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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines two treatments, cryotherapy and 5-Fluorouracil (5-FU), to determine which is more effective for actinic keratosis, a skin condition caused by excessive sun exposure. Cryotherapy uses extreme cold to freeze and remove damaged cells, while 5-FU is a cream that inhibits the growth of these cells. The researchers aim to identify which treatment better reduces skin spots, their side effects, and their impact on patients' perceptions of their skin and quality of life. This trial suits individuals with 10 or more actinic keratosis spots on their head, neck, or limbs. Participants will apply both treatments to different body areas to compare results. As a Phase 4 trial, the treatments are already FDA-approved and proven effective, providing insight into their benefits for more patients.

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.

What is the safety track record for cryotherapy and 5-Fluorouracil?

A previous study found that a cream with 4% 5-fluorouracil (5-FU) was both effective and safe for people with actinic keratosis. This cream effectively reduced skin lesions and was generally easy for users to tolerate. Some experienced side effects, such as skin irritation, but these were usually mild.

Research has also shown that cryotherapy is a well-tolerated option for treating actinic keratosis. This treatment uses extreme cold to freeze and remove abnormal skin cells. Most people manage the treatment well, although some might feel discomfort or notice changes in their skin afterward.

Both treatments have been used for a long time and have good safety records. Patients should still monitor their condition during treatment and report any issues to their doctor. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Most treatments for actinic keratosis, like cryotherapy, involve freezing the lesions, which can be painful and may require recovery time. However, 5-Fluorouracil offers a different approach by using a topical cream that specifically targets and disrupts abnormal cell growth. This method can be less invasive and allows for treatment of larger areas at once. Researchers are excited about the potential for 5-Fluorouracil to provide a more comfortable and effective alternative to traditional treatments, with the added benefit of treating multiple lesions simultaneously.

What evidence suggests that this trial's treatments could be effective for actinic keratosis?

This trial will compare the effectiveness of cryotherapy and 5-Fluorouracil (5-FU) in treating actinic keratosis, a skin condition caused by sun damage. Research has shown that both treatments are effective. Cryotherapy can cure up to 98.8% of cases by using extreme cold to freeze and destroy abnormal skin cells. Meanwhile, 5-FU cream significantly reduces the number of lesions; one study reported a 62.4% reduction after just one week of use. The treatments work differently: cryotherapy provides quick results, while 5-FU offers a more gradual approach. Participants in this trial will receive either cryotherapy or 5-FU for their lesions. ^{1 6 7 8 9}

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

Incarcerated

Allergy to trial drugs or peanut/soy products

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10680462/

Evaluating the Efficacy and Safety of 4% 5-Fluorouracil ... Treatment with 4% 5-fluorouracil cream was highly efficacious, safe, and prevented disease recurrence in approximately 27% of patients who achieved complete ...

2. medicaljournalssweden.se medicaljournalssweden.se/actadv/article/view/11954

Evaluating the Efficacy and Safety of 4% 5-Fluorouracil ... This narrative review discusses data on 4% 5-fluorouracil cream to treat actinic keratosis, and provides the authors' expert opinion on issues ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S157210002400108X

Pre-treatment with topical 5-fluorouracil increases the ... Twelve weeks after treatment 87 % of all AKs cleared after 5-FU+dPDT compared to 74 % after dPDT alone (p<0.0001). For grade II AKs, the lesion response rate ...

4. jamanetwork.com jamanetwork.com/journals/jamadermatology/fullarticle/480680

Effect of a 1-Week Treatment With 0.5% Topical ... Results At 4 weeks, mean actinic keratosis lesion count was reduced by 62.4% in the 0.5% fluorouracil group vs 28.8% in the vehicle group (P<.001), and complete ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11499312/

Calcipotriol and 5-Fluorouracil Combination Therapy for ... The combination of 5-FU and calcipotriol effectively treats actinic keratosis by enhancing the immune response and targeting cell overgrowth.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37982726/

Evaluating the Efficacy and Safety of 4% 5-Fluorouracil ... This narrative review discusses data on 4% 5-fluorouracil cream to treat actinic keratosis, and provides the authors' expert opinion on issues ...

7. mayoclinic.org mayoclinic.org/drugs-supplements/fluorouracil-topical-route/description/drg-20063877

Fluorouracil (topical route) - Side effects & dosage Fluorouracil topical is used to treat actinic or solar keratoses and a type of skin cancer called superficial basal cell carcinoma.

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/016831Orig1s063lbl.pdf

EFUDEX® (fluorouracil) TOPICAL SOLUTIONS AND CREAM ... Actinic or Solar Keratosis: Apply cream or solution twice daily in an amount sufficient to cover the lesions. Medication should be continued ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0149291802800121

Evaluation of the efficacy and tolerability of 0.5% ... Results: Treatment with 0.5% fluorouracil cream reduced the number of AK lesions from 11.3 at baseline to 2.5 at the end of the 4-week follow-up phase, compared ...