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American Journal of Cancer

, Volume 2, Issue 3, pp 151–168 | Cite as

New Approaches to the Treatment of Actinic Keratosis

Leading Article

Abstract

Actinic keratoses are hyperkeratotic skin lesions that represent focal abnormal proliferation of epidermal keratinocytes. The major cause of actinic keratoses in otherwise healthy Caucasians appears to be exposure to the sun. Since they are commonly associated with squamous cell carcinoma (SCC) of photodamaged skin, therapy and prevention of these actinic keratoses are important steps to decrease the occurrence of SCC.

New approaches to prevention include new advances in sunscreen that can block ultraviolet-A (UVA) rays more effectively. The major new advance in this regard is the use of microfine zinc oxide in sunscreens.

Photodynamic therapy of actinic keratoses can now be done by first applying an aminolevulinic acid (ALA) solution to the site, followed 14–18 hours later by photoactivation using a fluorescent blue light source. ALA is a pro-drug that is not photoactive; it is converted in the actinic keratosis to protoporphyrin disodium, which is the photoactive form of the drug. The complete response rate (complete clearing of actinic keratoses, evaluated individually) was 84% with ALA photodynamic therapy (ALA-PDT).

A topical 3% diclofenac gel (Solaraze™) is US FDA approved to treat actinic keratoses; it has a maximum complete response rate of about 47%. In addition, a topical 5% imiquimod cream (Aldara™) is also being used to treat actinic keratoses (off-label use), with complete clearing response rates of 40–87%.

A 0.5% fluorouracil cream product in a new microsponge delivery system (Carac®) has been approved by the US FDA for treatment of actinic keratoses of the face and scalp. This product is approved for once daily application and completely clears 48% of target actinic keratoses. The marketing of the fluorouracil cream suggests that since only l/40th as much fluorouracil is absorbed systemically, it is theoretically safer for treatment of actinic keratoses and may minimize adverse reactions that could occur in patients with dihydropyrimidine dehydrogenase (DPD) deficiency.

In this review we re-evaluate the status of studies using the older 2–5% fluorouracil (Efudex®) products to treat actinic keratoses as well as do a postmarketing review of adverse reactions with these older, well established products. The limited studies available suggest a complete response rate of 75–86% with 2–5% Efudex®. A postmarketing evaluation of 31 years of adverse drug reaction reports is presented, which demonstrates that the incidence of severe systemic reactions is very low and in the range of 1 in 1 949 288 prescriptions (seven cases in 31 years). A relationship between DPD deficiency and severe systemic toxicity is not suggested by these postmarketing adverse drug reaction data. Furthermore, recent studies in cancer patients suggest that DPD deficiency does not by itself explain severe reactions to systemically administered fluorouracil. A detailed comparison of Carac® and Efudex® is presented.

Keywords

Complete Response Rate Imiquimod Actinic Keratosis Actinic Keratosis Lesion Photodamaged Skin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

Dr Jeffes is a consultant for ICM Pharm and has done contract work for them. ICN provided funding to support the production of this review.

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Copyright information

© Adis Data Information BV 2003

Authors and Affiliations

  1. 1.Department of Dermatology at Veterans Affairs — Long BeachUniversity of California-IrvineLong BeachUSA
  2. 2.Long BeachUSA

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