Randomized, Vehicle-Controlled Trials of Topical 5-Fluorouracil Therapy for Actinic Keratosis Treatment: An Overview

Rahvar, Maral; Lamel, Sonia A.; Maibach, Howard I.

doi:10.2217/imt.12.93

Cited by 16 publications

(14 citation statements)

References 26 publications

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“…In 2012, Rhavar et al [61] performed a systematic review of 103 studies into the efficacy of 0.5% 5-FU. Only four studies were found to be suitable randomized vehicle-controlled trials.…”

Section: Discussionmentioning

confidence: 99%

Actinic Keratosis: Rationale and Management

Dodds

Chia

Shumack

2014

Dermatol Ther (Heidelb)

105

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Actinic keratoses (AKs) are common skin lesions heralding an increased risk of developing squamous cell carcinoma (SCC) and other skin malignancies, arising principally due to excessive ultraviolet (UV) exposure. They are predominantly found in fair-skinned individuals, and increasingly, are a problem of the immunosuppressed. AKs may regress spontaneously, remain stable or transform to invasive SCC. The risk of SCC increases for those with more than 5 AKs, and the majority of SCCs arise from AKs. The main mechanisms of AK formation are inflammation, oxidative stress, immunosuppression, impaired apoptosis, mutagenesis, dysregulation of cell growth and proliferation, and tissue remodeling. Human papilloma virus has also been implicated in the formation of some AKs. Understanding these mechanisms guides the rationale behind the current available treatments for AKs. One of the main principles underpinning the management of AKs is that of field cancerization. Wide areas of skin are exposed to increasing amounts of UV light and other environmental insults as we age. This is especially true for the head, neck and forearms. These insults do not target only the skin where individual lesions develop, but also large areas where crops of AKs may appear. The skin between lesions is exposed to the same insults and is likely to contain as-yet undetectable preclinical lesions or areas of dysplastic cells. The whole affected area is known as the ‘field’. Management is therefore divided into lesion-directed and field-directed therapies. Current therapies include lesion-directed cryotherapy and/or excision, and topical field-directed creams: 5-fluorouracil, imiquimod, diclofenac, photodynamic therapy and ingenol mebutate. Combining lesion- and field-directed therapies has yielded good results and several novel therapies are under investigation. Treatment is variable and tailored to the individual making a gold standard management algorithm difficult to design. This literature review article aims to describe the rationale behind the best available therapies for AKs in light of current understanding of pathophysiology and epidemiology. A PubMed and MEDLINE search of literature was performed between January 1, 2000 and September 18, 2013. Where appropriate, articles published prior to this have been referenced. This is not a systematic review or meta-analysis, but aims to highlight the most up to date understanding of AK disease and its management.Electronic supplementary materialThe online version of this article (doi:10.1007/s13555-014-0049-y) contains supplementary material, which is available to authorized users.

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“…In 2012, Rhavar et al [61] performed a systematic review of 103 studies into the efficacy of 0.5% 5-FU. Only four studies were found to be suitable randomized vehicle-controlled trials.…”

Section: Discussionmentioning

confidence: 99%

Actinic Keratosis: Rationale and Management

Dodds

Chia

Shumack

2014

Dermatol Ther (Heidelb)

105

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“…The recurrence rate ranged from 10 to 25%. Actinic keratosis (sun-induced dysplasia) of the lip vermilion can be treated successfully with topical 5-fluorouracil (5-FU) twice a day for 2 to 4 weeks (2 vs 5% cream) or with topical imiquimod 5% cream 2 to 3 times per week for up to 4 months 100,101 (Fig 13). Results are more consistent with 5-FU.…”

Section: Managementmentioning

confidence: 99%

Leukoplakia—A Diagnostic and Management Algorithm

Villa

Woo

2017

Journal of Oral and Maxillofacial Surgery

101

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Oral white lesions are frequently encountered in daily practice. Most white lesions are benign (eg, reactive keratoses or keratoses from inflammatory conditions) and the diagnosis is usually evident from the clinical presentation and histopathology. Leukoplakia is a common condition characterized by an increased risk for malignant transformation. Histopathology of leukoplakia can disclose hyperkeratosis with dysplasia or carcinoma or hyperkeratosis or parakeratosis without dysplasia. Treatment depends on demographic, social, clinical, and histopathologic factors. This review focuses on the diagnosis and management of oral leukoplakia.

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“…This transformation can be attributed to ultraviolet-induced mutation of the p53 gene and subsequent clonal proliferation of squamous cells in the epidermis. 3 , 4 Mutations in p53 are seen in approximately 53% of AKs and 70% to 90% of squamous cell carcinomas, and the progression of AKs to squamous cell carcinomas is estimated at 0.1% to 10%. 2 , 4 Hence, the treatment of all AKs is recommended and considered an important step in preventative dermatology.…”

Section: Introductionmentioning

confidence: 99%

“…Topical 5-FU is an antineoplastic medication that has been used to treat AKs since the 1970s when it was first approved by the Food and Drug Administration for topical dermatologic use. 3 It is a pyrimidine analog that irreversibly binds and inhibits thymidylate synthetase and leads to a reduction in DNA and RNA synthesis. 3 It preferentially targets AKs over normal epidermis.…”

Section: Introductionmentioning

confidence: 99%

“… 3 It is a pyrimidine analog that irreversibly binds and inhibits thymidylate synthetase and leads to a reduction in DNA and RNA synthesis. 3 It preferentially targets AKs over normal epidermis. Topical 5-FU can cause an erosive dermatitis, pain, pruritus, hypopigmentation, and hyperpigmentation, which can result in poor medication compliance.…”

Section: Introductionmentioning

confidence: 99%

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