as far as I know, platinum based chemo side effects are worse than taxane based chemo.
It seems the only other thing which might work could be Lu177, but that depends in getting a PsMa Ga68 PET/CT scan which may show if lu177 could ever be used.
I had Psa 25 before Lu177 began last Nov, it was 1.6 No 4 shot last May, and Lu177 gave big Psa reduction, and also Xtandi was added after No 3 shot. Psa was 0.4 a month ago, still reducing, and docs said I had no mets that did not have PsMa avidity in the last PsMa follow-up scan. So far so good. But Psa may rise again, maybe I get more Lu177, or if another scan shows low PsMa avidity I might have PARP if DNA test shows I am Brca2 positive, and I bet I am, because I had sister with Oa, other sister with Brca but survived, dad with melanoma, and his hum died at 55 with Oa or Brca.
To get into trials may prove difficult because researchers have conditions to be met, and not all can get the trials. Here in Australia, carboplatin and all other chemo is free in Medicare funded public hospitals but I have to pay full costs of Lu177 and the scans, and for DNA analysis and PARP. Someone mentioned olaparib might be used.
There are trials going on here for Lu177 combined with other things, and one is for Lu177 with Xtandi, but I am doing that anyway, after a research doc said it should work. The lady research doc is doing the Lu177 + Xtandi trial now to verify whether she was right about it working better than just having Lu177 alone.
But it now looks like I might last another 3 years+ alive with present knowledge about men in my position.
I think you may have some time to celebrate a bit of good luck, no?
I wish you all the very best,
Patrick Turner.
Good to hear from you Patrick-Turner:
I’ve read a few studies that posit that people with DNA repair defects (brca and others) can get a better response from radiation. This sounds like he case with you ?!
LU177 is on the radar, especially now that we know he has multiple repair defects.
As always thank you for your comprehensive post— these posts will help people long after we all depart which is incredible to me.
Hi Dachshundlove,
When I was diagnosed in 2009, Psa was 6 and I had Gleason score 9, and 9/9 positive biopsy samples, young man's lethal and aggressive Pca. This was on Christmas Eve. Nothing could be done immediately, and wasn't done until 4 months later with Psa at 8, after all the docs have has holidays and gone to conferences in expensive posh hotels funded by drug companies.
I had lots of Pca but a fairly low Psa, and it turned out to be inoperable when doc opened me up for an RP, so I was scheduled for 2 years ADT and ADT 8 months later when ADT shrunk the PG size from 3 times normal volume with Pca outside capsule, and very probable mets spread widely. After 2 years, I quit ADT, Psa went from nadir of 0.08 to 8+ in 6 months, so back to square one. Then I searched for efficacy of 70grey of EBRT, very standard generic treatment and for Gleason 9 I had only a 10% chance of it working to kill Pca surrounding and within PG. So I assumed I was radiation resistant something more often discussed then than now.
Well, I had a good run from ADT which I had to re-start in 2013, then cosadex, then zytiga, but chemo failed. So then I had Lu177 and this has been the only agent to really get right in, roll up sleeves, and shoot up the Pca with alpha particles.
But now at Peter Mac in Melbourne, they are trialling Lu177 as primary treatment, and its called a lutectomy. Most other things like ADT et all can be used after if needed. This wasn't around in 2009, but would have done me a lot of good, and caused less side effects that I have had from EBRT and some added IMRT in 2016, and some added EBRT to right hip area last July. The Lu177 brought Psa from 25 before to 1.7 after 3 shots, then Xtandi was added to supercharge effect of No 4 Lu177, and 3 weeks ago Psa was 0.4, and PsMa scan report tells docs I have had a remarkably good response.
But this is not what happens with many fellows even though PsMa scans before Lu177 show it should work and often these men have mets that cannot uptake Lu177, so they grow and then the treatment becomes guesswork, experimental, with low rates of success. Docs are not saying I have any mets that have mutated and don't uptake Lu177.
So despite a few aches and pains here and there because I am 72, with some arthritis, I managed 42km this arvo on the bike and I felt very well.
So X-ray radiation used in EBRT, IMRT didn't do much, but ionising Alpha particles did a lot, so every man's sensitivity to different types of radiation vary. I had a guy tell me he had all my exact same primary treatment with 2 years ADT and EBRT, and Psa has gone to undetectable, been like that for 9 years. He said I'd be fine, but I just smiled and said "maybe" because I knew he'd had no cause to read up the scholarly articles online about what is likely depending on Gleason scores for EBRT.
Docs have mentioned I have Brca2 testing, maybe use PARP if I am positive, and I bet I am with strong cancer family history in females.
But it won't happen unless Psa whooshes upward, and PsMa scan shows mets that don't have Ga68 affinity, hence no Lu177 affinity.
My dear, the only certainty I know is that life is uncertain. Its 99% certain I will not get married. I've handled most challenges to my existence so far - without needing anyone to share these with; I met many who ran away from situations that required some real zeal and perseverance. I was thus forced to be strong, but really, I am but just a bloke, and all people have limited strengths to over come all things.
I've lived long enough to be sure that I know so little about so many things,
but I think I survived maybe better than about 6 billion other ppl who may possibly be a lot unhappier than I am. So I should be grateful that Nature has been kind; She is not easy to figure out, tends to practice tough love to humans, but when I am out on bike gliding along under blue sky by open fields and woods, and beside the lake's edge and seeing the birds doing their spring thing, and most humans being nice, it seems that life is good.
I do wish the very best of luck for you and your man.
Patrick Turner.
My dad is also somatic BRCA2 positive, he was diagnosed end of July this year with PSA 39 and 3 bone mets in the pelvic area. He has been on ADT +ZYTIGA since and it's been working very well for him. His PSA dropped to 0.7 the first month and to 0.2 on the second month. We'll see how long this will last. He receives treatment in China. If zityga fails we will consider olaparib. We can get it from India for a fraction of the price. Good luck to your husband!
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