My Jevtana/Carboplatin results to date. Plus participation in Bipolar Androgen Therapy testing

[Mount_Rainier]

This is from my previous post which is much more detailed if you’re interested. I’ll pick up where that left off.

[“Jan 2022 PSA was 497.55 Alkaline Phosphatase was 92 after 4 infusions of Cabazataxcel.

After seeing the results of my last CT scan done on Jan. 2022, my Oncologists told me she had sent a referral to Seattle Cancer Care Alliance for a second opinion. She indicated the lung nodules had increased and that the chemo treatment was not working. She indicated it was going to take longer than normal to get a response from SCCA due to Covid challenges. She offered a drug called Carbozanitib, one pill daily indicating only a 30% efficacy.

I asked about adding carboplatin to the current chemotherapy (cabazitaxel) and she agreed to add it. She didn’t seem positive but more accommodating to my suggestion. She cautioned about continuing Chemo stating that if a Clinical Trial was available through Seatle Cancer Care Alliance, they usually want a 30-day absence from chemo treatment.

My question to my oncologist, regarding adding carboplatin to cabazitaxel was just that, a question to her, not a suggestion, as I had read of it being an option for others on this forum. She didn’t offer it up as a suggestion but indicated if I wanted it, she would agree.”]

The new post starts here:👀

Jan. 17 2022 PSA was 497.55

Feb. 7 2022 PSA was 1099.77. This was after fifteen months of steady increase off a low of 4.17.

My oncologist of 20 months ordered 2 rounds of CabazItaxel (JEVTANA) 39 mg Carboplatin (PARAPLATIN) 450 mg

Two days prior to a scheduled appointment with my oncologist, prior to my first scheduled infusion of the two drugs, I received a call from her office notifying me she was no longer part of Vally Medical Center where I had seen her from the day of diagnosis. No indication of her whereabouts was offered upon request. Because I had a pending appointment, my care had been handed off to another oncologist within the same clinic.

My wife and I met with the new oncologist and it was a substantive meeting that covered some of the issues at hand. Not a lot of recaps from the past 20 months. He knew that I had been referred to Seattle Cancer Care Alliance and that I was able to get an appointment with Dr. Robert B. Montgomery, known for being a prostate cancer specialist and having been active in new treatments and thinking outside of the box.

My new oncologist indicated he would have ordered the Jevtana/Carbo package also for my next treatment. He was a bit surprised when we told him, based on the wonderful contributions from this forum by those who have offered valuable insight on the subject, the combo was pretty much our idea.

Feb. 7 2022 I had my first Jevtana/Carbo infusion. PSA at that time again was 1099.77. All went well except for some intense side effects during the first week after the infusion.

Feb. 14 (seven days later) Blood work showed my first PSA reduction in 1.5 years. 896.25!

Feb. 23 I had my visit with Dr. Mongomery. He had reviewed my entire file and looked at all the scan results. He knew every bit of treatment and results from time of diagnosis. He said the Jevtana/Carbo combo is what he would have ordered. He indicated that my new oncologist told him when they spoke prior to our appointment that I had suggested the combo be tried. He also asked the source of my awareness and I gave full credit to those on the forum for their contributions. I hope you’re reading this and know who you are. Thank you!

Feb 23 continued: These are notes by Dr. Montgomery after our visit. ASSESSMENT AND PLAN - Patient is a gentleman with metastatic resistant prostate cancer who appears to be having at least a biochemical response to the combination of cabazitaxel and carboplatin. We reviewed that this combination is not necessarily considered a standard of care but has been studied in a number of settings, most extensively at MD Anderson for the treatment of what has been termed anaplastic carcinoma. It is notable that he has experienced significant toxicity with the first cycle and we discussed that we did run a clinical trial several years ago using a combination of docetaxel and carboplatin and that we have used that combination fairly extensively in patients once they have exhausted standard of care options. In our experience, some measures which can sometimes ameliorate toxicity are the prophylactic use of a drug used under the brand names Neupogen, Zarxio, and Nivestym to treat neutropenia (a lower-than-normal number of white blood cells), to prevent infection, (G-CSF), extending the duration of dexamethasone medication for several days after the usual discontinuation on day +1 and more intensive antiemetic regimens. I also noted that cabazitaxel and docetaxel have not been compared head-to-head in combination with carboplatin and if the toxicities become limiting, I suspect that docetaxel may be slightly less toxic in combination with the carboplatin. We reviewed that past this regimen the use of medications such as mitoxantrone certainly are possible but the evidence for efficacy in this type of setting is quite limited. We reviewed that lutetium is still under review by the FDA and the timing for approval remains uncertain.

And then we discussed the following: I reviewed that one approach that could be taken at present is to see if there is the possibility of detecting any specific molecular alteration that was not picked up with the foundation testing. I reviewed that the University of Washington oncoplex assay has in our hands often detected alterations which other assays do not, specifically biallelic copy loss of any number of different genes. If for example biallelic loss of BRCA or one of the other DNA repair deficiency genes was detected it might provide him with other treatment options. I also noted that it does evaluate for signatures of homologous recombination deficiency even in the absence of defined genetic mutations or copy loss. This may be useful in considering additional DNA damaging agents. I recommended that he represent to the VA this Friday and that we would consent him for sequencing of his iliac node biopsy and draw of a peripheral blood sample for either CT DNA or normal tumor normal sequencing.

Again this forum rises to the top as its members have posted about this possible treatment which I believe to be Bipolar Androgen Therapy (BAT) The study will be conducted through the local VA hospital where Dr. Montgomery operates a clinic and the costs for the blood sampling will be picked up by the VA as I am a member of the VA Health Care System. Blood has been drawn and we are told this testing takes about 30 days for results.

Feb. 28 PSA had climbed back to 1007. 24. I say that’s a net reduction of 100 points. Still an improvement!

Feb. 28 I had my second combo infusion and am waiting for blood work to determine the results.

We're all in this together! Keep Going!

[Tall_Allen]

I'm so glad there was some improvement by adding carboplatin. There is a good correlation between taxane+carboplatin success and PARP inhibitor success. The additional testing on your LN met or cfDNA may point to PARP inhibitors. But even if it doesn't, a recent trial combining olaparib and abiraterone found it was successful independent of HRR status.

meetings.asco.org/abstracts...

Interestingly, there was a trial of PARP inhibitor with BAT:

30 heavily-pretreated men who were mCRPC and who have progressed on either Zytiga or Xtandi, received BAT and the PARP inhibitor olaparib. Half had DNA damage repair defects. This was hypothesized based on lab findings.

• ¾ had at least some PSA reduction

• 47% had a PSA reduction ≥ 50% (44% if 2 who dropped out for progression are added)

• 23% had a 12-wk PSA increase ≥50% (28% if 2 who dropped out for progression are added)

• Median progression-free survival was 14.8 months if they were mutation-free vs. 7.5 months if they had the defects.

• 2 patients had a complete PSA response

• 5 of 8 90+% responders were free of DNA damage repair defects

• 3 of 6 90+% progressors had DNA damage repair defects

• 5 patients had serious (grade ≥ 3) toxicity, including one death

This trial suggests that BAT + olaparib achieved good response regardless of DNA damage repair defect status. Excellent responders had mutations of the T53 gene or DNA repair genes.

[Tall_Allen in reply to Tall_Allen]

Also, thinking about it, it may be useful to do an IHC analysis if there is enough tissue in your lymph node. Ask for an IHC for these antigens:

AR (androgen receptor), PSA, PSMA, MSH2, MSH6, PD-L1,chromogranin A (CGA), neuron-specific enolase (NSE), synaptophysin (SYP), DLL-3, CD56, Somatostatin (SST)

Even if SCCA doesn't have the antibodies for all of those antigens, the Wang Lab at Duke may have the rest.

Because your PSA is high and they said your cancer is anaplastic, I suspect you have more than one type of prostate cancer going on. The IHC analysis may guide you to clinical trials that may treat both kinds.

[subliminaldood]

Wow! I will follow your progress with this as I am just starting on Cabazataxel and Carboplaten at SCCA. PSA before first infusion was 60... Jumped to 108 21 days later at second infusion. Doctor says not to worry about that just yet. But you know how that is.

I am BRCA2 and they did mention that the Carboplaten was added for this mutation. But apparently the PSA doesn't respond immediately??? I don't know. Everything else in the blood was looking ok, did have a little nausea on day 3 - 5. Otherwise just the usual fatigue and of course bone pain (managed.)

Best of luck sir!

[MechD]

I am having my third chemo infusion today of cabazitaxel 20mg/carboplatin 4.0 AUC plus prednisone 10mg orally daily plus Nuelasta shot for WBC count. Lupron shot every 6 months. Initially my MO recommended I receive only Taxotere (docetaxel) 55mg. Consults with two other Oncologists recommended adding carboplatin since I have BRCA2. Insurance wouldn’t approve the docetaxel/carboplatin and after a peer-to-peer review with my MO, the cabazitaxel/carboplatin/prednisone was approved. Before starting chemo in January, PSA was 55 ( risen from 4 last June). After first infusion, 15. After second 5.

I have had no nausea/vomiting or hair loss at this point and haven’t missed any days of work (computer, not physical). Fatigue is mild and tolerable at same level as when I was taking Olaparib.

I am counting my blessings and hope you have good results!

[j-o-h-n]

Keytruda for lungs - worked on my lung melanoma.....

Good Luck, Good Health and Good Humor.

j-o-h-n Thursday 03/10/2022 10:24 PM EST

[bean1008]

Reading your stories gives me confidence that I am on the right path in continuing my treatment at SCCA. Lupron/abi/pred have been my drugs of choice for 13 months and have been doing the trick. But I’m a sponge for learning what I need to know for possible changes down the road. Best wishes to all!

[Mount_Rainier in reply to bean1008]

Yes, for those of us in the Pacific Northwest, Seattle Cancer Care Alliance, and its affiliates are major players. I feel most fortunate in having been referred to them. On my initial inquiry, I was told the Dr. I wanted was not taking new patients except on a referral basis. Now that we have connected I'm at ease knowing I am benefiting from his vast experience and knowledge. Members of this forum have been dogmatic in suggesting we be our own best advocate. The folks at SCCA seem very open to patient input.

We're all in this together! Keep Going!