Update on PARP inhibitors

[Hazard]

Background

2018 started off brightly. After 6 cycles of docetaxal PSA went from 47 to 1.8 (May 2018). But once the soft stuff was gone, PCa started progressing again and was back to 4.6 after Cycle 9 (June 2018). MO cancelled Cycle 10 and put me on Enzalutamide. 3 months later PSA had risen to 15.1 (Sep 2018, no impact at all on PSADT) so MO discontinued Enza.

I was then enrolled in PARP inhibitor trial (niraparib). While my germline DNA is clear of any bad mutations, my somatic DNA showed that BRCA2 gene had undergone bi-allele deletion - not mutated but completely missing. MO said that this made me a perfect candidate for PARP inhibitors and I should expect to get better results compared to most people on trial, who typically had a mutation in a single gene.

PARP Inhibitor Results

So I had bone scans, CT scans and PSA test to set my baseline (PSA still rising rapidly and now at 60 by early November). I have just had my 2 month check up (7 Jan 2018) with fresh scans and here are the results:

Bone Scan. At least 5 new osteoblastic foci relative to baseline scan.

CT Scan. Progressive hepatic metastatic disease. Progressive mesenteric and retroperitoneal lymphadenopathy. Progressive intraperitoneal disease. Increase in size of the mass at the prostate bed.

PSA. from 60 to 433 in 2 months.

During this period I have also had 3 hospital admissions.

- left hip effusuion and musculature edema requiring drainage and investigation, found to be caused by metastisis in the medial wall of the left hip joint.

- blocked bowel. Caused by metastastic lymph nodes pushing into the small bowel.

- Internal bleeding in Upper GI tract. Collapsed at home at had 2 litres of blood transfused upon arrival at emergency. This bleed resolved itself, surgeons believe it was due to combination of non-steroids (ibruprofen) used for hip pain, and steroids (dexamethsone 16mg perday) used to treat bowel inflammation following the blockage.

As MO said when reviewing my new scan results "This is bad disease". Niraparib was discontinued. She is most worried about my liver as CT scan showed "numerous hypodense lesions" the largest 29 x 22mm. So I had PSMA GA68 PET scan yesterday.

- if liver lesions are PSMA avid then I will start lutetium 177 ASAP.

- if liver lesions not avid, I will be back to chemo - this time she said it will be cabazitaxal plus carboplatin.

There are still options, no-one has called time yet nor offered a prognosis so let's keep fighting!!

[NPfisherman]

Keep fighting the beast, brother...Best of luck....

Fish

[MontyB]

Absolutely you are right...I am with you on this...keep fighting and now fight it with something else!

Take Care,

Monty

[j-o-h-n]

Kick your Pca to the curb...

Good Luck, Good Health and Good Humor.

j-o-h-n Saturday 01/19/2019 12:15 AM EST

[Hidden]

Sorry to hear how things have worked out. I have the BRAC2 mutation and trialed Olaparib. Didn’t work at all. But don’t give up - there are other options and I’m still going almost three years after that trial.

[HopingForTheBest1 in reply to Hidden]

I am also BRCA2 positive. So far I have not had any specific treatments for this, as I have been on Zytiga, Prednisone, Eligard and Xgeva for the past several months after initial diagnosis. I may need to consider sooner than later as I have had recent rise in PSA from 0.15 to 0.38. My MO has talked about me possibly going on to Olaparib, but I wondered about other more recent PARP inhibitors like Rucaparib, Talazoparib or others that are currently in trials. Would love to know how it is decided which one to use, and if the first one fails can another be used in its place. How long were you on Olaparib before stopping? What are you on since? Hope it is working for you now.

[Hidden in reply to HopingForTheBest1]

Around six months. If you look at the top of one of my posts there is a chart that will show you what happened to my psa. Good luck buddy.

[grahaminator63]

Keep up the fight! You’re in my prayers.

[Cmdrdata]

Hazard, I am praying for you that you will be in peace and have sustaining comfort from the Lord as you fight this disease. Appreciate your detailed info on what you are going through, as someday some of us may be at your stage. Thanks again.

[snoraste]

With proper treatment such as LU or AC, the metastasis will disappear as quickly as they showed up. Also consider combinationtherapy with PARP and a pdl1 inhibitor. Long road ahead. Keep fighting.

[Lombardi24]

You are a brave man.

[Stegosaurus37]

Your prePARP history sounds pretty close to mine. I also have the BRCA mutation and will be on the TRITON rucaparib trial starting this coming month, as soon as they've finished all the prelims. Your results hopefully won't be mine but I'll let the group know.

[Hazard in reply to Stegosaurus37]

Good luck with rucaparib. I sincerely hope that you get much better results.

[Stegosaurus37]

I do too!

[Bebby1]

Keep fighting matey

You are not alone

[monte1111]

If Tom Brady can do it. So can you. No replies from Tom Brady haters please. I only like him cause I like to see the look on the young people's faces after he does his magic.

[Grumpyswife]

Sir, You are one awesome fighter. Stay strong!

[Hazard]

Thanks to all my brothers who have sent messages of love and support. I am touched by all the comments.

So I saw the MO today. PET PSMA is lighting up lesions in bones and lymph nodes but liver lesions are demonstrating low avidity. MO says that we gotta target the liver and is recommending that we move onto chemo, if this cleans up liver then LU177 is still an option later on for the many avid bone and soft tissue mets.

But before we start chemo, MO wants to do a liver biopsy. She says that PCa is increasingly heterogenous, and with extensive liver disease there is a chance that it has developed neuroendicrine characteristics. In this case, we need to move to carboplatin + epotoside. If no neuroendicrine disease, we will start will start with cabazitaxal and add carboplatin if response is not too good.

The fight continues.

[George71]

I would call Dr. Bob Liebowitz he has gotten miraculous results.

compassionateoncology.org/v...