I am wondering about studies where you only take one drug at a time to stretch out survival. In no order but for example Xtandi till it stops then ADT till it quits working then Zytiga etc.
Would this not give you extra survival? Is the above sequencing. Does combining hurt Monotherapy effective time.
If you start with casodex then switch to Xtandi does the prior casodex affect the Xtandi.
The thought is let’s say Xtandi gives you 3 years by itself then ADT is that better then combining the two. Thanks
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Canuck53
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The multipronged one won’t open for me but I found one you and Tall Allen participated in “is it necessary to continue on Lupron when you are on Zytiga ... good stuff.
Thank you, all of those are taking ADT my question is no combination one at a time, I couldn’t find anything. Hold ADT till every thing has failed. Secondly does Xtandi work after Casodex.
Xtandi (enzalutamide) should work after casodex (bicalutamide). There isn't any known cross resistance. There is cross resistance between enzalutamide and abiraterone. If you take one the other will likely be less effective after.
In my personal experience, after 15 months of successful Xtandi monotherapy finally failing(PSA from 374/to 3),,, ADT and chemo,,,Taxotere and Cabazitaxel all immediately failing,,,on my own tried Casodex monotherapy of 150 mg daily,,, spectacular 3 month result. Took 5 week PSADT to an actual 80 percent decrease in within 2 months. Then began rising again.
I'm obviously not following. They all tested a combination versus taking ADT monotherapy (no combination). In all cases, the combination increased survival compared to a monotherapy. There was a small trial of Zytiga monotherapy vs Zytiga+ADT that found the monotherapy suppressed testosterone equally well, but of course, that doesn't show it increases survival equally well. Maintaining testosterone suppression is the mainstay of all PC therapy - why would you not want to do that?
I have read where Xtandi works by Monotherapy in some cases for many years. We know ADT works as a Monotherapy I would say on average 2-3 years. All the rest do as well and they are using others developed in the last while.
So what I am asking is there any study that looked at taking one at a time, my thought is combining them works but do you lose time that taking two at once works against you.
I am on Zoladex for 6 months took it for 3 months in 2013, 3 months in 2015 I can’t climb stairs, I can’t squeeze, I have lost 80 to 90% strength on nov 20 th I am going in to ask to go on Xtandi alone to see if I can gain strength, because of cost I think they will agree to Bicalutimide (casodex) I cant afford to lose anymore strength.
Apparently you are referencing the relatively small European Xtandi monotherapy trial which did show quite good to excellent outcome for many. I first read of this some 3 years ago. As mentioned before,,,worked well for me for 15 or 16 months before slow failure set in.
Many forget or ignore the body slam to critical body systems and impact on OS(the list is extensive) and QOL that ADT engenders for many. If FDA submitted today, wonder if it would be approved,,,not that surgery solution requires approval.
Some have been on Casodex and other first generation anti-androgen monotherapies for very long periods and done extremely well,,,with very little of the downside(bigger boobs perhaps, excepted) of testosterone suppression.
Of course the question remains,,,would many have done as well,,,or better,,,with no systemic therapy at all?
Dr. Myers has a vlog post where he claims that no cancer has been effectively managed via monotherapy. Generally, at least 3 drugs are required.
He used a crude mathematical example. If 3 drugs each have a 1/10 chance of failure within x months, the combo will have a 1/1000 chance of failure in the same time frame. The odds for failure are additive for sequential treatment, but multiplicative for the combo.
It isn't entirely convincing, but, as someone diagnosed at 56 & knowing that Lupron would fail within 18-24 months (unless I was very lucky), I wasn't impressed by the monotherapy approach. 15 years ago, my combo option would have been Lupron+Casodex. I would then have proceded to Taxotere within a few years & not be writing this.
The combos that have been mentioned so far have the weakness that they target the same thing - the androgen receptor [AR] axis. Abiraterone targets the production of all androgens (not just gonadal), thus removing AR ligands, so one shouldn't expect much benefit from adding enzalutamide (which targets AR directly), if Abi is performing well.
A meaningful combo, IMO, might be Abi & two other drugs that target different pathways unrelated to the AR axis.
I (& many others) believe that debulking via cytoreductive prostatectomy may have a significant impact on survival, but it remains to be demonstrated. Debulking is not a controversial topic in some other cancer types.
Here's a paper from last week [1]:
"PURPOSE OF REVIEW:
"Local treatment of the primary by either radical prostatectomy or radiation therapy is discussed controversially. The role of cytoreductive radical prostatectomy has been evaluated in few retrospective clinical studies but data of prospective randomized clinical phase-III trials are lacking. It is the purpose of this review to reflect the current knowledge on indication, functional and oncological outcomes of cytoreductive radical prostatectomy to objectively highlight what can be expected from this approach.
"RECENT FINDINGS:
Cytoreductive radical prostatectomy (cRP) is associated with a long overall survival of more than 7 years and it is associated with a clinical progression-free survival of more than 6 years. When compared with nonsurgical approaches it becomes evident that about one-third of the patients will develop symptomatic local progression within 3 years whereas none of the surgically treated patients will experience such symptoms. cRP is associated with a low rate of significant complications and good functional outcome in well selected patients which do not differ from the results of a radical prostatectomy in treatment-naïve patients.
"SUMMARY:
"Patients with low-volume/low-risk metastatic prostate cancer (mPCA), good response to neoadjuvant androgen deprivation therapy and a good Eastern Cooperative Onology Group performance status appear to be the best candidates for surgery. cRP might be an individualized treatment option in the multimodality management of mPCA. It is the purpose of the current to highlight the indication, surgical technique, treatment associated complications, functional and oncological outcome for cytoreductive radical prostatectomy."
& another, also from last week [2]:
"In the past decade, a revolution in the treatment of metastatic prostate cancer has occurred with the advent of novel hormonal agents and life-prolonging chemotherapy regimens in combination with standard androgen-deprivation therapy. Notwithstanding, the use of systemic therapy alone can result in a castrate-resistant state; therefore, increasing focus is being placed on the additional survival benefits that could potentially be achieved with local cytoreductive and/or metastasis-directed therapies. Local treatment of the primary tumour with the established modalities of radiotherapy and radical prostatectomy has been explored in this context, and the use of novel minimally invasive ablative therapies has been proposed. In addition, evidence of the potential clinical benefits of metastasis-directed therapy with ionizing radiation (primarily stereotactic ablative radiotherapy) is accumulating. Herein, we summarize the pathobiological rationale for local cytoreduction and the potentially systemic immunological responses to radiotherapy and ablative therapies in patients with metastatic prostate cancer. We also discuss the current evidence base for a cytoreductive strategy, including metastasis-directed therapy, in the current era of sequential multimodal therapy incorporating novel treatments. Finally, we outline further research questions relating to this complex and evolving treatment landscape."
This is what I did. I started with casodex when PSA started to rise after orchiectomy and radiation. Casodex worked for 5 years. I then tried DCA which worked for 3 years. Then drug trials with zytiga (3 1/2 years), then xtandi (3 1/2 years).
Every year on monotherapy gave medicine a chance to catch up.
Thanks everyone, because of 3 bone Mets (I had sabr done to them) they say 3-5 survival years never asked when the 3 years started from?
Magnus1964 your results are super, my mind is leaning to Monotherapy also because of strength loss on ADT and hope one works for years then try another.
Me too. I’m on estradiol patches only as a form of ADT, but I also take metformin, dutasteride, rosuvastatin, celecoxib and duloxetine and eat mostly plant based foods and exercise regularly. So it’s a holistic approach.
My husband was on Eligard (Lupron) for two years and suffered all of the side effects. His strength diminished by 80 %, muscle mass almost disappeared, he has osteopenia, and weight gain. He tried to stay active, but he seemed to go down hill regardless of what he did. Now with serious back pain, he can do even less.
I would consider his treatment to be monotherapy, and it worked to bring his PSA down from 275 to .008. But his QOL has suffered. His doctor isn't giving him another hormone shot, so we'll see if testosterone comes back and if there is any improvement.
I feel for you and your desire to get "yourself" back. It has been difficult watching my husband go through so many negative changes, but he is still here and I'm thankful for that.
Thanks, in reading I note most lose strength but I am like your husband severe, hard to close car door, exercising is a challenge, QOL is important I want off ADT for now and go on what allows some strength building. New Dr. Nov 20 I hope is he progressive. ( medical oncologist) radiation guy doesn’t prescribe Xtandi etc.
It's the Lupron. They gave it to me for 6 months and I refused anymore. I'm almost 9 years out now and would never do it again. I avoided CRPC by not doing Lupron more than 18 months.
I am interested in your dx as well. What was your gleason score? Any mets on dx? It is a very interesting combination you are using but wonder if it works with a high grade metastatic cancer.
I am a fan of combined drugs, not mono-therapy. I had my longest remission knocking my PSA down to 0.1 and staying there for 2 years combining 3 drugs under Dr Charles E Myers. I tried 2 of those same drugs a short time under a Kaiser oncologist and the mono-therapy approach FAILED IMMEDIATELY. My 3 drugs were ketoconazole, estrodiol patches, and leukine (all off-label use back in 2008, but now patches approved for PC and Keto had been replaced by Zytiga). The 2 tried alone mono-therapy and failed were the first 2. One of Myers arguments is with tough resistant infections that cannot be treated with 1 antibiotic mono-therapy. Takes 2 different antibiotics at the same time.
Textbook oncologists dont believe me when I tell them my experience. Combined therapy worked better for me. I am sure there are trials showing the other drugs.
Met with MO he did not oppose the idea of Xtandi Monotherapy but the government medical system only allows Xtandi if you are resistant to ADT.
He is going to ask the drug manufacturer if they will supply it. They also apparently don’t like to prescribe Zytiga after Xtandi or Vice Versa which hurts my sequencing concept.
My point to him is I can handle the side effects of Zoladex except for the total loss of strength, I asked can we appeal to BC Cancer based on my feeing ADT is crippling me, answer no. Just to double check he is sending me to a rheumatoid specialist, wish I did this 6 years ago when 3 months ADT started crippling me. He thinks it was very unusual to lose as much as I did on just a limited amount of ADT.
He was not overly positive that Monotherapy on casodex/Xtandi would help that much with strength.
Well I am not pleased with it I appreciate the other guys who posted here about their terrible strength loss.
Last word I said on average you give me 3-5 years to live what do I have to lose with Monotherapy.
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A month of Casodex monotherapy
Xtandi monotherapy is very effective
Xtandi Monotherapy = To Lupron or Castration
