So, ADT2: Leuprolide (Lupron, Eligard) and Abiraterone (Zytiga) for example, is typical combination for mHSPC patients.
Although, the CHAARTED trial has determined - adding Docetaxel to ADT2 improves overall survival and prolong time to castrate resistance. A while back, I've posted adding Docetaxel to my treatment of Lupron and Zytiga, it seemed like a novel idea to many, is this mainstream nowadays?
Have not heard much about this here lately, an excerpt from the link below:
"In CHAARTED, the upfront addition of docetaxel to ADT also significantly improved every other secondary endpoint of relevance to patients. For example, combination therapy doubled the proportion of patients with undetectable PSA, a powerful predictor of long-term survival.3 Furthermore, undetectable PSA was maintained at 12 months twice as often in the docetaxel + ADT group compared with the ADT-only group. Docetaxel also significantly prolonged median time to CRPC (20.7 vs. 14.7 months; P < .0001) (HR for death, 0.56; 95% CI, 0.44 to 0.70) and median time to symptomatic or radiologic progression (32.7 vs. 19.8 months; P < .0001) (HR, 0.49; 95% CI, 0.37 to 0.65).3"
Neither CHAARTED nor STAMPEDE allowed the use of an advanced hormonal therapy (Zytiga, Xtandi, etc.) in the treatment or control group (the trials were completed before they became available for mHSPC) when they tested docetaxel+ADT vs ADT-alone. There is no evidence that combining docetaxel and an advanced hormonal therapy confers any advantage for mHSPC patients, and it certainly adds side effects. (The link you provided has nothing to do with this, so I'm somewhat confused by what you are asking)
The ARASENS clinical trial is testing the combination of Nubiqa+docetaxel+ADT vs docetaxel+ADT. It has finished recruiting, and results are expected in 2022:
Correction, should have defined ADT2, as version 2 for this prose, the CHAARTED quote has ADT. Because ADT2 is normally used as combination androgen therapy treatments.
As I wrote: "Although, the CHAARTED trial has determined - adding Docetaxel to ADT2 improves overall survival and prolong time to castrate resistance...', ,which is not incorrect to use "ADT2".
So, Zytiga was not in trial, my question, is there an ADT version 2 trial mainstream, because I've taken this treatment?
So you asking about a GnRH agonist/antagonist (like Lupron or Firmagon) paired with a first generation antiandrogen (bicalutamide, nilutamide or flutamide)? Those anti-androgens add very little compared to the more powerful hormonal agents and are usually only given to prevent flare in men with metastases. In CHAARTED, anti-androgen therapy was only allowed ≤ 7 days before castration to prevent flare. In the STAMPEDE docetaxel trial, oral anti-androgens were not allowed for the metastatic men.
I started with an antiandrogen only for about a few weeks, specifically Bicalutamide (Casodex); then started Lupron and soon afterwards added Zytiga/Prednisone, Bicalutamide was stopped.
Before taking Bicalutamide, had blood in urine and sperm, with a burning sensation when urinating. In just less than a week taking Bicalutamide, my symptoms improved 100%. So, the effect was much more than a flare abatement, at prognosis, PSA 1000+ with significant pelvic and spine metastasis.
Because at prognosis, with an "initial" large tumor burden, we decided to add Docetaxel. The CHAARTED and STAMPEDE trials did not report, Docetaxel and ADT as an adverse event.
TA, I guess I’m misunderstanding something. Above you state, “There is no evidence that combining docetaxel and an advanced hormonal therapy confers any advantage for mHSPC patients”. Doesn’t that contradict the Peace-1 trial results you just posted for us?
My journey as mHSPC is Casodex (briefly) before starting ADT + Docetaxel + Zometa (on the same day - not fun ). At the end of Docetaxel I continued ADT + Zometa and added Zytiga once I felt good enough post Docetaxel (2 months post Docetaxel). 8 Months later I had an RP + 26 lymph nodes removed (4 showed old signs of cancer). I am continuing with ADT + Zometa + Zytiga. A total of 3 years on this path and have been undetectable for 18 months.
I'm undetectable too @ PSA <0.02, almost a year at this state. Very interesting, you started concurrent Docetaxel at the onset, as just taking ADT + Zometa - docs like to stay in this SOC lane.
Then you had an RP after 8 months afterwards, why, when metastatic, very interesting, indeed...
Although no clinical studies to prove the efficacy, I did chemo, lupron and zytega plus SBRT to my three mets. Hit it hard and early was my choice and my MO’s recommendation. Of course he was using zytega early with adt long before the stampede trial showed it reduced deaths by 40%.
This is what I'm seeking, what was the rationale to use chemo early on with obviously ADT version 2, that is, adding Zytiga?
Having three mets is considered low tumor burden, so adding chemo was beyond SOC. I'm in the same mindset, "Hit it hard and early", but the stigma with chemo may be an "old wives' tale"...
Well to simplify it, here was both mine and my MO’s thinking. When the fire is in a waste basket it’s easy to extinguish. When it becomes a forest fire, not so much. And if A + B (adt and early zytega) is proven better than A or B alone, and if B + C (adt plus early chemo) Is proven better than B or C alone, than shouldn’t A + B+ C be even better ? Virtually every successful PC treatment has been shown in clinical trials to be more effective when given earlier. Logic seems to dictate all three are better. I went to ucla to get a second opinion from a well known MO. She said my logic sounded good and made sense and she’d love to see a Clinical trial in it. But until then she could not recommend. That’s the same reasoning many people are dying of covid 19 because drs won’t try one of these promising treatments until its proven in a clinical trial. My wife had an aggressive breast cancer 16 years ago. SOC was chemo. Her MO was also an out of the box thinker. He saw people with much more advanced breast cancer responding to a new drug called Herceptin. He said we should try it now before my wife’s cancer spread too far. We did it and she’s alive today. 7 years later a clinical trial on Herceptin showed it reduced recurrence 60% for her type of cancer. I’m convinced she’d be dead if she didn’t use the non proven Herceptin. Your call my friend. I may be wrong but, win or lose, I did what I thought best. My MO has seen great results with all three.
Congratulations on your wife’s’ results and especially for her life! That is why I am always looking for what is currently beyond the box called “SOC”. This despite my recent post saying that at least it is a good foundation against poorly considered ideas.
As with most things n life, we all need to gather all the available information and try to make an informed decision balancing the perceived risk/reward. There are no perfectly right answers. But with the new information the big 3 for PC and early herceptin for breast cancer, appeared pretty close to perfect. Thx for the kind words.
When I had my RP in 2016, there was much excitement about the use of Docetaxel + Lupron, which was the treatment course that I underwent. After stopping Lupron treatment, following a six-month cycle, my PSA began going up again. At seven months after stopping, I was considered BCR. I now have a tumor near my bladder and had SBRT for a lesions on my left femur (successful) that I found using Axumin scan while I was off Lupron.
At any rate, I am now on abiraterone + Eligard and I consider the Docetaxel a mistake. Had I been on only Lupron without Docetaxel, believe I would have had the same results without neuropathy in my legs and other negative permanent side effects from the chemo.
Abiraterone with Eligard has worked well for me since then in keeping my PSA at .05. I don't recommend Docetaxel early in treatment unless a higher tumor load warrants it. This seems to be borne out by subsequent studies which supported that approach and called into question the value of chemo for N1 localized spread post-RP.
If there's one thing I've learn about PCa, from my experience and sharing information here, is that our cancer cells are like a fingerprint. For instance, when diagnosed (PSA 1000+), I had numerous large tumors, invading the bladder, was miserable with pain and urinating blood. My scans showed a barrage of tumors, too numerous to count. Although, no evidence of visceral tumors...
But, with just Casodex for less than a week, no more symptoms, the new scans revealed total necrosis, no evidence of tumors. Eventually followed up with Lupron and Zytiga, holding at PSA <0.02 to date.
My point, obviously my PCa is extremely hormone sensitive, even at PSA <0.02, we decided to add Docetaxel, for a pre-emptive strike, circulating tumor cells (CTC) eventually mutate, if not, then metastasis would be curable.
You had an unfortunate adverse reaction to Docetaxel, fighting cancer is beyond brutal...
I had Docetaxel per CHAARTED back in 20015 to treat my G9 stage 4 hormone sensitive prostate cancer. I also started Xtandi while I was hormone sensitive in 2015 when I was a patient of Snuffy Myers. I’ve also been taking Avodart during that time per Snuffy.
My PSA has been undetectable since 2015, I had a recent blip when it was became barely detectable rwhen I stopped taking Xtandi at the recommendation of Dr. Sartor, we tried discontinuing it to help with some BP side effects I was experiencing. After the minor blip I resumed taking Xtandi and PSA is headed back in the right direction.
I was resistant to the idea of chemo at first but was convinced after reading the data from CHAARTED to proceed with it. It definitely wasn’t easy and there are lasting SE’s but hopefully it helped my current PSA track record. All part of the multi dimensional approach prescribed by Snuffy Myers.
So, diagnosed in Jan 14, surgery in Mar 14, T2CNoMx, GS 8, ECE, SV and margins negative, 10% prostate involvement. Surgeon says great pathology report, I won't have any problems....me, I don't like that Mx!
18 months later, PSA comes in at .2, then 90 days later .3. We start SRT in Mar 16, that is an epic failure when 90 days after 39 IMRT and 70.2 Gya, PSA is .7 then 30 days later 1.0...
With PSADT and PSAV climbing fast a trip to Mayo in Jan 17 for C11 Choline scan shows four PLNs but no bone or organ involvement.
I had discussed with my medical team here in Kansas City about using a combined therapy of ADT, docataxel and radiation based on the CHAARTED and STAMPEDE studies, their answer, you don't fit the profile so ADT is the SOC.
I said I may not fit it now but given my clinical history, GS8, 18 months to BCR, PSADT and PSAV I will be there soon. Mayo, Dr. Kwon put me on 24 months of ADT, six cycles of taxotere and 25 more radiation treatments which I started immediately. My medical team here in Kansas City was willing to execute the treatment and I would go back to Mayo for subsequent C11 Choline scans and consults.
With the first 3 month ADT and taxotere PSA dropped from 4.8 to .8, with the 2nd one, <.1, T to <7. Both stayed there. Dr. Kwon discussed adding Zytiga but based on my response, decided not to. We stopped Lupron at 18 months vice 24 given my response and emerging studies.
Last Lupron was May 18, by Oct 18 T was at 135, by Feb `9 it was 482. PSA has remained undetectable, last test in Jan 20 was .07. Next labs are 4 May.
This path was best for me, I chose it, it was aggressive but so was my PCA, not the SOC using NCCN guidelines. I had gone for the cure twice, surgery and SRT, both failed. Is this a cure, who know but certainly it has moved the PFS down the road, who knows about OS but I believe it has moved that too since given my clinical data I believe I was headed for an outcome that would not be good.
I feel like I am in AS now, my urologist and I test and consult every four months. We have an idea of what we'll do when it comes back, get multiple readings to gauge PSADT and PSAV, image using C11 Choline, Aximun or PMSA, then informed by that clinical data, make a decision on treatment.
Final note, when Kwon decided not to add Zytiga early on I vehemently disagreed, he may have been right. The complexity of this PCa and the myriad of treatment decisions, NCCN guidelines, SOC make this a very personalized decision for each of us. One of the changes I made which has helped was to quit thinking in 10-15-20 years windows (I was 57 when I was diagnosed, excellent physical health...). Instead, I ask my medical team if this can push the PFS 3-5 years, if so, great because we can treat again with newer regimens. This is of course, the whack a mole plan. I also liked Kwon's philosophy which was why do linear and progressive treatments with single agents when each was destined to fail. Why not combine and bring treatments forward to overwhelm the PCa early in its lifecycle.
I was diagnosed in October 2018 with a PSA of 216. Got a shot of Eligard only at that time. PSA and symptoms spiked, ouch, but then PSA plummeted. Had 5 radiation treatments to a vertebra. By early December PSA was down to 2 when I started docetaxel. PSA continued to drop and now ALP was plummeting too. PSA leveled out at 0.02 after chemo, then went to <0.01 after starting generic Zytiga and has stayed there. Long story short: each treatment seems to have made a measurable improvement for me.
BUT... 2020 started out with a diagnosis of neuroendocrine prostate cancer. Was this treatment emergent or did it develop alongside my original cancer? My MO says the latter, but it's not really important. I'm being treated for two different cancers at the same time, with chemo and immunotherapy for the NEPCa while continuing Lupron, Abiraterone, and Xgeva. My original biopsy indicated intraductal carcinoma, so my disease was rare and aggressive from day one.
There is also the PEACE-1 trial looking at both early chemo and early Abiraterone, but no results yet and probably not for years.
Well it took only one more year after your post and thread for the PEACE-1 results to come out this week and validate the enormous survival advantages of adding docetaxel to ADT plus abiraterone. Very good news for intensified treatment 👍
I know, actually suggested it to my Dana-Farber MO, Dr Mark Pomerantz, he agreed right away - even though PSA <0.02, didn't expect getting the order. He knew I did my homework, in short time was speaking the PCa lingo, "Hey doc, metastasis, darn all these CTCs flowing around, do we know if some are brewing AR-V7, or if any micro-tumors are anchored somewhere?".
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enzalutamide (XTANDI®, Astellas Pharma Inc.) for patients with metastatic castration-sensitive prostate cancer (mCSPC). 
