"Christopher Sweeney, MBBS, physician, Dana-Farber Cancer Institute, compares treatment with abiraterone acetate (Zytiga) verus docetaxel in patients with prostate cancer."
"Both drugs have their pros and cons, according to Sweeney. Abiraterone is an oral agent that must be taken for months at a time. While the side effects may not be as severe, they can be longer lasting than those seen with docetaxel. Adverse effects include high blood pressure and diabetes. Docetaxel, on the other hand, which is administered intravenously, only needs to be given to patients every 3 weeks for 6 cycles. However, the agent comes with typical chemotherapy-related toxicities, such as fatigue and weakness, low white blood cell counts and neutropenic fever.
Deciding between the 2 agents is often difficult for clinicians and their patients, especially since the two have nearly the same efficacy, according to Sweeney. Once a patient progresses or stops responding to one of the treatment, they will often be switched on to {the other}."
Regarding Zytiga, I have hypertension and I am a diabetic who has his diabetes under control without drugs, my A1C test is 5.8. So I say bring it on!
If I worry about everything, how am I going to enjoy life. I am enjoying life.
Rich
Thanks Patrick. One other consideration for some people might be the cost. The chemotherapy is less expensive which might be factor. Another thing to think about is the longer term when you will be using the other of the two treatments later on. From what I've heard, it looks like chemotherapy is less effective than Abiraterone if used later on, but I haven't seen any actual studies on that. Also there is the possibility of re-challenging whatever was used early on. So I'd also be wondering which would be more useful in that setting.
In my situation, I did the early Docetaxel before the results of the Abiraterone arm of the STAMPEDE trial were released. Now that I've completed chemo, I've had 3 doctors tell me not to do early Abiraterone in addition to early chemo.
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I don't know how to wrap your last statement around my head. For the study "you did this", and now you know, "DON'T EVER DO THIS!" I thought they were going that way with early combo treatments anyway. IDK
J
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I don't understand your post.
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You say you were on the Abiraterone leg of the study. I thought this to mean chemo and Zytiga. I got turned around with my drugs. All on me Gregg.
J
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I was not in the actual trial, but used the data from it to make my decision. At the time of my decision, only the CHAARTED and chemotherapy arm of STAMPEDE trials were published so I went with the early chemo. Half way through my chemo, the Zytiga arm of STAMPEDE and LATITUDE trial results were published. I asked 3 different doctors whether it was advisable after chemo to then additionally do the early Zytiga but all 3 said no. Mainly because there were no trials using both at the same time.
If there is an onslaught by hormone insensitive ( refractive ) PCa cells, can Abirateron counteract and stop them ? These cells have nothing to do with androgen or androgen related drugs or action. Docetaxel on the other hand is cytotoxic ( killing cells ) and are capable of destroying a wide spectrum of PCa cells ( hormone sensitive or insensitive ). How do you look at this situation? Combination of the two may be the meaningful answer unless one considers the side effects of chemo as disastrous.
Hormone refractory PCa [HRPC] is disease that is no longer helped by any form of hormonal therapy, whereas CRPC is disease that is progressing even though T is castrate. So my understanding is that to have HRPC, one must have CRPC & have failed abiraterone too.
(In the past, before the term CRPC was coined, HRPC was used, because those who failed ADT were thought to have androgen-independent disease, but mostly this is not the case.)
Exactly, I referred to the type HRPC ( Hormone Refractory ) disease. In other words androgen-independent disease. When you say "mostly this is not the case" do you mean to say it is a very rare occurrence ( HRPC disease )? Position is clear when you say "to have HRPC, one must have CRPC & have failed abiraterone too".
For some years I was reading that when Lupron failed, PCa no longer needed androgen. It seemed to come as a surprise to many researchers that the androgen receptor [AR] continued to be involved.
I remember feeling a bit uneasy when papers appeared saying that, clearly, there was nothing wrong with the ADT concept, but it hadn't been taken far enough. Where was this going to end? The elimination of all steroid hormones? What about the effect on the body?
Anyway, Abiraterone appeared & its creators must be disappointed that Abiraterone + Lupron, while a great improvement, doesn't really solve the ADT problem.
One form of resistance involves AR splice variants that do not need androgen. Is ARV-7 PCa HRPC? Perhaps not, since the AR is still involved. Xtandi & Casodex target the AR - not hormones - but it's all part of the same approach that Huggins initiated.
Thank you very much Patrick for your time and efforts to use a little bit of your vast knowledge to clear my doubts.In my understanding CRPC is a stage in the process of treatment with the androgen deprivation therapy ( first line or second line ) where the hormone sensitive PCa cells develop resistance to the treatment. But the case with HRPC is different. It is just there by virtue of the fact that PCa is heterogeneous. All the PCa cells don't depend on androgen and also don't produce PSA. Apparently our early treatment protocols/strategies don't seem to pay sufficient attention to deal with HRPC cells and eliminate them. I fail to understand the reason why? I also have a feeling when we spend all our time to destroy hormone sensitive PCa cells and spare the most dangerous HRPC cells, they will have more space and freedom to thrive! Since I don't have sufficient research experience, I have no idea as to whether my observation has any clinically significant value.
To stretch the definition, stem-like PCa cells are the ultimate HRPC cells, since they do not need androgen. Consequently, most of our treatments leave them unscathed.
Thank you very much Patrick. I don't think any better answer could be given. However, is there any known valid reason for the treatments to ignore the presence of the stem-like PCa cells .....HRPC cells and leave them unscathed?
Some have said that Nixon's "war on Cancer" failed because we knew nothing about "stemness" in cancer, & you wouldn't find them unless you were looking for progenitor cells, & then maybe not.
Those of us who jumped on Metformin, couldn't have anticipated a stem cell benefit [A]:
"The anti-diabetic drug metformin as a potential anti-tumor agent targeting CSC subpopulations
"Metformin, a biguanide, oral hypoglycemic agent, is the most commonly used drug for the treatment of type 2 diabetes mellitus (DM). Metformin reduces blood glucose levels by the down-regulation of hepatic gluconeogenesis and up-regulation of glucose uptake in peripheral tissues, such as skeletal muscle and fat (Shaw et al., 2005). It also enhances the insulin sensitivity of tissues, thereby reducing insulin levels overall.
"Epidemiological and clinical studies indicate a reduced incidence of breast and pancreatic cancers in DM patients taking metformin, and that its consumption improves the clinical outcome of cancer patients (Bowker et al., 2006;Heikkinen et al., 2007;Landman et al., 2010;Libby et al., 2009;Monami et al., 2009). While these findings suggest that metformin has anti-tumor effects, the mechanism of this action remains undefined. One possibility is that the metformin-induced increase in insulin sensitivity inhibit cancer cell growth by activation of AMP kinase (AMPK) which, in turn, inhibits the PI3K/Akt/mTOR signaling pathway via phosphorylation of mTOR (Dowling et al., 2007;Zakikhani et al., 2006) and a rapid inhibition of cellular protein synthesis and growth (Cazzaniga et al., 2009;Goodwin et al., 2009;Martin-Castillo et al., 2010). Moreover, metformin can directly inhibit tumor cell growth and proliferation by regulating the cyclin D1-mediated cell cycle, p53 expression, and phosphorylation in breast and pancreatic cancers (Ben, I et al., 2010;Feng et al., 2007). Metformin can also decrease the production of inflammatory cytokines, including TNF-α, IL-6, and VEGF by inactivation of NF-κB and HIF-1α (Ersoy et al., 2008;Lund et al., 2008;Huang et al., 2009). It is also possible that the anti-tumor activity of metformin in vitro and in vivo may be associated with inhibition of the insulin/IGF-1 pathway through AMPK activation (Kisfalvi et al., 2009;Rozengurt et al., 2010) by inactivation of breast CD44+/CD24− CSC cells and the EMT phenotype (Hirsch et al., 2009;Vazquez-Martin et al., 2010) or by inhibiting cell growth, clonogenic potential, migration/invasion, and CSC self-renewal capacity in gemcitabine-resistant pancreatic cancer cells (Bao et al., 2012c). It has also been found that metformin inhibits the expression of the CSC surface markers CD44 and EpCAM, expression of CSC genes such as EZH2, Notch-1, Nanog, and Oct4, and the miRNA expression of let-7 and miR-200 family in the CSC-like sphere cells of gemcitabine-resistant cells (Bao et al., 2012c). These findings indicate that the anti-tumor effects of metformin may involve the targeting of CSC subpopulations, providing additional proof in support of the importance of CSC cells in cancer."
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We monitor the success of a drug by its effect on PSA - did it meet the >50% reduction criterion? So the treatments that kill a lot of cells naturally get promoted.
Meanwhile, PCa stem cells, which produce no PCa, are ignored.
The answer I was seeking, is in the first para of your above reply which is "we know nothing about STEMNESS in cancer"and thus about the HRPC disease. Being blissfully ignorant, that should be why we play with the known devil and face death with the unknown devil whom we take for granted!
Though not relevant to the point in question, i read your long account on METFORMIN and appreciate the findings.
Thank you once again for your valuable time and also for your frequent posts which carry a great deal of useful information for all of us.
So all the hormone path treatments will never affect a certain cure. The successive elimination of the pathways for testosterone synthesis, cannot cure prostate cancer.
I did not know there was a difference between HR and CR! I’ve been on ADT3 (Lupron, casodex, dutasteride) off and on since 2015. My T is <3 and Psa is <.1 . When I stopped ADT3, Psa rose to 2.3 and T to 89 in six months which is fast doubling time. Axumin scan found femur met so I went back on ADT3 along with sbrt to met and xgeva.
So I’m very sensitive to HT and am not having a big problem being on it. I’ve also been on Snuffy Meyers regimen of metformin, statin , estradiol patches, etc. the whole time. All my blood work is good .
I’m leery about adding any other treatments as long as my PSA is under control.
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