"We demonstrated that lower PSA at abiraterone initiation, longer primary ADT duration, no prior ketoconazole, no prior chemotherapy and longer chemotherapy duration were associated with a longer duration on abiraterone in univariate analysis. In multivariable analysis, duration of primary ADT (duration of abiraterone 9 versus 13 months for ⩽12 versus >12 months ...) and no use of prior chemotherapy (duration of abiraterone 16 versus 7 months for no versus yes prior chemotherapy ...) were associated with duration of abiraterone."
1Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
2Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Abstract
BACKGROUND:
Androgen receptor signaling remains important in castration-resistant prostate cancer (CRPC) as demonstrated by the efficacy of abiraterone acetate (henceforth abiraterone) in phase III trials. Given that heterogeneous patient responses are observed, we sought to identify clinical factors associated with duration of abiraterone.
METHODS:
We retrospectively identified patients with CRPC treated with abiraterone in our database. Patient characteristics and types and duration of prostate cancer (PC) therapies were analyzed. These parameters were analyzed with duration of abiraterone in univariate and multivariable analyses.
RESULTS:
We identified 161 patients who had received abiraterone. All had received primary androgen-deprivation therapy (ADT), 86% prior secondary hormone therapy (SHT) and 33% prior chemotherapy. The median duration of primary ADT was 23 months, duration of SHT (excluding abiraterone) was 17 months and duration of chemotherapy was 8 months. We demonstrated that lower PSA at abiraterone initiation, longer primary ADT duration, no prior ketoconazole, no prior chemotherapy and longer chemotherapy duration were associated with a longer duration on abiraterone in univariate analysis. In multivariable analysis, duration of primary ADT (duration of abiraterone 9 versus 13 months for ⩽12 versus >12 months, P=0.03) and no use of prior chemotherapy (duration of abiraterone 16 versus 7 months for no versus yes prior chemotherapy, P<0.01) were associated with duration of abiraterone.
CONCLUSIONS:
Several clinical parameters, including type and duration of prior therapy, are predictive of responsiveness to abiraterone. These parameters are logical and correlate with smaller disease burden or less exposure to PC therapies. This information can help physicians counsel patients about the potential durability of efficacy of abiraterone. Identifying predictive biomarkers that inform patient selection for therapy is critical to optimizing treatment outcomes.Prostate Cancer and Prostatic Diseases advance online publication, 9 August 2016; doi:10.1038/pcan.2016.31.
PMID: 27502737 DOI: 10.1038/pcan.2016.31
[PubMed - as supplied by publisher]
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pjoshea13
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b) one has not had a lot of different treatments, other than ADT, but,
c) if one has had radiation, more is better than less
The big thing here is that prior treatment (& resistance to that treatment) might result in faster resistance to Zytiga.
The problem as I see it is that Zytiga is a castration add-on. So the cancer might already have a work-around that limits the effectiveness of Zytiga.
Castration therapy is like a barn with a lot of doors. Lupron closes the big door. Zytiga closes another. Xtandi another. Why not close them all at the same time?
Dr Myers has said that if several drugs have efficacy, resistance will take a lot longer than if the drugs were to be used in sequence. But I suppose it's tempting to think that its better to keep drugs in reserve. Unfortunately, we aren't talking about drugs that fail in ten years or more. They fail relatively quickly.
If someone has failed Zytiga, they have a significance chance of quickly failing Xtandi. & vice versa. So why not take together? What's another $8,000 / month?
This is consistent with our story. Primary ADT for 6 months before failure concurrent with early docetaxel with PSA and radiologic progression. Failed secondary ADT (PSA only increased during 4.5 months of therapy), PSA 136 at Zytiga initiation 10 weeks ago. PSA now 186 and pain has increased over last month.
Seems a no-brainer that aggressive cancer which does not respond well to initial treatments, may not respond well to later treatments....
i am at this moment on prednisone and abiraterone acetate through the VA and wonder what the cost would be if i were getting treated in the open market ? i would appreciate imput
My husband just started zytiga - cost was $2900.00 for one months prescription plus taking radiation at the same time plus hormone shot every 3 months - prescription next month will be $500 & the next month another $500 - we were shocked
I'm on Zoladex and Abiraterone + prednisone. Started on them together 1 month after diagnosis with a PSA over 600 5 years ago. All free in the UK as we have the NHS.
Any civilised nation should have free health care from cradle to grave.
Abiraterone costs £2900 a month I believe in the UK, if the drug company could get away with charging that much for it. Apparently the deal here in the UK is that the drug company only charges that for the first 10 months, then they supply it FOC.
Sad really in that Cancer Research UK 'invented' the drug, with public charity donations from citizens of the U.K. They then sold the patent and receive royalties from the Pharma company, who set the price so high that the UK NHS couldn't afford it. Crazy.
I know only what I picked up in the last hour or so.
Many of the 56 hits on PubMed are concerned with identification of the condition. Nothing that I could see referred to how a proper diagnosis would affect therapy. I don't recall anyone who had your diagnosis.
[1] alpha-methyl acyl coenzyme-A racemase [AMACR]
The one thing that I picked up on was:
[1a] "alpha-methyl acyl coenzyme-A racemase staining was seen in 93% of cases, with the majority showing strong and diffuse staining"
AMACR is an enzyme associated with PCa aggression, & has been regarded as a target. I wondered if there were any AMACR inhibitors.
[1b] (2014 - Italy) "Trifluoroibuprofen inhibits α-methylacyl coenzyme A racemase (AMACR/P504S), reduces cancer cell proliferation and inhibits in vivo tumor growth in aggressive prostate cancer models."
I can't find anything on "Trifluoroibuprofen" or "Trifluoro ibuprofen". (Wikipedia says that AMACR is involved in ibuprofen metabolism.)
[1c] (2011 - Johns Hopkins)
"While validating the most potent inhibitors (ebselen and DMPMB ..."
[1d] Ebselen (Wikipedia)
"a synthetic organoselenium drug molecule with anti-inflammatory, anti-oxidant and cytoprotective activity. It acts as a mimic of glutathione peroxidase and can also react with peroxynitrite. It is being investigated as a possible treatment for reperfusion injury and stroke, hearing loss and tinnitus, and bipolar disorder.
"Additionally, ebselen may be effective against Clostridium difficile infections.
"Ebselen is a potent scavenger of hydrogen peroxide as well as hydroperoxides including membrane bound phospholipid and cholesterylester hydroperoxides. Several ebselen analogues have been shown to scavenge hydrogen peroxide in the presence of thiols."
...
Here are a few recent links plus [5] - which makes me wonder how many of the 39 would agree with your diagnosis [LOL].
[2] (Sep 2016 - U.S.) "Recent Advances". Full text. Disappointing.
[3] (2016 - Sweden / Australia)
"... histogenesis, biology and clinicopathological features"
As also stated in [1]: "The correct identification of DAC has implications for treatment as well as outcome." However:
[4] (2016 - Italy) Case study.
"The rarity of this tumour forced to base our knowledge on small case series or on individual case reports, and does not help to establish appropriate guidelines. Therefore, the diagnosis of this tumour masks clinical implications that are still not well-understood."
"PSA proved to be a poor marker while, on the contrary, PET-CT scan has proved to be particularly useful in the management of the disease progression."
[5] (2014 -U.S. / Canada / U.K. / Australia / Sweden / France / Germany / Switzerland / Spain / Italy / Brazil)
"The diagnosis of intraductal carcinoma (IDC) of the prostate remains subjective because 3 sets of diagnostic criteria are in use. An internet survey was compiled from 38 photomicrographs showing duct proliferations: 14 signed out as high-grade prostatic intraepithelial neoplasia (HGPIN), 17 IDC, and 7 invasive cribriform/ductal carcinoma. Each image was assessed for the presence of 9 histologic criteria ascribed to IDC. Thirty-nine respondents were asked to rate images as (1) benign/reactive, (2) HGPIN, (3) borderline between HGPIN and IDC, (4) IDC, or (5) invasive cribriform/ductal carcinoma. Intraclass correlation coefficient was 0.68. There was 70% overall agreement with HGPIN, 43% with IDC, and 73% with invasive carcinoma (P < .001, χ(2)). Respondents considered 19 (50%) of 38 cases as IDC candidates, of which 5 (26%) had a two-thirds consensus for IDC; two-thirds consensus for either borderline or IDC was reached in 9 (47%). Two-thirds consensus other than IDC was reached in the remaining 19 of 38 cases, with 15 supporting HGPIN and 4 supporting invasive carcinoma. Findings that differed across diagnostic categories were lumen-spanning neoplastic cells (P < .001), 2× benign duct diameters (P < .001), duct space contours (round, irregular, and branched) (P < .001), papillary growth (P = .048), dense cribriform or solid growth (both P = .023), and comedonecrosis (P = .015). When the 19 of 38 images that attained consensus for HGPIN or invasive carcinoma were removed from consideration, lack of IDC consensus was most often attributable to only loose cribriform growth (5/19), central nuclear maturation (5/19), or comedonecrosis (3/19). Of the 9 histologic criteria, only 1 retained significant correlation with a consensus diagnosis of IDC: the presence of solid areas (P = .038). One case that attained IDC consensus had less than 2× duct enlargement yet still had severe nuclear atypia and nucleomegaly. Six fold nuclear enlargement was not significant (P = .083), although no image had both 6× nuclei and papillary or loose cribriform growth: a combination postulated as sufficient criteria for IDC. Finally, 20.5% of respondents agreed that an isolated diagnosis of IDC on needle biopsy warrants definitive therapy, 20.5% disagreed, and 59.0% considered the decision to depend upon clinicopathologic variables. Although IDC diagnosis remains challenging, we propose these criteria: a lumen-spanning proliferation of neoplastic cells in preexisting ducts with a dense cribriform or partial solid growth pattern. Solid growth, in any part of the duct space, emerges as the most reproducible finding to rule in a diagnosis of IDC. Comedonecrosis is a rarer finding, but in most cases, it should rule in IDC. Duct space enlargement to greater than 2× the diameter of the largest, adjacent benign spaces is usually present in IDC, although there may be rare exceptions."
Patrick...I stay in contact with a patient of Dr. Myers......He failed RP and SRP....had scans that showed hot spots and had proton beam even to areas previously radiated. Proton beam failed with rising psa after 12 months. Myers had him on all the supplements plus celebrex... also, failed zytiga.
Myers now has him on xtandi, lupron, avodart, arimidex, and metformin...so far for 6 months psa <.01
I'm glad that Xtandi has shown benefit for this man after his cancer became Zytiga-resistant.
I have used Avodart, Arimidex, and Metformin for some years now, & so I don't find the list unusual, but I have a few comments.
Dr. Myers has criticized other doctors who assume that with castrate T, DHT will be minimal. It was not the case with Myers himself. From my perspective, DHT might be protective in the early stages of PCa, but not when the PSADT becomes short. With castrate T, there is the possibility of the cancer finding a back-door way of making DHT, not involving T. Very likely, Avodart would prevent that.
Dr. Myers is now a convert to Metformin at 2,000 mg / day. I think that men should be offered Metformin upon diagnosis, & it should certainly be standard when ADT is started (because of the inevitable metabolic syndrome.)
Arimidex, which I have been on for 8-9 years, looks strange in that list, since Myers has stated that estrogen plays no part in PCa. Of course, the man may have elevated estradiol [E2] - but that would be unusual while on Lupron. In fact, E2 can be too low while on Lupron, & Myers has spoken about low-dose E2 patches for bone health while on ADT. Do you know the rationale for Arimidex in this case?
I think that Dr. Myers will one day add the statin Livalo to Metformin & Avodart. He has spoken of it & presumably uses it when patients cannot control cholesterol levels. But VLDL rises with ADT & I'd think that many patients would need a statin. Blood lipids are actually almost irrelevant, since, with CRPC, PCa cells can make androgen from normal levels of cholesterol, & can even make the cholesterol if necessary. I'm surprised that Myers hasn't made the jump, as he did with Metformin. He has already decided on Livalo as a statin that will not contribute to diabetes while on ADT.
It's interesting that your guy is doing so well on such an ordinary list. I wish him well.
Patrick...his next visit with Myers is in October and I told him to ask about immunotherapy and arimidex and I will report back when I get more info. How often do you take arimidex and at what dose. Did you read the just completed study that found early use of ADT lengthens time to CRPC....waiting increases the odds the PCa will develop cells with the genetics to become castrate resistant.
Very interesting and well thought out comments . As with breast cancer I think there one day will be a greater classification of multiple sub types of pCa . My medical oncologist at Memorial Sloan Kettering believes in the sequential protocol of prescriptions . Diagnosed 1/13 with Stage IV M1b continuing with Lupron Injections with a course of 45 IMRT treatments 2015 , also utilizing a .025 mg estradiol patch ( shown to be beneficial when cancer is androgen deprivation sensitive ) with a slowly rising PSA where most recent PSA demonstrated a small decline . I'm amazed at the lacked of efficacious treatment regimes amongst the most prestigious university based institutions
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Statins: new study regarding time to CRPC
Is this PSA drop good enough? from around 600 to 80 in 3 month on Zytiga for CRPC.
Impact of Androgen-Deprivation Therapy on Self-Reported Cognitive Function in Men With Prostate Cancer
Antidepressant medication use and prostate cancer recurrence in men with depressive disorders. 
Radiotherapy in the Definitive Management of Oligometastatic Prostate Cancer
