I just thought I would update my latest progression, scan findings, and plan of care established. You can view my profile but in a nutshell went to a free screening in the fall of 2012 but they never contacted me until early 2013 where 12 core biopsy revealed Stage IV M1b with extensive lymph node and pelvic and spinal skeletal metastasis. Began with Firmagon loading dose then switched to Lupron. Had 45 IMRT radiation treatments in 2015. When PSA began to rise I was prescribed bicalutamide where my PSA began to once again rise after having been undetectable for several years and in March of 2021 placed on darolutamide. Once again PSA began a slow rise where it reached 2.18 in 10/22. A CT/PETPSMA scan was performed on 10/21 which revealed extensive retroperitoneal lymph node metastasis but with mild PSMA avidity SUV max of 2.1-4.7( Liver 7.1- Parotid gland 12.8). Follow up CT scan again revealed extensive lymph node involvement including Left supraclavicular nodes. Trans differentiation into neuroendocrine type was suspected but Chromogranin A was normal and supraclavicular node biopsy on 11/9 revealed adenocarcinoma after several IHC markers for neuroendocrine were negative. The biopsy tissue will also be used for MSK Impact clinical trial for extensive genetic testing of the cancer itself. At my latest MO visit ( with Dr Yu Chen at MSK)’ on 11/23 I was given several choices for next plan of care. I was f first offered chemotherapy with docetaxal which is the standard of care, go on Abiraterone acetate, or enzalutimide , or enroll in a clinical trial of an AR degrader C-94676 which is in phase1/2 where dose escalation has reportedly been completed. I did so also because I have done well with AR antagonists so why not take it a step further. I technically had to refuse the chemo option (as it is SOC) because I already have peripheral neuropathy and it will still be an option if the trial treatment fails. I didn’t chose abi or enza due to cross resistance concerns. I will begin the trial on 12/21 due to the necessity of a required washout period of 4 weeks of the darolutamide which has been discontinued. I also wanted to do the trial to help the many men diagnosed Stage IV, where hopefully the DNA mutations in the biology of my cancer can be matched to the success or not of AR degraders. I will keep the group, which I am so indebted to, informed along the process.
Edward
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wagscure259
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Not as yet and they may not in the near future. It will take about 30 days to complete the results, They will probably be more concerned with the DNA mutations that the AR degrader is effective for. For example preliminarily with ARV-110 another AR degrader they have identified DNA mutations AR T878 and H85 for efficacy.
So true. I am aware of that combination. I wonder what the side effect profile would look like combining docetaxal with enzalutimide. I did consider chemo then try a repurposing of the darolutamide or enza. As always TA Thanks for the info!
I would be reluctant to use docetaxel if you were to go with chemo at some point, due to your existing peripheral neuropathy. Cabazitaxel might be a better choice for you. But your current plan is sound. Best of luck (inherent variability of individual responses) with it.
. Clinical Use of Nuclear Factor-Erythroid 2 p45-Related Factor 2 and AKR Inhibitors to Surmount Chemotherapeutic Drug ResistanceThe ability of existing drugs to inhibit AKR1C isoforms selectively has been tested in some clinical trials. In the Nurses health cohort study, the use of both aspirin and nonaspirin based NSAIDs prolonged the survival of ovarian cancer patients where the primary chemotherapeutic agent was cis-platin and demonstrated the clinical utility of inhibiting an AKR1C isoform (Trabert et al., 2014). The clinically approved COX inhibitor INDO is currently in phase II clinical trials to surmount drug resistance to abiraterone acetate and enzalutamide mediated by AKR1C3 in castrate resistance prostate cancer (see NCT02849990 and NCT02935205). AKR1C3 has also been targeted in AML using a combination of 6-medroxyprogesterone acetate (a pan-AKR1C inhibitor) and bezafibrate (a PPARγagonist) with the goal of preventing PGD2conversion to 11β-PGF2α and preventing cellular proliferation (Murray et al., 2010); this approach has led to a phase II trial (Murray et al., 2019a). To move AKR inhibitors into oncologic practice to improve drug response to anticancer drugs, trials are in their infancy. Adaptive clinical trials that exploit overexpression of AKR isoforms could be considered so that personalized treatment based on tumor phenotype and AKR isoform specific inhibitors could be a treatment strategy
Surely an interesting concept where specific DNA mutations, and biology of one’s cancer would have to match the individual tumor phenotypes. May lead to a future treatment approach.
best of luck with the new treatments. Your updates are very helpful to us all. Do you mind sharing your numbers when your investigating the neuroendocrine canser? Your chromogranin A, etc. and what was the test that based on it, they decided it’s neuroendocrine pc? I am also been treated at MSK.
<93 ng/ml normal . Now this in and of itself does not rule out neuroendocrine. My needle biopsy of the Left supraclavicular node of the in part revealed tumor cells were positive difusely positive for NKX3.1, ( indicated adenocarcinoma) whereas PSAP is focally positive. Other stains such as DLL3, synaptophysin and others performed as well but I don’t have specific info related to those only that they were negative for neuroendocrine differentiation.
Although CgA is the most widely used tumor marker in patients with a suspected or confirmed neuroendocrine tumor, CgA testing has limitations.CgA levels can be elevated in a range of health conditions other than neuroendocrine tumors. For example, CgA levels may increase in people with irritable bowel disease, chronic hepatitis, liver failure, inflammatory diseases, and renal failure. Several medications can also cause an elevation in CgA levels.As a result, CgA testing for neuroendocrine tumors may produce an elevated result that shows signs of a NET when a person does not actually have this kind of tumor. Best to consult with your MO regarding your concerns!! Best to you
It certainly changes the plan of care , often can require a platinum based therapy, and if small cell type lifespan is certainly impacted especially with visceral invasions.
I assume CC-94676 and C-94676 are the same thing? If so, then I started it 4 weeks ago today. My quick history, diagnosed Oct of 18, PSA 43.6 12 of 12 biopsy cores positive Gleason 9, some 8. Firmagon, then Lupron every 6 months since. 28 sessions of radiation to my prostate and a spot near my prostate (Ischium I believe) Radiation to spots on ribs and one on the top of my back/neck all in the bones. Started Zytiga Nov. 2018 and switched to Xtandi after liver enzymes raised after 6 months (June 2019.) Officially undetectable from Sept. 2019 until June 2020. then.... .
.02 6/20
.04 7/20
.09 8/20
.33 11/20
1.05 1/21 Scans showed 1 spot near my tailbone. Had radiation to that spot.
.83 4/21
.39 6/21
.54 8/21
1.01 11/21
1.77 12/21 PSMA PET scan showed 6 spots, plan was radiation to 3 spots C1, and right femoral and pelvic area next to the femoral spot Then Provenge completed Feb. 2022.
PSA then went to
.25 3/22
1.01 7/22
2.23 10/22
3.07 end of Oct. while prepping for the clinical trial.
So far I've taken a break from knowing every detailed PSA result as I don't know if the anxiety from the anticipation has been worth knowing every reading. I've tolerated the drug well, just some sluggish feelings and slower resting heart rate. I'll have scans in 4 weeks and will see hopefully good results. I am thankfully still active.....turned 50 this past Feb. and still work full time, raising teenage twin boys and getting my daughter through college. I run a few miles every other day and lift weights. Mostly healthy vegan diet but not always. I'd say about 85% of what I eat is vegan. I was 100% for 3 years but after things started to progress I figured no need to deprive myself of the occasional shrimp and grits or fettuccini alfredo.
Yes it is indeed the same trial. I believe it was CC- 94676 when Celgene who developed it. owned it., now owned by Bristol Myers Squib. Oct18, it appears you are doing everything right. I know the drug can cause prolonged Q-T waves. That’s why we did an EKG baseline test at the beginning of the trial. Just make sure your resting heart rate doesn’t dip into the 40’s although mine has previously. It generally runs in the low 50’s. I have returned to my vegan diet only because I like how I feel on it. DONT deprive yourself of the pleasures of eating what you want occasionally. There’s certainly no curative diet for us but exercising and keep a good BMI may help with cardiovascular side effects of being castrate. BTW my PSA dipped below 2.00 ( a requirement to enter the study) probably due to darolutamide withdrawal so they just scheduled another PSA for 12/16. I just wanted to ask how many pills are you taking? Regards and my best to you.
My resting heart rate was in the upper 50's/lower 60's before the trail. Now it is about 10 beats lower, upper 40's/lower 50's. It still gets up when active, especially running and working out. They are keeping a close eye on it but tell me so far so good. I am taking 12 100 mg pills daily. 6 in the morning and 6 at night. And I definitely agree with feeling good on a healthy vegan diet. My BMI, digestive system, and overall health is good due in large part to diet and exercise.....except for the cancer obviously. I guess this can be the one time you won't be disappointed in a rise in the PSA so you can qualify for the trail.
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