Statin use in advanced PCA with ADT or abiraterone/enzalutamide

[pjoshea13]

New meta-analysis below [1].

Does statin use affect mortality when used with classic ADT or Zytiga/Xtandi?

Bottom line:

... statins reduced all-cause mortality by 27% & PCa-specific mortality by 36%.

"Databases were searched using keywords (abiraterone OR enzalutamide OR androgen deprivation therapy) AND statin. In total, nine eligible studies from 111 references were included for final analysis."

"Statin use significantly lowered the risk of all-cause mortality (100,709 patients, HR = 0.73 ...) and the risk of cancer-specific mortality (100,343 patients, HR = 0.64 ...) in advanced PCa patients treated with ADT. The sensitivity analysis showed that the results were reliable. However, it could not generate reliable evidence in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone/enzalutamide, as relevant studies were limited and had inconsistent results."

"The review indicated that the use of statins in combination with ADT was associated with better all-cause survival and cancer-specific survival in patients with advanced PCa."

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/319...

J Clin Pharm Ther. 2020 Jan 17. doi: 10.1111/jcpt.13092. [Epub ahead of print]

The effect of statins on advanced prostate cancer patients with androgen deprivation therapy or abiraterone/enzalutamide: A systematic review and meta-analysis.

Yang H1, Pang L2, Hu X3, Wang W3, Xu B2, Zhang X3, Liu L1.

Author information

Abstract

WHAT IS KNOWN AND OBJECTIVE:

To evaluate the effects of statin use on the treatment outcomes (i.e. overall survival and cancer-specific survival) among advanced prostate cancer (PCa) patients treated with androgen deprivation therapy (ADT) or abiraterone/enzalutamide.

METHODS:

The original studies, examining the effects of statins on the outcomes (i.e. overall survival and cancer-specific survival) among PCa patients treated with ADT or abiraterone/enzalutamide, were identified through a systematic search by two independent reviewers in the PubMed, Cochrane, Embase, American Society of Clinical Oncology and European Society of Medical Oncology databases. Databases were searched using keywords (abiraterone OR enzalutamide OR androgen deprivation therapy) AND statin. In total, nine eligible studies from 111 references were included for final analysis.

RESULTS AND DISCUSSION:

Statin use significantly lowered the risk of all-cause mortality (100 709 patients, HR = 0.73, 95%CI = 0.64-0.83, P < .00001) and the risk of cancer-specific mortality (100 343 patients, HR = 0.64, 95% CI = 0.53-0.77, P < .00001) in advanced PCa patients treated with ADT. The sensitivity analysis showed that the results were reliable. However, it could not generate reliable evidence in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone/enzalutamide, as relevant studies were limited and had inconsistent results.

WHAT IS NEW AND CONCLUSION:

The review indicated that the use of statins in combination with ADT was associated with better all-cause survival and cancer-specific survival in patients with advanced PCa. Randomized controlled trials should be conducted to establish efficacy of statins among PCa patients.

© 2020 John Wiley & Sons Ltd.

KEYWORDS:

abiraterone; androgen deprivation therapy; meta-analysis; prostate cancer; statin

PMID: 31951037 DOI: 10.1111/jcpt.13092

[LearnAll]

Patrick...Its true that statins increase CSS and all cause mortality. Is it because statins get lipid profile in ideal range thus increase longevity OR statins have some particularly specific action ...slowing cancer progression ? What is the mechanism of action?

one more question: Will statin use even benefit people whose lipids are in ideal range ?

[pjoshea13 in reply to LearnAll]

I asked my doctor for high-dose Simvastatin a dozen years ago, on the basis that:

- solid tumors (not just PCa) accumulate cholesterol

- cholesterol in PCa cells might be used to make androgen

- PCa cells can make cholesterol if uptake does not meet demand

I think it prudent to start on a statin after diagnosis, but perhaps essential to be on one during ADT, when cells are responding to a shortage of androgen.

The important point IMO, is that statins might interfere with the ability of cancer cells to manufacture cholesterol.

Men with low LDL might feel safe, but low LDL might induce adaptation earlier.

Another aspect of statins that is often ignored is that they reduce inflammation, and I believe that this might affect survival too.

-Patrick

[hansjd]

Thanks for this post Patrick. It reconfirms why I'm on 80 mg /day of Atorvastatin.

[donits in reply to hansjd]

Hi Hansjd,

I would like to ask you if you have any side effects due to Atorvastatin. How much do you take this medicine? What taste do these pills have, are they bitter, salty...? I am asking because I am participating in a clinical trial - Atorvastatin80mg/placebo +Bicalutamide. BTW, I once read on the internet that atorvastatin works better together with Celexobit for prostate cancer.

[hansjd in reply to donits]

Hi donits

I take 1 x 80 mg pill of Atorvastatin / day. No taste or side effects apparent. I'm also taking Bicalutamide. Like you, I've read about the synergistic effect of Atorvastatin with Celebrex (Celecoxib), so I also take 200 mg / twice a day of Celebrex.

[donits in reply to hansjd]

Thank you Hansjd,

I also take Celebrex, Metformin and Melatonin. I believe this will slow down the progression of cancer.

[hansjd in reply to donits]

I also take Metformin 2000 mg /day and Metformin 20 mg / day. Same belief as you that it will slow progression .... and a good deal of hope as well !

[FRTHBST in reply to donits]

I am taking 80mg Atorvastatin as part of COC program. Also added Dipyradamole sciencedirect.com/science/a... as it seems to have a synergy with Atorvastatin in preventing lipid metabolism in Pca.

[donits in reply to FRTHBST]

Thank you very much, best greetings.

[Hidden in reply to hansjd]

That seems like a lot. My PCP very reluctantly bumped my Atorvastatin dose from 10mg to 20mg at my request. That was about a month and a half ago.

[FRTHBST in reply to Hidden]

Spoke with the COC oncologist yesterday, she said 80mg Atorvastatin would be the maximum dose. As long as bloodwork shows that my liver is doing well, I can tolerate this dosage.

[6357axbz]

Patrick, do you believe atorvastatin is more effective than Crestor (rosuvastatin)? I don’t think the study specified other than Statin.

[pjoshea13 in reply to 6357axbz]

There is a PCa cell study that found that a much higher dose of Rosuvastatin (than Atorvastatin) was needed:

"Statins act directly on PC-3 cells with {atorvastatin, mevastatin, simvastatin} (1 μM) and rosuvastatin (5 μM), but not pravastatin, significantly reducing invasion towards BMS {bone marrow stroma} by an average of 66.68% (range 53.93-77.04% ...) and significantly reducing both number (76.2±8.29 vs 122.9±2.48 ...) and size (0.2±0.0058 mm(2) vs 0.27±0.012 mm(2) ...) of colonies formed within BMS." [1]

Which is perhaps no surprise since:

"Atorvastatin, lovastatin, and simvastatin are lipophilic, whereas pravastatin, rosuvastatin, and fluvastatin are more hydrophilic." [2]

There are differences of opinion regarding the ability of statin drugs to enter PCa cells, but my money's on the lipophilic.

However (from May) [3]:

"Patients who received atorvastatin {down 26%}, pravastatin, rosuvastatin {down 31%}, or pitavastatin showed a stronger reduction in mortality than those who received other statins."

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/225...

[2] medscape.com/viewarticle/56...

[3] ncbi.nlm.nih.gov/pubmed/308...

[6357axbz in reply to pjoshea13]

Thanks Patrick. I’ve been mulling over these results for many months. I’m on rosuvastatin (40 mg) for arteriosclerosis. In light of this latest study you posted I think I’ll ask my cardiologist what’s the highest dose of atorvastatin he’d prescribe in consideration of my PCa. My liver functions are all in normal range. Previously I was on atorvastatin with no ill effects but both my PCP and Cardiologist thought rosuvastatin would be more effective for lowering cholesterol.

[6357axbz in reply to pjoshea13]

Patrick, do you take atorvastatin, Curcumin, metformin?

[pjoshea13 in reply to 6357axbz]

Simvastatin (40 mg)

Curcumin (Longvida):

swansonvitamins.com/now-foo...

Metformin (2000 mg)

-Patrick

[6357axbz in reply to pjoshea13]

TY

[Hidden]

I saw where some people have concerns that statins can cause memory problems but this article says otherwise:

health.clevelandclinic.org/...