Prospective, Case-Based Assessment of Sequential Therapy With Topical Fluorouracil Cream 0.5% and ALA-PDT for the Treatment of Actinic Keratosis

April 2011 | Volume 10 | Issue 4 | Original Article | 372 | Copyright © April 2011

George Martin, MD

Dermatology and Laser Center of Maui, Kihei, HI


The sequential use of topical therapies and short-incubation photodynamic therapy for actinic keratosis (AK) has not been extensively studied. The author reports on treatment with sequential 5-fluorouracil (5-FU) cream 0.5% and 5-aminolevulinic acid-photodynamic therapy (ALA-PDT) in three older men with photodamaged skin and a history of AK. These findings suggest that this combination therapy, when compared with short-contact (1 hour) ALA-PDT alone, is more effective, minimizes the recurrence of areas of field cancerization and improves the appearance of the skin. The use of 5-FU cream 0.5% before and after photodynamic therapy is effective in revealing the presence of both clinical and subclinical AK lesions.

J Drugs Dermatol. 2011;10(4):372-378.


Actinic keratosis (AK), a highly prevalent dermatologic condition resulting from long-term sun exposure,1,2 most commonly occurs in older individuals and those with fair skin.1-3 AKs are typically present as red, scaling or hyperkeratotic papules and plaques on the scalp, face, dorsal hands and lower extremities.3,4 AK is the second most frequent diagnosis made by dermatologists in the United States, accounting for 14 percent of patients.1
AK is part of a biologic continuum beginning with photodamage and may potentially develop into invasive squamous cell carcinoma (SCC). The 10-year conversion of AK to SCC is estimated to range from 6 percent to 20 percent.5 AKs should be treated and removed, and a wide variety of treatments are available for this purpose.6 Although cryotherapy is well suited for removing well-defined individual lesions, field-directed therapies, such as topical 5-fluorouracil (5-FU), diclofenac, imiquimod and photodynamic therapy (PDT) are appropriate for removing widespread lesions.6,7
Topical 5-FU is the standard of care for widespread AKs,8,9 and its efficacy in this regard is well established.10 In addition to selectively targeting actinically damaged skin,8,11 5-FU induces an inflammatory response in occult lesions, revealing subclinical lesions.12 PDT with 5-aminolevulinic acid (ALA) is effective for treating AK using various incubation periods and light sources.13-17
Combination therapy is often used in clinical practice because of the variability in AK and individual patient needs, as well as the varied mechanisms of action of different treatments.7 Several studies have demonstrated the efficacy of sequential therapy with 5-FU or topical imiquimod with short-incubation (0.5-1.0 hour) ALA-PDT in patients with widespread AKs.17,18 Although data are limited, sequential therapy offers the potential for enhanced efficacy and improved 5-FU tolerability associated with a shorter duration of therapy (e.g., 7-10 days), patient convenience and cosmetic outcomes (e.g., clinical improvement in skin texture) than would be expected with standard, four-week treatment with 5-FU.17 The following cases describe a prospective analysis of three patients undergoing the sequential use of 5-FU cream 0.5% and short-contact (one hour) ALA-PDT, utilizing a split-face/arm approach to assess combination 5-FU/ALA treatment versus PDT alone (Figure 1).

Case Report

Three men with a consistent history of AK and photodamaged skin presented to the Dermatology and Laser Center of Maui (Kihei, HI). These men were selected for participation in this prospective, case-based assessment because of their clinical