5fluorouracil for Advanced Photoaging

Phase III Comparative Study About the Use of 5% 5-fluorouracil Cream Versus Its Utilization as Agent for Sequential Superficial Peeling in the Treatment of Advanced Photoaging

It is well known the efficacy of 5% 5-fluoruracil for multiple and superficial actinic keratosis (AKs)treatment. Recently its additional benefit for advanced and severe photoaging while treating Aks was reported.

The aim of this study is to compare the efficacy and safety of the two modalities of 5% 5-FU use for forearms photoaging.

Study Overview

• Status: Unknown
• Conditions: Actinic Keratosis; Photoaging
• Intervention / Treatment: Drug: 5-fluoruracil; Procedure: 5-fluoruracil

Detailed Description

The use of 5% 5-fluorouracil (5-FU) cream, twice a day, during 3 weeks represents a classic treatment for multiple and superficial AKs. The main adverse event is the severe skin irritation leading to interruption of the treatment in some cases. In the last decade a superficial pulse-peeling using it as agent in sequential applications was described. This modality of treatment has been demonstrated efficacy and better tolerability.

The improvement of the overall aspect of photodamaged skin is observed while treating multiple AKs.

There are no comparative study between the two types of 5% 5-FU use. So that is the purpose of our clinical trial.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • SP
    • Sao Paulo, SP, Brazil, 04075-000
      • Recruiting
      • Edileia Bagatin
      • Contact: Carolina Zerbini, MD; Phone Number: 55-15-97280079; Email: carolzerbini@hotmail.com
      • Principal Investigator: Carolina Zerbini, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 46 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy Men and women, aged from 50 to 75 anos;
2. Phototype I a III (Fitzpatrick Classification);
3. Advanced photoaging on forearms, with multiple superficial actinic keratosis;
4. Agreement with no sun exposure during the study and
5. Agreement with study conditions,capacity to understand and follow the orientations and form consent signature.

Exclusion Criteria:

1. Topical treatment with:

   • tretinoin in the last 6 months ;
   • other retinoids, alpha-hydroxyacids, poli-hydroxyacids, beta-hydroxyacids and ascorbic acid in the last 3 months;
2. Treatment by chemical peeling, microdermabrasion and non-ablative laser in the last 3 months;
3. Treatment with systemic retinoid in the last 6 months ;
4. Chemotherapy in the last 3 months;
5. Hypersensibility to parabens;
6. Infectious or inflammatory dermatosis on forearms;
7. Clinical evidence of immunosuppression and
8. Presence of photodermatosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 5% 5-fluoruracil cream; 30 patients will use 5% 5-fluoruracil cream, twice a day, during 3 weeks, in one randomized forearm	Drug: 5-fluoruracil; 5% 5-fluoruracil cream, twice a day, during 3 weeks; Other Names: Topical treatment
Active Comparator: 5% 5-fluoruracil peeling; The same 30 patients will be submitted to 4 applications of 5% 5-fluoruracil superficial peeling in the other forearm	Procedure: 5-fluoruracil; The same 30 patients will be submitted to 4 weekly application of superficial peeling using 5% 5-fluoruracil in propyleneglycol as vehicle. The applications will be performed by physician (one of the co-investigators); Other Names: Cosmetic procedure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Photographic Evaluation	Photographic blinded evaluation by two independent observers, comparing modifications of forearms skin overall aspect before and after 60 and 180 days of the treatments. The following 5 point scale will be used: -2=much worse; -1=worse; 0=inlatered; 1=better, 2= much better	0, 60, 180 days
Change in Microscopic Evaluation	Skin biopsies will be performed and coloration by hematoxilin-eosin, Verhoeff, Tricromio Masson , Picrosirius and biomarkers (p53, bcl2, collagen 1)will be used. The modifications on corneal layer and epidermal thickness, dermal elastotic material and collagen deposition and biomarkers expression will be evaluated by digital quantitative analysis, comparing the findings before (day 0) and after (day 180)treatments.	0, 180 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inflammatory Skin Reaction	Comparison between treatments on inflammatory skin reaction will be performed by expression of interleucin-1, using immunohistochemistry	30 day
Occurence and Evaluation of Adverse Events	Predictable and unpredictable side effects and their intensity related by patient and/or observed by investigator will be analized and compared between the treatments	30, 60, 180 days
Change in Patient Opinion	Patient opinion concerning modification on forearms skin overall aspect, using a 5 point scale: -2=much worse; -1=worse; 0=inaltered; 1=better, 2= much better, comparing day 0 to 60, 60 to 180 and 0 to 180.	0, 30, 60, 180 days
Change in Investigator Clinical Evaluation	Investigator efficacy evaluation through actinic keratosis counting, on days 0, 30, 60 and 180 as weel as modification on forearms skin overall aspect. That will be performed by comparision of skin examination on days 60 and 180 to photography captured on days 0 and 60, i.e, 0 to 60, 60 to 180 and 0 to 180, using a 5 point scale: -2=much worse; -1=worse; 0=inaltered; 1=better, 2= much better	0, 30, 60, 180 days
Change in Forearm Photoaging Classification	A classification will be created and validated by investigators and five independent observers previously to classify forearm photoaging. After validation it will be applied to study subjects on days 0, 60 and 180 to evaluate modification on the forearm photoaging grade for each tretament.	0, 60, 180 days

Collaborators and Investigators

• Sponsor: Federal University of São Paulo
• Investigators: Study Chair: Ediléia Bagatin, PhD, PROFESSOR

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Anticipated): September 1, 2011
• Study Completion (Anticipated): March 1, 2012

Study Registration Dates

• First Submitted: July 5, 2011
• First Submitted That Met QC Criteria: July 28, 2011
• First Posted (Estimate): July 29, 2011

Study Record Updates

• Last Update Posted (Estimate): July 29, 2011
• Last Update Submitted That Met QC Criteria: July 28, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Keywords: Carcinogenesis; Actinic keratosis; Photoaging; 5-fluoruracil
• Additional Relevant MeSH Terms: Neoplasms; Precancerous Conditions; Keratosis, Actinic; Keratosis; Skin Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Fluorouracil
• Other Study ID Numbers: Carol2011