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Statin use and survival in metastatic castration-resistant PCa treated with abiraterone or enzalutamide after docetaxel failure.

pjoshea13 profile image
29 Replies

New study below [1].

I believe that in the U.S. more than half of men my age are using a statin. On the other hand, I sense antipathy towards statins among many who are not using them. Certainly, there are sites such as Mercola's that contain dire warnings.

In my case, I had no interest in lowering cholesterol, but the PCa literature suggested a benefit, so I asked my doctor for high-dose Simvastatin. He wouldn't give me Metformin, but anyone who asked could get a statin.

The new paper opens with:

"Statins may potentiate the effects of anti-hormonal agents for metastatic castration-resistant prostate cancer (mCRPC) through further disruption of essential steroidogenic processes."

A statin will reduce the availability of cholesterol to PCa cells, & prevent the cells from manufacturing it. This limits the potential for cancer cells to make androgens from cholesterol.

"Five hundred and ninety-eight patients treated with second-line abiraterone or enzalutamide after docetaxel for mCRPC were included. A total of 199 men (33.3%) received statins during abiraterone/enzalutamide treatment. Median OS was 20.8 months ... for patients who received statins, versus 12.9 months ... for patients who did not receive statins".

"After adjusting for age, alkaline phosphatase, PSA, neutrophil-to-lymphocytes ratio, Charlson comorbidity score, Gleason score, visceral disease, hemoglobin, opiate use and abiraterone versus enzalutamide treatment, the use of statin therapy was associated with a 53% reduction in the overall risk of death".

"Statin use was also associated with a 63% increased odds of a > 30% PSA decline within the first 12 weeks of treatment".

There is a case for beginning statin use at the start of ADT, or even at diagnosis, IMO. Potential benefit should increase as the screws are tightened, so it's no surprise to see the results after after Zytiga or Xtandi were added, even at such a late stage.

What was not mentioned in the Abstract is if statins increased the mean-time-to-failure of the other drugs.

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/297...

Oncotarget. 2018 Apr 13;9(28):19861-19873. doi: 10.18632/oncotarget.24888. eCollection 2018 Apr 13.

Statin use and survival in patients with metastatic castration-resistant prostate cancer treated with abiraterone or enzalutamide after docetaxel failure: the international retrospective observational STABEN study.

Gordon JA#1, Buonerba C#2,3, Pond G4, Crona D5, Gillessen S6, Lucarelli G7, Rossetti S8, Dorff T9, Artale S10, Locke JA1, Bosso D2, Milowsky MI5, Witek MS6, Battaglia M7, Pignata S11, Cherhroudi C12, Cox ME1, De Placido P2, Ribera D2, Omlin A6, Buonocore G13, Chi K14, Kollmannsberger C14, Khalaf D14, Facchini G8, Sonpavde G15, De Placido S2, Eigl BJ14, Di Lorenzo G2.

Author information

1

Vancouver Prostate Center, Vancouver Coastal Health Research Institute, Vancouver, British Columbia, Canada.

2

Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy.

3

Istituto Zooprofilattico Sperimentale del Mezzogiorno, Portici, Italy.

4

McMaster University, Hamilton, Ontario, Canada.

5

Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA.

6

Department of Medical Oncology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.

7

Department of Emergency and Organ Transplantation, Urology, Andrology and Kidney Transplantation Unit, University of Bari, Bari, Italy.

8

S.S.D Oncologia Clinica Sperimentale Uro-Andrologica, Dipartimento Corp-S Assistenziale dei Percorsi Oncologici Uro-Genitale, Istituto Nazionale Tumori Fondazione G. Pascale-IRCCS, Naples, Italy.

9

University of Southern California Keck School of Medicine, Norris Comprehensive Cancer Center, Los Angeles, California, USA.

10

Oncology Department, Ospedale di Gallarate ASST Valle Olona, Gallarate, Italy.

11

Division of Medical Oncology, Department of Uro-Gynecologi cal Oncology, Istituto Nazionale Tumori Fondazione G. Pascale-IRCCS, Naples, Italy.

12

Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.

13

Hospital Directorate, Azienda Ospedaliera Universitaria Federico II of Naples, Naples, Italy.

14

BC Cancer, Vancouver, British Columbia, Canada.

15

Genitourinary Oncology Section, Dana Farber Cancer Institute, Boston, Massachusetts, USA.

#

Contributed equally

Abstract

BACKGROUND:

Statins may potentiate the effects of anti-hormonal agents for metastatic castration-resistant prostate cancer (mCRPC) through further disruption of essential steroidogenic processes. We investigated the effects of statin use on clinical outcomes in patients with mCRPC receiving abiraterone or enzalutamide.

MATERIALS AND METHODS:

This was a retrospective multicenter study including patients that received abiraterone or enzalutamide for mCRPC. The effect of concurrent statin use on outcomes was evaluated. The associations of statins with early (≤12 weeks) prostate-specific antigen (PSA) declines (> 30%), cancer-specific survival and overall survival (OS) were evaluated after controlling for known prognostic factors.

RESULTS:

Five hundred and ninety-eight patients treated with second-line abiraterone or enzalutamide after docetaxel for mCRPC were included. A total of 199 men (33.3%) received statins during abiraterone/enzalutamide treatment. Median OS was 20.8 months (95% CI = 18.3-23.2) for patients who received statins, versus 12.9 months (95% CI = 11.4-14.6) for patients who did not receive statins (P < 0.001). After adjusting for age, alkaline phosphatase, PSA, neutrophil-to-lymphocytes ratio, Charlson comorbidity score, Gleason score, visceral disease, hemoglobin, opiate use and abiraterone versus enzalutamide treatment, the use of statin therapy was associated with a 53% reduction in the overall risk of death (hazard ratio [HR] = 0.47; 95% CI = 0.35-0.63; P < 0.001). Statin use was also associated with a 63% increased odds of a > 30% PSA decline within the first 12 weeks of treatment (OR = 1.63; 95% CI = 1.03-2.60; P = 0.039).

CONCLUSIONS:

In this retrospective cohort, statin use was significantly associated with both prolonged OS and cancer-specific survival and increased early > 30% PSA declines. Prospective validation is warranted.

KEYWORDS:

abiraterone; enzalutamide; prostate cancer; statins

PMID: 29731989 PMCID: PMC5929432 DOI: 10.18632/oncotarget.24888

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29 Replies

"Median OS was 20.8 months (95% CI = 18.3-23.2) for patients who received statins, versus 12.9 months (95% CI = 11.4-14.6) for patients who did not receive statins." I'm sold, I'm going to continue taking statins enough though my cholesterol numbers are nearly perfect. Thanks for this post Pat.

pjoshea13 profile image
pjoshea13

Nala,

Not from my GP, but I had no problem with my alt-doc who also gives me T.

-Patrick

BigRich profile image
BigRich

Patrick,

Does any of the research papers give the dosage for the daily statin?

Rich

pjoshea13 profile image
pjoshea13 in reply to BigRich

Rich,

Where different doses were considered, a higher dose was always better.

-Patrick

BigRich profile image
BigRich in reply to pjoshea13

With a higher dose, I am concerned with adverse side effects. I take 10 mg. of simvastatin, for PCa protection; in that, without a statin, my cholesterol was 110.

Rich

AlanMeyer profile image
AlanMeyer

One interesting fact about this study is that it was retrospective. I assume that means that the men taking statins were mostly or entirely NOT prescribed them for their prostate cancer but rather for cholesterol or other health issues.

The reason that seems significant to me is that we might expect the men taking statins to be generally less healthy than the men not taking them and might expect the statin population to have a worse overall survival if the statins had no effect on PCa. But the results were the opposite to that.

Alan

dress2544 profile image
dress2544

I am interested in taking statin after reading your post. At present I am on Aberaterone for my CRPC. My cholesterol levels are somewhat normal. What will be the ideal dose of statin for me?

pjoshea13 profile image
pjoshea13 in reply to dress2544

IMO you should opt for a lipophilic statin, such as Simvastatin, at the highest dose.

-Patrick

George71 profile image
George71

is red rice yeast a statin

pjoshea13 profile image
pjoshea13 in reply to George71

George,

Red yeast rice contains Lovastatin. Brands are not permitted to mention this, let alone say how much is in their product.

Red yeast supplements can contain citrinin—a chemical toxin linked to liver damage.

From 2008:

"Four out of the 10 products ConsumerLab tested contained a toxic substance called citrinin.":

reuters.com/article/us-cont...

Go for a reliable brand that guarantees no citrinin.

-Patrick

EdBar profile image
EdBar

Snuffy Myers discussed this in his book that is now over 15 years old, shows how far ahead of the curve he was/is. In my last phone consult with him prior to his retirement, we lowered my dose of Crestor because my LDL cholesterol was getting too low from the dose I was on together with a Meditteranean diet. He said a certain amount is necessary for normal brain function and that levels that are too low could add to the cognitive issues I already experience from triple ADT. I've been taking statins well before being diagnosed with PCA, Snuffy switched me to Crestor since some statins interfere with pathways used by drugs like Xtandi.

One More Cast...

Ed

pjoshea13 profile image
pjoshea13 in reply to EdBar

Ed,

While Crestor (Rosuvastatin) might be a good choice in general, it is probably not a good choice for getting to PCa cells, because it is hydrophilic, not lipophilic:

pharmacytimes.com/publicati...

-Patrick

EdBar profile image
EdBar

I don't believe Snuffy was concerned about the statin "getting to PCa", his goal was to keep LDL cholesterol levels low since PCa will convert it to testosterone/DHT when levels of T are kept low from ADT. Crestor doesn't block an important pathway used by Xtandi, I believe Simvistatin does, he discusses this in his book. I was on Simvistatin when he switched me to Crestor after our first visit.

Ed

smroush profile image
smroush

Very interesting! Thanks for posting Patrick!

CalBear74 profile image
CalBear74

pjoshea13,

As you may know, not taking Metformin, DOES NOT mean you can't benefit from the effects achieved with berberine. It is the natural equivalent of the Metformin molecule. Two capsules before a meal, about 1000 mg. before all 3 meals.

Many men who post at this site are using Metformin which has been included as adjuvant therapy in numerous cancer clinical trials. See pubmed.gov for berberine research related to prostate cancer.

I also take red yeast rice, the natural equivalent to Lovastatin. Your post nicely summarizes the payoff for statin drug users who are also experiencing prostate cancers. Recently, Taiwanese researchers focused on Lovastatin and Simvastatin users, who were fighting hyperlipidemia and found they live longer by about 2 years than nonstatin drug users. If any reader of these posts chooses to start using red yeast rice take co-q-10 with it. I have been using it for more than 20 years with no side effects. I have taken berberine for the past two years and with no side effects. I should mention that berberine lowered my A1c from 5.7 to 5.1. My LDL consistently runs in the 70's.

I am a 76 year old, G 8, stage IV PCa patient (2012), with a PSA trending lower for the last two years, currently 0.06. Lupron (6 month shots) is my only therapy. I am not yet resistant.

I take numerous other natural supplements, most importantly IP6 (inositol hexaphosphate or "phytate") per Dr. AKM Shamsuddin's protocol, and beta 1,3D glucan from Transfer Point combined with resveratrol and vitamin C per Dr. Vaclav Vetvicka's protocol. Both of these cancer researchers, affiliated with university medical schools, have books available at Amazon.com. Go to vitawithimmunity.com for an introduction to beta glucan and watch these videos to better understand both supplements.

nutritionfacts.org/video/tr...

nutritionfacts.org/video/tr...

nutritionfacts.org/video/ph...

I hope this information is helpful.

your happy vegan, CalBear74

George71 profile image
George71 in reply to CalBear74

pjoshea13 & Calbear,

Thanks for the info.

I have been taking Choleste_Rice with CoQ10 by Bluebonnet. Is that a good brand?

And can I take berberine in place of Metformin? I am having trouble with loose stool on 2000mg Metformin

CalBear74 profile image
CalBear74 in reply to George71

I have never heard of this brand George71. Which doesn't mean they aren't excellent. I use Solaray for quality reasons. I once tried out a competing brand and my LDL went up. I returned to Solaray and it dropped. They make a combo capsule with co-q-10.

I would consult your prescribing physician before making any decision involving dropping a prescribed medication. Are you getting good results (on A1c) with Metformin? That is the most important issue.

Good luck,

CalBear74

George71 profile image
George71 in reply to CalBear74

I didn't see your history -- but I am 2 years since surgery Gleason 8 -- PSA at time of surgery was 8.1 -- post surgery pathology was 4 0f 10 lymph nodes -- PSA 0.03 immediately after surgery -- then 4 months later was 0.1 -- rising to currently 0.447 -- I started Avadart and Metformin 6 months ago and the PSA has been holding @ 0.4 for 6 months. Not sure what to do. I am thinking about starting radiation of pelvic lymph nodes soon but would have to start ADT. No gene mutations found in gene testing. I am thinking if I have to go on ADT for 6 months during radiation -- I could try high /low Testosterone (BAT) -- my current T on Avadart is around 600.

What do you think?

CalBear74 profile image
CalBear74 in reply to George71

My history George: . I am a 76 year old, G 8, stage IV PCa patient (2012), with a PSA then of 19; now my PSA is trending lower for the last two years, currently 0.06. Lupron is my only therapy since we arrived here in Florida in fall, 2016. Prior to that, I was on Casodex and Lupron in AZ since my diagnosis in November, 2012. My career was in hospital marketing and planning; I left after 12 years and went with a medical software company specializing in health promotion and clinical triage.

I take numerous other natural supplements, most importantly IP6 (inositol hexaphosphate or "phytate") per Dr. AKM Shamsuddin's protocol, and beta 1,3D glucan from Transfer Point combined with resveratrol and vitamin C per Dr. Vaclav Vetvicka's protocol. Both of these cancer researchers, affiliated with university medical schools, have books available at Amazon.com. Go to vitawithimmunity.com for an introduction to beta glucan and watch these videos to better understand both supplements.

nutritionfacts.org/video/tr...

nutritionfacts.org/video/tr...

nutritionfacts.org/video/ph...

I hope this information is helpful.

your happy vegan, CalBear74

George71 profile image
George71 in reply to CalBear74

That is a great record. Did you have mets in bones or nodes?

CalBear74 profile image
CalBear74 in reply to George71

Sorry George I missed this question when you first posted it. I have two mets identified in late 2012 on my pelvic bone. In the summer of 2017 I had another scan and they couldn’t identify The bone Mets. I believe this was a result of two years of IP6.However in 2017 they did identify one met on my left pelvic lymph node. That may have been there in 2012 but the radiologist was not confident of his images.

CalBear74 profile image
CalBear74 in reply to George71

George,

I provided dead links. Sorry.

These should do better:

nutritionfacts.org/video/ph...

nutritionfacts.org/video/tr...

nutritionfacts.org/video/tr...

CalBear74

CalBear74 profile image
CalBear74 in reply to George71

How are things going George? Looking back over your posts I realized I was quite careless in responding. Have you had your testosterone level measured recently?

George71 profile image
George71 in reply to CalBear74

Hi CalBear74,

Thanks for the reply. My T level is 480 to 550.

in reply to CalBear74

Which brand berberine do you take?my husband is taking 1500mg with no differeception in blood sugar level.

CalBear74 profile image
CalBear74 in reply to

I take 2000 mg of Solaray berberine before each meal. That’s a total of 6000 mg daily. I am also taking red yeast from rice 1200 mg in the morning and 1200 mg in the evening before my meals. This is to control my LDL level but I believe it may also contribute to my blood sugar management . I take the Solaray brand.

j-o-h-n profile image
j-o-h-n

Anyone here know who "Vitamin Flintheart" was? If you do please raise your hand (no googling please).

Good Luck and Good Health.

j-o-h-n Thursday 05/10/2018 5:43 PM EDT

CalBear74 profile image
CalBear74 in reply to j-o-h-n

Are you ever going to tell us who Vitamin Flintheart is? My hand is raised.

j-o-h-n profile image
j-o-h-n

🤬 He was a cartoon character in the old Dick Tracy newspaper comic strip. Okay now you can lower your hand.

Good Luck, Good Health and Good Humor.

j-o-h-n Thursday 01/24/2019 5:25 PM EDT

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