Lisinopril for Preventing Urinary Side Effects in Prostate Cancer Radiotherapy

Overseen By Therese Smudzin

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: University of Rochester

Must not be taking: Lisinopril, RAS modifiers

Disqualifiers: Prior pelvic radiotherapy, others

No Placebo Group

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This study will establish the preferred dose of lisinopril in men with non-metastatic prostate cancer undergoing radiation treatment. This study will also evaluate the effect of lisinopril on urinary symptoms and the impact of lisinopril on biomarkers and their association with urinary symptoms.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be taking lisinopril or similar drugs within two months before joining the study.

What data supports the effectiveness of the drug Lisinopril in preventing urinary side effects during prostate cancer radiotherapy?

Research shows that Lisinopril, an angiotensin-converting enzyme inhibitor, can reduce radiation injury in normal tissues, as seen in studies with rats. This suggests it might help protect against side effects during prostate cancer radiotherapy. ^{1 2 3 4 5}

How does the drug Lisinopril differ from other treatments for preventing urinary side effects in prostate cancer radiotherapy?

Lisinopril is unique because it is primarily used to treat high blood pressure and heart failure, but in this trial, it is being explored for its potential to prevent urinary side effects during prostate cancer radiotherapy, which is not a common use for this drug. ^{6 7 8 9 10}

Eligibility Criteria

Men under 70 with non-metastatic prostate cancer who are set for radiation therapy at Wilmot Cancer Institute can join. They must be in good health, able to follow the study plan, have normal kidney and liver function, not have had pelvic radiotherapy before, and not be on lisinopril or similar drugs recently.

Inclusion Criteria

I've been mostly active and able to care for myself in the past 6 months.

My cancer has not spread to distant parts of my body.

I am mentally and physically able to follow the study's requirements.

Exclusion Criteria

Have had a prior allergic reaction to lisinopril

I have had radiation therapy to my pelvic area before.

I have been taking lisinopril or a similar drug in the last two months.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants undergo radiation treatment for prostate cancer

6-8 weeks

Weekly visits during radiation

Treatment

Participants receive lisinopril to determine the preferred dose for preventing urinary toxicity

Concurrent with radiation

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Visits at 1 month, 3 months, 6 months, and 12 months post-radiation

Treatment Details

Interventions

• Lisinopril (ACE Inhibitor)

Trial Overview The trial is testing different doses of Lisinopril tablets to find the best one for preventing urinary problems after radiation treatment for prostate cancer. It will also look at how Lisinopril affects certain biomarkers related to these urinary symptoms.

Participant Groups

Group I: Intervention group Experimental Treatment 1 Intervention

Group II: Control group Active Control 1 Intervention

Patients who receive radiation but no intervention

Who Is Running the Clinical Trial?

University of Rochester

Lead Sponsor

Trials

883

Recruited

555,000+

Medical College of Wisconsin

Collaborator

Trials

645

Recruited

1,180,000+

Findings from Research

In a study using A549 cell xenografts in athymic mice, ramipril did not change the response of tumors to radiation treatment, regardless of whether it was administered before or after radiation.

However, ramipril significantly reduced radiation injury in normal tissues, suggesting it may provide a therapeutic advantage by protecting healthy cells while not affecting tumor response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential radiation effect in tumor and normal tissue after treatment with ramipril, an angiotensin-converting enzyme inhibitor. Kohl, RR., Kolozsvary, A., Brown, SL., et al.[2013]

Prostate cancer treatments, such as GnRH agonists and enzalutamide, can increase the risk of hypertension, which is a significant cardiovascular risk factor that can lead to serious complications like heart failure and stroke.

The paper recommends individualized blood pressure targets for prostate cancer patients, suggesting a goal of 130/80 mmHg while considering other health issues like frailty and existing comorbidities to guide antihypertensive treatment choices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Intersection of Prostate Cancer and Hypertension: a Call to Action. Dolmatova, E., Waheed, N., Olson, BM., et al.[2023]

A meta-analysis of seven randomized clinical trials involving 7347 patients found that enzalutamide, a treatment for prostate cancer, is associated with a significant risk of hypertension, with an overall incidence of 11.9%.

The risk of developing high-grade hypertension was also notable, with a relative risk of 2.27, indicating that patients on enzalutamide are more likely to experience severe hypertension compared to those not receiving the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased Risk of Hypertension with Enzalutamide in Prostate Cancer: A Meta-Analysis. Zhu, X., Wu, S.[2021]

In a pilot study of 26 prostate cancer patients experiencing acute radiation urethritis, Flomax (tamsulosin HCl) demonstrated an initial response rate of 62% at a 0.4 mg dose, with overall urinary symptom control achieved in 77% of patients after adjusting doses.

The presence of benign prostatic hyperplasia (BPH) was a potential predictor of a better initial response to Flomax, suggesting that certain patient characteristics may influence treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tamsulosin palliates radiation-induced urethritis in patients with prostate cancer: results of a pilot study. Prosnitz, RG., Schneider, L., Manola, J., et al.[2019]

In a study using PC-3 human prostate cancer cells and an animal model, combining radiotherapy (RT) with naftopidil significantly delayed tumor growth more effectively than either treatment alone.

The combination therapy also suppressed the upregulation of the antioxidant enzyme manganese superoxide dismutase (MnSOD), which is often increased in response to RT, suggesting that naftopidil may enhance the effectiveness of RT by targeting protective mechanisms in cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination treatment with naftopidil increases the efficacy of radiotherapy in PC-3 human prostate cancer cells. Iwamoto, Y., Ishii, K., Kanda, H., et al.[2018]

In a study of 108 patients undergoing radical external beam radiotherapy for localized prostate cancer, the use of the α-blocker tamsulosin significantly reduced the incidence of acute urinary retention (AUR) compared to a control group, indicating its efficacy in managing radiotherapy-induced urinary symptoms.

While tamsulosin improved patient-reported symptoms, the study found no independent predictive factors to identify which patients would benefit most from the treatment, suggesting that its use should be considered selectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A-blockers for the management of lower urinary tract symptoms in patients with prostate cancer treated with external beam radiotherapy: a randomized controlled study. Tsirkas, K., Zygogianni, A., Kougioumtzopoulou, A., et al.[2021]

References

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

Differential radiation effect in tumor and normal tissue after treatment with ramipril, an angiotensin-converting enzyme inhibitor. [2013]

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

The Intersection of Prostate Cancer and Hypertension: a Call to Action. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Increased Risk of Hypertension with Enzalutamide in Prostate Cancer: A Meta-Analysis. [2021]

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

Increased tumor response to neoadjuvant therapy among rectal cancer patients taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. [2022]

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

Delayed Effects of Acute Radiation Exposure (Deare) in Juvenile and Old Rats: Mitigation by Lisinopril. [2020]

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

Tamsulosin palliates radiation-induced urethritis in patients with prostate cancer: results of a pilot study. [2019]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Phosphodiesterase-5 inhibitors could be efficacious in the treatment of erectile dysfunction after radiotherapy for prostate cancer: a systematic review and meta-analysis. [2018]

8. Germany pubmed.ncbi.nlm.nih.gov

Combination treatment with naftopidil increases the efficacy of radiotherapy in PC-3 human prostate cancer cells. [2018]

9. Germany pubmed.ncbi.nlm.nih.gov

A-blockers for the management of lower urinary tract symptoms in patients with prostate cancer treated with external beam radiotherapy: a randomized controlled study. [2021]

10. Germany pubmed.ncbi.nlm.nih.gov

Clinical efficacy of combination therapy with an alpha blocker and low-dose sildenafil on post-therapy lower urinary tract symptoms after low-dose-rate brachytherapy for prostate cancer. [2022]