Oral Isotretinoin Versus Topical Tretinoin for Actinic Keratosis
Condition: Actinic Keratosis
MeSH terms: Keratosis, Actinic; Keratosis
Study type: Interventional
Phase: Phase 2

Summary: 
      Actinic keratosis (AKs) are premalignant disorders that can evolve into skin cancer. To
      prevent their development, a study is being conducted with oral isotretinoin and topical
      tretinoin to verify what drug is the most effective and has the best security profile for
      these patients. Along with these treatments, cryotherapy with liquid nitrogen and sunscreens
      will be part of the treatment. The study will have the duration of 10 months. In the first
      four months, the AKs will be counted and treated with cryotherapy (face and arms) and
      sunscreens FPS 60 will be used. After it, the patients will return (the AKs will be counted),
      a new session of cryotherapy will be performed and they will be randomized into two groups:
      one group using oral isotretinoin 10mg/day ( ISO: 30 patients) and the other one using
      tretinoin 0,05% cream (AR: 30 patients) applied on face and arms. Skin biopsies will be done
      for all 60 patients at the beginning of the treatment with retinoids (isotretinoin and
      tretinoin). After six months of treatment with retinoids, the study will be stopped, AKs will
      be counted again and skin biopsies will be done. Patients in the group ISO (oral
      isotretinoin) also have to make blood tests at the beginning, two months and after six months
      of the treatment. Clinical (AK counting), histological (improvement of parts of the skin) and
      immunohistochemical parameters will be evaluated to see what drug is more effective for
      prevention of AKs.
    

Detailed description: 
      This study is a randomized controlled trial with 60 men and women (already in menopause for
      at least one year), aged 50-75 years. At the beginning, the number of actinic keratosis (AKs)
      of face and forearms will be counted and treated with cryotherapy with liquid nitrogen
      (LN).The patients will be randomized in two groups: one receiving oral isotretinoin 10mg/day
      every day and other receiving tretinoin 0,05% cream applied in the face and arms every other
      night, for six months. Along with these treatments, patients will use sunscreens FPS 60 with
      UVA and UVB protection. The inclusion criteria will be the presence of at least 10 and
      maximum 40 AKs (visible or palpable). Skin biopsies will be performed twice (before and after
      treatment with retinoids) for all patients, in the left forearm at a standardized site.
      Histological and immunohistochemical with blinded- evaluator analysis will be done. The main
      objective of the study is to evaluate clinical, histological and immunohistochemical effects
      of retinoids for AK prevention on face and forearms of immunocompetent individuals. Efficacy
      evaluation will be measured by improving clinical (AK counting before and after treatments),
      histopathological (Hematoxilin-eosin and Verhoeff staining) and immunohistochemical
      parameters (markers for carcinogenesis - p53 protein, Bcl-2 and Bax). The secondary objective
      is evaluate the tolerability and safety of the drugs and their impact in quality of life. The
      safety analysis will be related to adverse events of the two drugs and the blood tests will
      be performed in the ISO group patients. Indirectly, by decreasing the number of AKs and the
      expression of cutaneous carcinogenesis markers, a decrease in the risk of squamous cell
      carcinoma could be infered . This principle is used by many drugs called chemoprophylactic
      drugs, and the retinoids are considered in this group.
    

Intervention name(s): Oral isotretinoin; Tretinoin 0,05% cream; Sunscreen FPS 60
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Oral isotretinoin - 10mg/day (one pill) after lunch for six months; Topical tretinoin 0,05% cream - applied every other night in the face and forearms for six months; Sunscreen FPS 60 applied on sun exposed areas every 3 hours daily
Other intervention name(s): Acnova; Vitacid 0,05% cream; Skin Block 60 Fluide Extreme
Intervention MeSH terms: Tretinoin; Isotretinoin; Sunscreening Agents
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: actinic keratosis; tretinoin; isotretinoin; cryotherapy; sun protection factor; clinical clearance