Statins for Prostate Cancer

Overseen By Jasmin M Brooks

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Medical University of South Carolina

Must not be taking: Statins, Fibrates, Niacin, others

Disqualifiers: Diabetes, Metastases, Liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 8 weeks

36 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will evaluate whether simvastatin reduces intraprostatic immunosuppressive microenvironment through YAP-mediated T-reg dysfunction, and increases intraprostatic anti-tumor immune response in men recently diagnosed with localized prostate cancer electing to receive prostatectomy for their care. Half the men will be randomized to receive statins for 8 weeks prior to their surgery, while the other half will receive standard of care.

Do I have to stop taking my current medications for the trial?

You may need to stop certain medications. If you are currently using statins, non-statin lipid-lowering drugs, or medications that are contraindicated with simvastatin, you cannot participate. These include drugs like gemfibrozil, cyclosporine, and certain antibiotics and antifungals. If you are on medications that require a lower dose of simvastatin, like verapamil or diltiazem, you may also be excluded. The protocol does not specify a washout period.

What data supports the idea that Statins for Prostate Cancer (also known as: Simvastatin, Zocor, Simvastatin) is an effective treatment?

The available research shows that simvastatin, a type of statin, can be effective in treating prostate cancer. One study found that simvastatin reduced tumor growth in mice and lowered levels of a protein linked to prostate cancer. Another study suggested that simvastatin might help kill cancer cells by affecting certain pathways in the cells. However, some research indicates that the drug's effects might be more related to lowering cholesterol rather than directly stopping cancer growth. Overall, while there is some evidence supporting the use of simvastatin for prostate cancer, more research is needed to fully understand its effectiveness. ^{1 2 3 4 5}

What safety data exists for using simvastatin in prostate cancer treatment?

The provided research does not directly address safety data for simvastatin in prostate cancer treatment. However, it discusses the potential therapeutic benefits and mechanisms of simvastatin, including its effects on apoptosis, cell proliferation, and tumor growth in prostate cancer models. The studies highlight simvastatin's role in inhibiting pathways like Akt and androgen receptor signaling, which are relevant to prostate cancer progression. While these findings suggest therapeutic potential, specific safety data or adverse effects are not detailed in the abstracts. ^{1 4 6 7 8}

Is the drug simvastatin a promising treatment for prostate cancer?

Yes, simvastatin shows promise as a treatment for prostate cancer. It can slow down tumor growth, reduce cancer cell spread, and lower prostate-specific antigen (PSA) levels, which are markers of prostate cancer. It also helps in blocking pathways that cancer cells use to grow and survive. ^{1 3 4 6 8}

Research Team

Michael Marrone, PhD

Principal Investigator

Public Health Sciences

Eligibility Criteria

This trial is for men with intermediate to high-risk localized prostate cancer who are planning a prostatectomy. They must not have used statins in the past year, have no history of severe reactions to statins, no metastases or diabetes, normal liver function and cholesterol levels above 50mg/dL, and not be on certain other medications.

Inclusion Criteria

I am a man with prostate cancer at intermediate or high risk of recurrence.

Ability to provide written informed consent and willing to complete study procedures

I have chosen to have surgery to remove my prostate.

Exclusion Criteria

I am currently taking medication to lower my cholesterol.

My LDL cholesterol is below 50mg/dL.

I am currently taking medications that interact with simvastatin.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 40 mg oral simvastatin daily for eight weeks prior to prostatectomy

8 weeks

2 visits (in-person) for clinical laboratory assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Simvastatin

Trial Overview The study tests if simvastatin can alter immune responses within the prostate by affecting T-reg cells in men undergoing surgery for prostate cancer. Participants will either receive simvastatin for 8 weeks before their operation or follow standard care without statins.

Participant Groups

Group I: Simvastatin Experimental Treatment 1 Intervention

Patients randomized to the statin group will receive 40 mg oral simvastatin QD for eight weeks prior to prostatectomy, including the day of surgery.

Group II: Control Active Control 1 Intervention

Patients randomized to the control group receive no intervention prior to prostatectomy.

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

Findings from Research

Simvastatin, a common cholesterol-lowering drug, has shown promising therapeutic effects against prostate cancer by inhibiting the Akt pathway, which is crucial for cell growth and survival, in both androgen-dependent and androgen-independent prostate cancer cells.

In a study using a PC3 xenograft model in mice, simvastatin treatment led to reduced tumor growth and lower prostate-specific antigen (PSA) levels, indicating its potential as a treatment option for prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anticancer efficacy of simvastatin on prostate cancer cells and tumor xenografts is associated with inhibition of Akt and reduced prostate-specific antigen expression. Kochuparambil, ST., Al-Husein, B., Goc, A., et al.[2013]

Simvastatin induces apoptosis in prostate cancer cells by inhibiting the intrinsic survival pathway, which involves enhancing the phosphorylation of Bad and reducing levels of pro-survival proteins like Bcl-2 and Bcl-xL.

The study also shows that simvastatin activates the extrinsic apoptosis pathway by increasing the expression of molecules such as TNF and Fas-L, suggesting that statins could be promising anti-cancer agents by targeting multiple apoptotic pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous modulation of the intrinsic and extrinsic pathways by simvastatin in mediating prostate cancer cell apoptosis. Goc, A., Kochuparambil, ST., Al-Husein, B., et al.[2022]

In a study comparing high-dose and therapeutic-dose simvastatin on prostate cells, simvastatin was found to inhibit the growth of normal prostate cells more effectively than cancer cells, suggesting a potential selective effect.

The research indicates that the growth-inhibiting effects of simvastatin may not occur at standard clinical doses, as LDL-cholesterol can reverse these effects, implying that any benefits of statins in prostate cancer might be linked to their cholesterol-lowering properties rather than direct anti-cancer effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effects of high and low-dose simvastatin on prostate epithelial cells: the role of LDL. Murtola, TJ., Syvälä, H., Pennanen, P., et al.[2017]

Simvastatin effectively reduces the viability of castrate-resistant prostate cancer cells (PC3 and DU-145) and increases apoptosis in a dose- and time-dependent manner, indicating its potential as a therapeutic agent.

The mechanism of action involves the inhibition of the nuclear factor-κB (NF-κB) pathway, specifically by preventing IκBα phosphorylation and nuclear translocation of the p50/p65 dimer, which leads to decreased expression of anti-apoptotic proteins.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simvastatin induces apoptosis in castrate resistant prostate cancer cells by deregulating nuclear factor-κB pathway. Park, YH., Seo, SY., Lee, E., et al.[2016]

Statin use in advanced prostate cancer patients undergoing androgen deprivation therapy (ADT) was associated with a significant reduction in all-cause mortality (HR = 0.73) and cancer-specific mortality (HR = 0.64), based on a systematic review of nine studies involving over 100,000 patients.

While statins showed promising benefits for patients treated with ADT, the evidence for their efficacy in those with metastatic castration-resistant prostate cancer (mCRPC) receiving abiraterone or enzalutamide was inconclusive, highlighting the need for further randomized controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of statins on advanced prostate cancer patients with androgen deprivation therapy or abiraterone/enzalutamide: A systematic review and meta-analysis. Yang, H., Pang, L., Hu, X., et al.[2021]

Novel simvastatin-related compounds, particularly SVA, effectively suppress tumor growth in various prostate cancer cell lines by inhibiting cell proliferation, migration, and inducing apoptosis, showing promise as a treatment for castration-resistant prostate cancer.

These compounds not only block androgen receptor signaling but also inhibit the AKT pathway, suggesting a multifaceted mechanism of action that enhances their therapeutic potential, especially when combined with docetaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Statin derivatives as therapeutic agents for castration-resistant prostate cancer. Ingersoll, MA., Miller, DR., Martinez, O., et al.[2018]

In a study involving 90 male nude mice with prostate cancer, the combination of simvastatin and ezetimibe actually accelerated tumor growth, suggesting that these cholesterol-lowering drugs may not be effective in slowing prostate cancer progression.

Ezetimibe reduced serum cholesterol levels by 15%, but paradoxically led to higher cholesterol levels in tumors, indicating that prostate tumors may adapt by increasing low-density lipoprotein receptors, which could be a mechanism of resistance against cholesterol-lowering therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence for Feedback Regulation Following Cholesterol Lowering Therapy in a Prostate Cancer Xenograft Model. Masko, EM., Alfaqih, MA., Solomon, KR., et al.[2020]

The combination of the AR antagonist darolutamide and the statin simvastatin significantly suppressed the growth of castration-resistant prostate cancer (CRPC) cells, particularly in androgen-independent LNCaP-LA and 22Rv1 cell lines, indicating a potential new treatment strategy.

Simvastatin not only reduced the expression of androgen-stimulated genes but also altered the expression of key cell cycle regulators, suggesting that this combination therapy may target CRPC growth through both androgen-dependent and independent pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination therapy with novel androgen receptor antagonists and statin for castration-resistant prostate cancer. Nakayama, H., Sekine, Y., Oka, D., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Anticancer efficacy of simvastatin on prostate cancer cells and tumor xenografts is associated with inhibition of Akt and reduced prostate-specific antigen expression. [2013]

2. England pubmed.ncbi.nlm.nih.gov

Simultaneous modulation of the intrinsic and extrinsic pathways by simvastatin in mediating prostate cancer cell apoptosis. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Comparative effects of high and low-dose simvastatin on prostate epithelial cells: the role of LDL. [2017]

4. United States pubmed.ncbi.nlm.nih.gov

Simvastatin induces apoptosis in castrate resistant prostate cancer cells by deregulating nuclear factor-κB pathway. [2016]

5. England pubmed.ncbi.nlm.nih.gov

The effect of statins on advanced prostate cancer patients with androgen deprivation therapy or abiraterone/enzalutamide: A systematic review and meta-analysis. [2021]

6. Ireland pubmed.ncbi.nlm.nih.gov

Statin derivatives as therapeutic agents for castration-resistant prostate cancer. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Evidence for Feedback Regulation Following Cholesterol Lowering Therapy in a Prostate Cancer Xenograft Model. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Combination therapy with novel androgen receptor antagonists and statin for castration-resistant prostate cancer. [2022]