Advanced Prostate Cancer
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Zytiga + Statins in CRPC

New study below.

This study kicked off with a negative hypothesis:

"Statins compete with DHEAS for influx through the SLCO2B1 transporter, which may prolong time to progression (TTP) on androgen deprivation therapy. Abiraterone acetate (AA) may also undergo SLCO-mediated transport. Based on preclinical findings showing antagonism, we hypothesized that statins may compete with AA for influx via SLCO2B1 and could negatively impact drug efficacy."

Not so!

"Contrary to our initial hypothesis, there was a trend toward longer (rather than shorter) AA duration in statin users in the entire {Dana-Farber Cancer Institute} cohort {14.2 versus 9.2 months} and in the enzalutamide- and docetaxel-naïve {Johns Hopkins University} patients. Together, these results do not support the hypothesis that statins interfere with AA efficacy."

No mention of dose, though. Perhaps not enough men in the study to do a sub-analysis. But we really need to see how benefit increases with dose. If any statin use inproves time on Zytiga by 50%, what are the percentage benefits for high-dose versus low-dose?

-Patrick

ncbi.nlm.nih.gov/pubmed/287...

Prostate. 2017 Aug 1. doi: 10.1002/pros.23390. [Epub ahead of print]

The impact of statin use on the efficacy of abiraterone acetate in patients with castration-resistant prostate cancer.

Harshman LC1, Werner L2, Tripathi A1, Wang X1, Maughan BL3, Antonarakis ES3, Nakabayashi M1, McKay R1, Pomerantz M1, Mucci LA4, Taplin ME1, Sweeney CJ1, Lee GM1, Kantoff PW1,5.

Author information

1

Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.

2

Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.

3

Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.

4

Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.

5

Memorial Sloan Kettering Cancer Center, New York, New York.

Abstract

BACKGROUND:

Statins compete with DHEAS for influx through the SLCO2B1 transporter, which may prolong time to progression (TTP) on androgen deprivation therapy. Abiraterone acetate (AA) may also undergo SLCO-mediated transport. Based on preclinical findings showing antagonism, we hypothesized that statins may compete with AA for influx via SLCO2B1 and could negatively impact drug efficacy.

METHODS:

We queried two institutional clinical databases (Dana-Farber Cancer Institute [DFCI], Johns Hopkins University [JHU]) for CRPC patients treated with AA. Treatment duration was a surrogate for TTP. Associations between statin use and AA duration were estimated using the Kaplan-Meier method. Multivariable Cox regression modeling adjusted for known prognostic factors.

RESULTS:

Of the 224 DFCI and 270 JHU patients included, the majority (96%) had metastatic disease. Nearly half (41% and 45%) were statin users. In the DFCI cohort, there was a trend toward longer AA duration in statin users: 14.2 versus 9.2 months (HR 0.79, 95%CI: 0.57-1.09, P = 0.14). There was no association between statin use and AA duration in the JHU cohort: 8.3 versus 8.0 months (HR 0.89, 95%CI: 0.69-1.16, P = 0.38) in the statin users versus non-users, except for a trend in patients that had not previously received docetaxel or enzalutamide (HR 0.79; 95%CI: 0.57-1.10).

CONCLUSIONS:

Contrary to our initial hypothesis, there was a trend toward longer (rather than shorter) AA duration in statin users in the entire DFCI cohort and in the enzalutamide- and docetaxel-naïve JHU patients. Together, these results do not support the hypothesis that statins interfere with AA efficacy.

© 2017 Wiley Periodicals, Inc.

KEYWORDS:

SLCO transport; abiraterone acetate; duration; prostate cancer; statins

PMID: 28762529 DOI: 10.1002/pros.23390

3 Replies
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Is DHEA bad for someone with prostate cancer?

Reply

It's useful to have a rough idea of how steroid hormones come about:

en.wikipedia.org/wiki/Stero...

As you can see from the chart, the path to DHEA is:

... cholesterol ... pregnenolone ... DHEA (Dehydroepiandrosterone) ...

DHEA can end up as testosterone [T] via two paths, but it can also end up as estrogen (estrone or estradiol).

If you are on ADT, DHEA is obviously not a good idea, since it can convert to T.

Zytiga prevents pregnenolone from converting to DHEA, so if you are on ADT+Zytiga, DHEA is even more not a good supplement.

But for someone with PCa who is not on ADT, DHEA might be useful sometimes, I feel.

Some ask why take DHEA when you don't know how it will end up? I think that the body will figure out what to do with it.

When we are young, we have a ton of DHEA:

"Blood levels of DHEA peak in one’s twenties and then decline dramatically with age, decreasing to 20-30% of peak youthful levels between the ages of 70 and 80." [1]

It's natural to want to restore DHEA levels - low levels are associated with aging.

Not all DHEA converts to T or estrogen. Most of our DHEA is in sulphated form (DHEA-S), where it forms a reservoir for use when needed.

For men with low T (associated with worse PCa prognosis) DHEA may help increase T.

"DHEA also has a variety of potential biological effects in its own right, binding to an array of nuclear and cell surface receptors, and acting as a neurosteroid and neurotrophin." [2]

DHEA is not bad for PCa, IMO, but once one goes down the ADT path, we need to stay away from:

- DHEA

- Progesterone

- Pregnenolone

-Patrick

[1] lifeextension.com/magazine/...

[2] en.wikipedia.org/wiki/Dehyd...

Reply

Patrick, thanks for your ever informative posts and for taking the time to respond. I am off ADT as of a couple of months ago. At 67 age is catching up to me. I'd be afraid to use direct T supplementation (although I know your views on low T being a contributing factor) but maybe some indirect boosters like DHEA could be something I try. Thanks.

Ed

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