Prednisone/Prednisolone & Dexamethasone are corticosteroids - steroid hormones that "have been used in the therapy for castration-resistant prostate cancer (CRPC) for decades, both as monotherapy and in combination with additional agents." [2]
"... prednisone is distinctly different from prednisolone, but is converted to prednisolone by hepatic enzymes."
A 2015 paper [2] details a Phase II study "among chemotherapy naïve CRPC patients who had not received prior abiraterone or enzalutamide therapy."
"In an intent-to-treat analysis 41% of patients in the dexamethasone arm achieved a PSA response, while only 22% of patients in the prednisolone arm achieved a PSA response."
"Interestingly, 23 of the 36 patients randomized to prednisolone crossed over to dexamethasone at PSA progression and 19 of those patients were evaluable for PSA response. Seven of these patients (37%) achieved a PSA response to dexamethasone, which suggests a potential role for dexamethasone even after progression on prednisone therapy."
The new study (U.K., Royal Marsden) involved "75 chemotherapy and abiraterone/enzalutamide-naive CRPC patients."
The Neutrophil to Lymphocyte Ratio [NLR] is a measure of inflammation. Markers of inflammation are associated with poorer oucome. {In every situation - even when disease has not been diagnosed. Chronic low-level inflammation is something that everyone should test for & treat IMO.}
"The median NLR for all evaluable patients was 2.6 at baseline; 2.9 at 6 weeks; and 4.0 at 12 weeks." i.e. treatment increased inflammation.
"A favorable baseline NLR (less than median) associated with a 5.5-fold higher odds of a PSA >50% response"
"Higher baseline NLR (log10) associated with a shorter time to PSA progression" - risk factor = 9.5.
"NLR at 6 weeks was also associated with duration of benefit; in the favorable NLR category time to PSA progression was 10.8 months, for those who converted to an unfavorable (greater than median) category 4.5 months, and for those remaining in a unfavorable category only 1.5 months"
"Overall survival was 33.1 months ... and 21.9 months ... for those with an favorable and unfavorable baseline NLR, respectively."
Inflammation kills. My contention is that, while the disease can ramp up inflammation (via NF-kB activation), inflammation can be treated, independentantly of the disease.
"Treatment-naive CRPC patients with a high baseline or during-treatment NLR appear not to benefit from low-dose corticosteroids. The immunological implications of an unfavorable NLR, and whether corticosteroids might drive prostate cancer progression in patients harboring a high NLR, warrant further study."
...
Zytiga is usually coupled with prednisone. I don't know if Zytiga has been studied with dexamethasone. We tend to forget that the corticosteroid also has anti-Pca activity.
Could you restate your summary of this study and how it might inform treatment decisions? It was a little too abstract for me to follow. LOL
I had some heavy duty radiation treatment at the Dattolli center that included treatment of not only my prostate but also some lymph nodes. The net result is that it killed off most of my cb4 T cells.
It seems like maybe this study might have some relevance to me, but I just could not quite follow it.
2] If considering corticosteroids as monotherapy, there may be no benefit if NLR is high or becomes high.
3] It isn't proven that corticosteroids will actually worsen cases where the NLR is high, but the the study suggests it as a possibility.
4] How would I control NLR? I would throw polyphenols at it. High-potency curcumin & resveratrol (CurcuBrain & Nitro250), apigenin, fisetin, pomegranate extract, CranMax & any of a dozen others. Take high doses. They are all NF-kB inhibitors & NF-kB is chronically activated in PCa. Monitor NLR & adjust dose if necessary.
Nalakrats likes Zyflamend, but he does use other stuff too.
-Patrick
pjoshea13 -- Thanks, Patrick, but I'm a bit confused by these 2 statements, one from you and the other from the article:
From you: We tend to forget that the corticosteroid also has anti-Pca activity.
From the article: "... corticosteroids might drive prostate cancer progression..."
Corticosteroids are powerful anti-inflammatories, so why should they promote progression? Since the prednisone given along with Zytiga is low dose, it shouldn't be immunosuppressive, in my understanding.
The confusing thing to me is why anti-inflammatory corticosteroids would increase the NLR, a common inflammation marker. & yet that seems to have happened.
About a year ago I posted a similar finding with Xtandi:
"The median baseline NLR was 3.2."
"The median {overall survival} was 10.4 months ... in patients with baseline NLR >3 and 16.9 months ... in those with baseline NLR ≤3"
"In multivariate analysis, changes in NLR at 4 weeks were significant predictors of both {Progression-free survival} [hazard ratio (HR) 1.24 ..., and {overall survival} (HR 1.29 ...)"
"A persistent NLR >3 during treatment with enzalutamide seems to have both A persistent NLR >3 during treatment with enzalutamide seems to have both prognostic and predictive value in CRPC patients. value in CRPC patients."
In other words, the only way to go through treatment optimally is with the lowest NLR you can manage. & it seems that it should be tracked monthly, because treatment might increase it.
In the new study, crossing over into high NLR could have a significant effect on survival.
You make a good point about dosage - I didn't compare doses for monotherapy & when used with Zytiga.
Ultimately, the new paper simply adds to the PCa-NLR literature. We need to monitor it & take corrective action if it is high.
I think readers here on this Forum should know that the supplements mentioned here and elsewhere for the purpose of reducing NLR are not generally accepted as effective from the viewpoint of medical oncologists. I have personally asked two prominent oncologists (one at MSKCC and the other at Mt. Sinai in Manhattan) if there was anything that could be done to lower NLR and their response was, "No, there is no way to lower NLR."
Polyphenols inhibit NF-kB if the dose is high enough. e.g. Apigenin.
"... activation of NF-kappa B in BMDMs collected from gamma-irradiated mice that received apigenin was suppressed at both harvest times. Further, the levels of pro-inflammatory cytokines in gamma-irradiated mice treated with 20 or 40mg/kg body weight apigenin were significantly lower than those in mice receiving radiation only (p<0.01 or <0.05) even at day 10 post-irradiation. Additionally, the ratio of neutrophils to lymphocytes indicated that apigenin ameliorated radiation-induced hematological toxicity. "
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