Cryotherapy vs 5-Fluorouracil for Actinic Keratosis

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of California, Davis

Must not be taking: Systemic retinoids

Disqualifiers: Cognitive impairment, Incarceration, Immuno-compromised, 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

Compensation: Varies

Number of Visits: 3

Duration: 6 weeks

73 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The goal of this clinical trial is to compare the effectiveness and safety of two treatments-cryotherapy and 5-Fluorouracil (5-FU)-for actinic keratosis, a common skin condition caused by long-term sun exposure. Cryotherapy is a treatment that uses extreme cold produced by liquid nitrogen to freeze and destroy abnormal cells, and 5-FU is a topical cream applied to the skin to treat lesions by interfering with cell growth. The main questions this trial aims to answer are: * Which treatment, cryotherapy or 5-FU, is more effective in reducing the number of actinic keratosis lesions? * What are the side effects associated with each treatment? * How do these treatments impact patient satisfaction, cosmetic outcomes, and health-related quality of life? Participants will: * Undergo a baseline assessment where their demographics information such as age, sex, race, smoking status, and medical history are recorded, along with the number and severity of actinic keratosis lesions. * Receive both cryotherapy and 5-FU, with each treatment applied to different areas of their body. The area of the body to receive each treatment is decided by a random process (like flipping a coin). * Complete weekly surveys to monitor for side effects during and after the treatment period. * Return to the clinic for follow-up assessments at 3 months and 12 months.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you have used systemic retinoids in the past 3 months, you cannot participate.

Is the combination of cryotherapy and 5-fluorouracil safe for treating actinic keratosis?

The combination of cryotherapy and 5-fluorouracil (5-FU) is generally safe for treating actinic keratosis, with no serious adverse events reported. However, local skin reactions like redness and irritation are common but usually temporary. ^{1 2 3 4 5}

How does the treatment of actinic keratosis with cryotherapy and 5-fluorouracil differ from other treatments?

The combination of cryotherapy and 5-fluorouracil (5-FU) is unique because it allows for both targeted and generalized treatment of actinic keratosis (AK), effectively clearing multiple lesions while potentially reducing side effects compared to using cryotherapy alone. This approach is beneficial for patients with numerous AKs, as 5-FU can treat larger areas, and the combination has shown promise in improving clearance rates and tolerability. ^{1 3 6 7 8}

What data supports the effectiveness of the treatment for actinic keratosis?

Research shows that using cryotherapy combined with 5-fluorouracil cream can effectively clear actinic keratosis lesions for up to 2 months, with fewer side effects compared to cryotherapy alone. Additionally, 5-fluorouracil cream has been shown to be a cost-effective way to manage multiple facial actinic keratosis lesions. ^{1 3 6 9 10}

Who Is on the Research Team?

Daniel Eisen, MD

Principal Investigator

UC Davis Department of Dermatology

Are You a Good Fit for This Trial?

This trial is for individuals with actinic keratosis, a skin condition from long-term sun exposure. Participants will have their demographics and medical history recorded and must be willing to receive both cryotherapy and 5-Fluorouracil on different body areas, complete weekly surveys, and return for follow-ups.

Inclusion Criteria

Able to give informed consent themselves

Willing to return for follow up visits

I have been diagnosed with 10 or more AKs on my head, neck, or limbs.

Exclusion Criteria

Immuno-comprised status

Allergy to trial drugs or peanut/soy products

Incarcerated

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo a baseline assessment where demographics and medical history are recorded, along with the number and severity of actinic keratosis lesions

1 week

1 visit (in-person)

Treatment

Participants receive both cryotherapy and 5-FU, with each treatment applied to different areas of their body

6 weeks

Weekly surveys (virtual)

Follow-up

Participants return to the clinic for follow-up assessments at 3 months and 12 months to monitor for side effects and evaluate treatment outcomes

12 months

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• 5-Fluorouracil
• Cryotherapy

Trial Overview The trial compares the effectiveness of cryotherapy (freezing abnormal cells) versus 5-Fluorouracil cream (interfering with cell growth) in treating actinic keratosis. It assesses which reduces lesions better and evaluates side effects, patient satisfaction, cosmetic outcomes, and quality of life.

How Is the Trial Designed?

Group I: Cryotherapy and 5-Fluoruracil Experimental Treatment 2 Interventions

Each actinic keratosis lesion, or treatment area, will be randomly assigned to receive either cryotherapy or 5-fluoruracil treatment.

5-Fluorouracil is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as 5-FU for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer
• Ovarian cancer

Approved in United States as 5-FU for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer

Approved in Canada as 5-FU for:

• Colorectal cancer
• Breast cancer
• Stomach cancer

Approved in Japan as 5-FU for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer

Who Is Running the Clinical Trial?

University of California, Davis

Lead Sponsor

Trials

958

Recruited

4,816,000+

Published Research Related to This Trial

A 63-year-old man developed a seborrheic dermatitis-like reaction on his face after using topical 5-fluorouracil on his arms for 7 days, indicating that distant skin reactions can occur with this medication.

The facial dermatitis resolved after stopping the treatment and recurred upon reapplication, confirming a direct link between the drug and the adverse effect, although the exact mechanism behind this distant reaction remains unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical Application of 5-Fluorouracil Associated with Distant Seborrheic Dermatitis-like Eruption: Case Report and Review of Seborrheic Dermatitis Cutaneous Reactions after Systemic or Topical Treatment with 5-Fluorouracil. Werbel, T., Cohen, PR.[2020]

Citations

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

Efficacy of cryosurgery and 5-fluorouracil cream 0.5% combination therapy for the treatment of actinic keratosis. [2014]

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

One-week treatment with 0.5% fluorouracil cream prior to cryosurgery in patients with actinic keratoses: a double-blind, vehicle-controlled, long-term study. [2013]

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

The management of actinic keratoses in the United States with topical fluorouracil: a pharmacoeconomic evaluation. [2013]

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

Topical treatment of actinic keratosis with fluorouracil: is irritation associated with efficacy? [2013]

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

Treatment-refractory actinic keratoses successfully treated using simultaneous combination topical 5-fluorouracil cream and imiquimod cream: a case-control study. [2018]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Topical Application of 5-Fluorouracil Associated with Distant Seborrheic Dermatitis-like Eruption: Case Report and Review of Seborrheic Dermatitis Cutaneous Reactions after Systemic or Topical Treatment with 5-Fluorouracil. [2020]

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

Severity of Local Skin Reactions with 4% 5-Fluorouracil Plus Emollient versus 4% 5-Fluorouracil Alone in Patients with Actinic Keratosis: A Single-Blind Randomised Trial. [2023]

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

Does intermittent "pulse" topical 5-fluorouracil therapy allow destruction of actinic keratoses without significant inflammation? [2019]

9. England pubmed.ncbi.nlm.nih.gov

Comparison of topical 5-fluorouracil formulations in actinic keratosis treatment. [2013]

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

Practice trends in the treatment of actinic keratosis in the United States: 0.5% fluorouracil and combination cryotherapy plus fluorouracil are underused despite evidence of benefit. [2017]