Shortly to meet doc and have my single confirmed met zapped, I will bring up the merits of progressing to a total kitchen-sink approach, acting on the belief that aggressive therapy early is the best chance to beat an aggressive cancer.
At my current state of knowledge this means combining ADT (transdermal estrogen) with chemo (Jevtana or Docetaxel) as well as Carboplatin, plus second-line hormonal therapy perhaps Zytiga plus a PARP inhibitor since I have a BRCA2 mutation. Possibly low-dose Bicalutamid too.
I am prepared for severe side effects but if they become intolerable I will quit the drug believed to be causing these.
Any comments would be appreciated; I haven't noticed anybody taking so many drugs at the same time.
I was diagnosed last September with GS9, low PSA, intraductal. My cell free DNA, an imperfect marker for the progression of PC, has increased from 2 to 16 ng/ml over the last six months, despite external and internal brachy radiation and ADT Firmagon plus Bicalutamide.
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Because You have BRCA 2 mutation, an aggressive ,combined treatment regimen is rational approach. BRCA 2 mutation makes the prostate cancer aggressive and a multipronged attack is necessary in such case. Having High Gleason ,low PSA and Intraductal histology ..all are indicators of aggressive type of PCa. So go for total combat with your Doctors' help.
Thanks for the encouragement, LearnAll.I will add clioquinol and cabergoline to what I ask for from doc, as I read from you earlier about. . So it really becomes a total approach! If it is too weird for him, I may go for vitex despite some possible estrogen suppression effect (which may be the case for cabergoline too but less clear haven't found anything on it)
At one time, I was considering only adding clioquinol, zinc and some prolactin-inhibitor to the ADT. But. Costello says eight weeks to see the hoped for effect from cabergoline and given the aggressiveness of my cancer I don't dare delay the other new treatments that I plan to start next week.
We have different level of aggressiveness in our PCas but I am still using multiple supportive interventions to ensure longer term remission. Recently, the researchers have been publishing about SENOLYTIC use to delay progression. This is nothing but saying in a round about way that vegetables and fruits help . They came with this fancy name "Senolytics." So what are Senolytics ? These are vegetables and fruits which contain Quercetin, Fisetin and Longpiperines etc. These substances keep the prostate cells younger and thus, make them less likely to become cancerous or mutate.I have used Zinc chemotherapy for a year continuously . Stopped recently to give a break.
I had no side effects but it is difficult to know how much it helped because of multiple supportive things being done by me to keep PCa in remission. Most recent one is taking powder of Pygeum Africanum bark as research shows that it not only helps with BPH but also acts as Anti Androgen.
In a symbolic way, we can say "it is important to kill existing terrorists but it is more important to prevent the youngters to become terrorists. "
Thanks LearnAll I will start checking the substances you mention after I'vê done the treatment decision with doc. I will start looking at your profile and posts imagine I can find it there.
Adjuvant ADT has sufficient evidence to show that it makes the radiation results better (SBRT). Probably it impairs RT treated cells from recovering and increases their "death spiral" when they go to divide later. Duration is controversial but you probably should be on ADT anyway. Addition of Zytiga/abiraterone seems wise and will support this. But that leaves the bicalutamide unimportant with nothing additional to contribute.I would try to get Provenge in the immediate wake of the SBRT if you have not already had it.
As for the docetaxel/carboplatin chemo, I have doubts if it would be favorable to combine at the same time: It will impair cell division which is necessary for the efficacy of the SBRT. Consider and discuss if it should be delayed for 3-6 months or so?
The trouble with the "kitchen sink all at once" approach is that if you due have severe level SEs, then you don't know which part to discontinue or modify.
A PARP inhibitor certainly will have a place in your treatment. But whether now or later, and what to best combine it with will require more expert combing through clinical trial experience. Combo treatment trials are currently underway. I would look there and maybe consult with lead investigators.
The ASCO meetings next month will very likely have new information/results in this area.
I will bring up Provenge, there seems to be little downside to it.
With platinum-based therapy indicated for those with BRAC2 mutations, I would think Carboplatin could be used now without Docetaxel.
Reading up, evidence of what you suggest, Zytiga first before possible chemo, is strengthened by that sequence reportedly being superior with the BRCA2 mutation.
In addition, chemo seems to be inferior in the presence of intraductal cancer; but cannot grip whether this is valid in my case with only 2 out of 16 samples intraductal, and not the worst ones, and after metastasis has emerged.
You are still hormone-sensitive, right? The only medicines approved for you are ADT, chemo, Zytiga, Erleada, or Xtandi. You may be able to convince your insurance to cover the others. Good luck.
TA, With T ultra-low and with a sharply rising cfdna count, if that number is to be trusted, I suspect I have become castration resistant after just six months of Firmagon. With a BRCA2 mutation, that is supposed to happen much quicker.
If so, I suppose continued ADT is of no or limited help, is that correct? What about Zytiga, which I understand is an extended form of ADT.
Just one met was confirmed with my second PSMA PET/ CT, in my right iliac bone. If the cancer is progressing I suppose this means there are micrometastasis in the bones too small to be detected....?
For my meeting tomorrow with doc I will bring up radiopharmaceutivals as well. These, at least Xofigo, are indicated with the BRCA2 mutation. And there appear to be synergy effects with both immunotherapy and PARP inhibitors, which I will also bring up.
It is a mistake to think of castration resistance an event. one can't be half-pregnant, but one can be CR to a greater or lesser degree, and with different reasons. That said, your cancer was never very hormone-responsive, and PSA is a poor biomarker for you. You may have an anaplastic type. If so, Firmagon should be continued but second-line hormonals may be ineffective. If so, a combo chemotherapy with cabazitaxel+carboplatin may be a good next step.
Once there are metastases big enough to be detected, there are always thousands of micromets to small to be detected. This is why metastasis-directed-therapy is controversial.
cfDNA is problematic - is the DNA shed from living or dying cells? It may also be that your type of prostate cancer does not express much PSMA. An FDG PET/CT may be more informative. You may want to request that.
If any of your metastases are big enough, you might want to biopsy and do a cell histology, and IHC analysis (stain for AR, PSA, PSMA, PD-L1, CGA, synaptophysin, NSE, CD56, DLL-3). The best place to get this type of analysis is the Wang Lab at Duke.
A PS to what I just wrote, making it even longer....The synergy effects, that I believe I have read from your newsletters, are between Xofigo and immunotherapy and PARP inhibitors. However, at my clinic they are using Lutetium 177, which it has pioneered in my part of the world.
As for my suspicion of being castration resistant and questioning whether ADT and Zytiga are of use: "germ line DNA repair defects - which I have - attenuate response to AR-targeted therapies and make for poor response to standard hormonal treatments" according to one research paper.
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