Atorvastatin for Hearing Loss in Head and Neck Cancer

Recruiting at3 trial locations

Overseen by Lisa L Cunningham, Ph.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: National Institute on Deafness and Other Communication Disorders (NIDCD)

Must be taking: Statins

Must not be taking: Cimetidine, Spironolactone, others

Disqualifiers: Liver disease, Kidney disease, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

Background: Cisplatin is used to treat head and neck cancer. People who take this drug are at risk for hearing loss. Atorvastatin is a drug used to treat high cholesterol. It might reduce the risk of cisplatin-induced hearing loss. Objective: To find out if atorvastatin reduces hearing loss in people treated with cisplatin and radiation. Eligibility: People ages 18 and older with squamous cell carcinoma of the head and neck who will undergo treatment with cisplatin-based chemotherapy and radiation Design: Participants will be screened with their medical records. Participants currently taking a cholesterol-lowering statin medication are invited to participate in the observational arm of the study. Those not taking such a medication are invited to participate in the interventional arm of the study. All participants will have 3 study visits for the purpose of evaluating hearing. One before starting cisplatin treatment, one within 3 months of completing cancer treatment, and one within 2 years of completing cancer treatment. They will have tympanograms. A small flexible tip will be placed in the ear canal. A puff of air will be delivered to assess mobility of the ear drum. They will have hearing tests. They will wear headphones. They will listen to tones that vary in loudness. They will be asked to indicate when they hear a sound. They will complete 3 questionnaires at the time of each hearing test. Participants will have 2 visits for blood tests. These will occur upon consent and 12 weeks after. They will be randomly assigned to take the study drug or placebo orally, once daily. They will take it during cisplatin treatment and for 3 months after treatment. Long-term follow up will include a chart review 2 years after participants complete their cisplatin therapy.

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 participate if you are currently taking a statin drug or certain other medications like cimetidine or spironolactone. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the drug Atorvastatin for preventing hearing loss in head and neck cancer patients?

Research shows that patients using atorvastatin had a lower rate of hearing loss caused by cisplatin, a common cancer drug, compared to those not using atorvastatin. This suggests atorvastatin may help protect against hearing loss in these patients. ^{1 2 3 4 5}

Is atorvastatin safe for humans?

Atorvastatin, commonly known as Lipitor, has been used for many years to manage cholesterol levels and has a reliable safety profile in humans. It is generally considered safe, and studies suggest it may also help reduce hearing loss caused by certain cancer treatments. ^{1 2 4 6 7}

How does atorvastatin differ from other drugs for hearing loss in head and neck cancer?

Atorvastatin is unique because it is primarily a cholesterol-lowering drug, but it has been found to reduce hearing loss caused by cisplatin, a common cancer treatment. Unlike other treatments, atorvastatin may help protect hearing without being specifically designed for this purpose. ^{1 4 5 7 8}

Research Team

Lisa L Cunningham, Ph.D.

Principal Investigator

National Institute on Deafness and Other Communication Disorders (NIDCD)

Eligibility Criteria

This trial is for adults with squamous cell carcinoma of the head and neck who will undergo cisplatin-based chemotherapy and radiation. They must be able to take oral medication, agree to use effective contraception if applicable, and not be on statins or have certain medical conditions that could interfere with the study.

Inclusion Criteria

I have squamous cell carcinoma of the head and neck and will be treated with specific chemotherapy and radiation.

Your blood test results for AST, ALT, CPK, and creatinine are too low.

For females of reproductive potential: use of highly effective contraception for at least 1 month prior to enrollment and agreement to use such a method during study participation and for an additional 8 weeks after the end of atorvastatin administration

Exclusion Criteria

Known allergic reactions to components of atorvastatin or the placebo

Pregnancy, lactation, or plan to become pregnant

I am currently taking a statin medication.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Treatment

Participants receive cisplatin-based chemotherapy and radiation, with atorvastatin or placebo administered daily

12 weeks

3 visits (in-person) for hearing evaluation, 2 visits for blood tests

Follow-up

Participants are monitored for safety and effectiveness after treatment, including hearing tests and chart reviews

2 years

1 visit (in-person) within 3 months, 1 visit (in-person) within 2 years

Long-term follow-up

Long-term follow-up includes a chart review 2 years after participants complete their cisplatin therapy

2 years

Treatment Details

Interventions

• Atorvastatin (HMG-CoA reductase inhibitor)
• Placebo (Other)

Trial Overview The trial is testing whether atorvastatin can prevent hearing loss in patients treated with cisplatin for head and neck cancer. Participants are randomly assigned to receive either atorvastatin or a placebo daily during treatment and for three months after.

Participant Groups

Group I: 1 Experimental Treatment 2 Interventions

Atorvasatatin (40 mg)

Group II: 2 Placebo Group 1 Intervention

Placebo

Who Is Running the Clinical Trial?

National Institute on Deafness and Other Communication Disorders (NIDCD)

Lead Sponsor

Trials

377

Recruited

190,000+

Joshua M. Levy

National Institute on Deafness and Other Communication Disorders (NIDCD)

Chief Medical Officer

MD, MPH, MS

Debara L. Tucci

National Institute on Deafness and Other Communication Disorders (NIDCD)

Chief Executive Officer since 2019

MD, MS, MBA

Findings from Research

In a study of 277 adults treated with cisplatin for head and neck cancer, those taking atorvastatin experienced significantly less hearing loss (9.7%) compared to nonstatin users (29.4%), indicating atorvastatin's protective effect against cisplatin-induced ototoxicity.

Atorvastatin users were found to be 53% less likely to develop significant hearing loss from cisplatin, with no difference in three-year survival rates between atorvastatin and nonstatin users, suggesting atorvastatin's efficacy in preserving hearing without compromising cancer treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atorvastatin is associated with reduced cisplatin-induced hearing loss. Fernandez, KA., Allen, P., Campbell, M., et al.[2021]

This systematic review and meta-analysis evaluated the protective effects of metformin, statins, and anti-inflammatory drugs on head and neck cancer, highlighting their potential roles in cancer prevention.

The findings suggest that these medications may offer beneficial effects in reducing the risk or severity of head and neck cancer, although specific efficacy details and mechanisms were not provided in the abstract.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Limited Evidence Suggests Metformin Might Be Beneficial to Reduce Head and Neck Cancer Risk and Increase Overall Survival, While Any Benefit With Antiinflammatory Drugs Is Inconsistent. Veitz-Keenan, A., Silvestre Calle, TD., Bergamini, M.[2020]

Head and neck cancer (HNC) patients with hyperlipidemia who were taking statins showed significantly better overall survival (73.0%) and cancer-specific survival (81.2%) compared to those not taking statins (61.7% overall survival and 69.2% cancer-specific survival) and those without hyperlipidemia (58.6% overall survival and 69.1% cancer-specific survival).

Statin use in HNC patients was associated with improved survival outcomes even after controlling for various factors, indicating that statins may serve as a beneficial adjunct treatment in managing head and neck cancer, with no significant difference in toxicity-related events among the groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Statin use associated with improved overall and cancer specific survival in patients with head and neck cancer. Gupta, A., Stokes, W., Eguchi, M., et al.[2020]

Lovastatin has been shown to significantly reduce cisplatin-induced hearing loss in adult mice, suggesting its potential as a protective agent against ototoxicity caused by cisplatin treatment.

The protective effect of lovastatin was found to be more pronounced in female mice, indicating that sex differences may influence the required dosage for effective protection, which is important for future clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lovastatin protects against cisplatin-induced hearing loss in mice. Fernandez, K., Spielbauer, KK., Rusheen, A., et al.[2021]

In a study of 4669 head and neck cancer patients, those who used statins showed a trend towards reduced recurrence rates at 3 and 5 years compared to matched controls, with risk ratios of 0.79 and 0.89, respectively.

However, the association was not statistically significant, indicating that while there may be a potential benefit of statin use in reducing HNC recurrence, further research is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of statin use on head and neck cancer prognosis in a multicenter study using a Common Data Model. Seol, S., Choi, JR., Choi, B., et al.[2023]

Ototoxicity, which can lead to irreversible hearing loss, affects 30-40% of patients undergoing radiotherapy for head and neck cancer, highlighting the need for effective prevention strategies.

Primary prevention measures include limiting radiation doses to the cochlea and considering alternative chemotherapy options like carboplatin or cetuximab to reduce the risk of hearing loss, along with monitoring and evaluating individual risk factors before treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ototoxicity in head and neck cancers after radiotherapy and chemoradiotherapy: From primary prevention to tertiary prevention]. Espenel, S., Garcia, MA., Guy, JB., et al.[2017]

In a study of 97,252 head and neck cancer patients, those on statin medication had a significantly higher five-year survival rate of 75.19% compared to 70.48% for those not on statins.

Statin use was associated with a reduced risk of death, with a hazard ratio of 0.80, suggesting that statins may improve overall survival in head and neck cancer patients, although the study's retrospective nature means results should be interpreted cautiously.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Statin Medication Improves Five-Year Survival Rates in Patients with Head and Neck Cancer: A Retrospective Case-Control Study of about 100,000 Patients. Wüster, J., Heiland, M., Nahles, S., et al.[2023]

Statin drugs, commonly used for lowering cholesterol, may improve survival rates and reduce treatment-related toxicities in patients with head and neck squamous cell carcinoma (HNSCC), based on a review of preclinical and clinical studies.

Due to their affordability and safety profile, statins are suggested as a promising adjunctive therapy in HNSCC treatment, warranting further research to understand their mechanisms and enhance patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repurposing Statin Drugs to Decrease Toxicity and Improve Survival Outcomes in Head and Neck Cancer. Bourguillon, RO., Stokes, WA., Dorth, J., et al.[2022]

References

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

Atorvastatin is associated with reduced cisplatin-induced hearing loss. [2021]

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

Limited Evidence Suggests Metformin Might Be Beneficial to Reduce Head and Neck Cancer Risk and Increase Overall Survival, While Any Benefit With Antiinflammatory Drugs Is Inconsistent. [2020]

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

Statin use associated with improved overall and cancer specific survival in patients with head and neck cancer. [2020]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Lovastatin protects against cisplatin-induced hearing loss in mice. [2021]

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

Effect of statin use on head and neck cancer prognosis in a multicenter study using a Common Data Model. [2023]

6. France pubmed.ncbi.nlm.nih.gov

[Ototoxicity in head and neck cancers after radiotherapy and chemoradiotherapy: From primary prevention to tertiary prevention]. [2017]

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

Statin Medication Improves Five-Year Survival Rates in Patients with Head and Neck Cancer: A Retrospective Case-Control Study of about 100,000 Patients. [2023]

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

Repurposing Statin Drugs to Decrease Toxicity and Improve Survival Outcomes in Head and Neck Cancer. [2022]