Actinic Keratoses
Conditions
Keywords
5-Fluorouracil, Calcipotriol
Brief summary
5-Fluorouracil (5FU) is proven to be the most effective therapy in field directed treatment for AK, with Jansen et al. reporting a 1-year probability of treatment success of 74.7%. However, treatment with 5FU is associated with side effects, like erythema, itching, a burning sensation and crusting, and a burdensome dosing regimen of twice daily application for four weeks. This long treatment duration in combination with side-effects and overall lifestyle adjustments during treatment can be the reason for poor adherence and premature termination, and it can also lead to future refusal of 5FU therapy. Therefore, room for improvement lies in increasing the tolerability, in terms of side effects or treatment duration, while maintaining the efficacy of 5FU in the treatment of AK. Addition therapy, which can shorten the duration of treatment, might be the key to success. Calcipotriol (CAL) enhances thymic stromal lymphopoietin (TSLP), an epithelium-derived cytokine, which promotes antitumor immunity. Therefore, it is known to have a synergistic effect when combined with 5FU in the treatment of AK. This suggests that short-term treatment with 5FU-CAL is effective and provides the opportunity to shorten duration of treatment, thereby improving tolerability of treatment and full adherence to the treatment regimen. However, no study compared 5FU-CAL combination therapy with standard 5FU treatment for a duration of 28 days. This study aims to evaluate whether a short course of combination therapy with 5FU-CAL is non-inferior to a full course of 5FU monotherapy with respect to the 1-year probability of treatment success.
Interventions
DRUG5FU-Calcipotriol
topical 5FU-CAL, twice daily, during 4 or 6 consecutive days, depending on the treatment location
DRUG5-FU 50 MG/ML Topical Cream
topical 5FU, twice daily, 7 days a week, during 4 weeks
Sponsors
Maastricht University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Masking description
The investigator, who is also a physician and will evaluate treatment effect, is blinded to the allocated treatment
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults above 18 years of age * Clinical and dermoscopical diagnosis of AK by a dermatologist, in one or more area(s): * Face, ears, (balding) scalp * Neck/Shawl area, including the sun-exposed chest area * Upper extremities * Number of AK lesions ≥4 in a continuous treatment area of up to 100 cm2 * AK Olsen grade I-III
Exclusion criteria
* Previous field treatment for AK within 2cm of the treatment area, within 3 months * (non) melanoma skin cancer in treatment area * Mucosal lesions * Genetic skin cancer disorder * Women who are pregnant or breastfeeding * Women of childbearing potential, who are not willing to use effective contraceptive measures * Previous allergy or intolerance to either 5FU or calcipotriol * Patients with known contra-indications for calcipotriol use: previous diagnosis of hyper-calcemia, disturbed calcium metabolism, severe kidney or liver dysfunction * Concurrent use of oral capecitabine or any other topical or systemic chemopreventive agent for any indication * Concurrent use of other topical treatments registered as treatment for AK * Limited understanding of the Dutch language and not being able to give informed consent (incapacitated patients)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment success at 12 months post-treatment | 12 months after finishing treatment | Treatment success at 12 months post treatment, defined as ≥75% reduction in the number of AK lesions in the treatment area (partial clearance) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AK clearance rate | 3 and 12 months after finishing treatment | mean percentage change in AK lesions at 3 and 12 months post-treatment |
| Recurrence rate | 3 and 12 months after finishing treatment | New lesions and need for retreatment at 3 and 12 months post-treatment |
| Adverse effects | During treatment and 3 months post-treatment | Patients experiencing moderate to severe adverse effects |
| Patient satisfaction | 3 and 12 months post-treatment | Patients who express to be satisfied with their treatment |
| Quality of life before, during and after treatment | Baseline, 1 week after finishing treatment and 3 and 12 months post-treatment | The mean score for quality of life on the Skindex-17 questionnaire. The Skindex-17 questionnaire has 17 items investigating the quality of life on different domains. The questions are answered on a five-point scale. A higher score represents a higher impact on QoL. |
| Treatment compliance | During treatment | Patients who are fully compliant to the prescribed treatment regimen (5FU-CAL or 5FU monotherapy) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Long-term risk for cSCC | at least 3 years post-treatment | The long-term probability of developing a cSCC |
Countries
Netherlands
Contacts
Primary ContactMyrthe MG Moermans, MD
Outcome results
None listed