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A randomized pilot comparative study of topical methyl aminolevulinate photodynamic therapy versus imiquimod 5% versus sequential application of both therapies in immunocompetent patients with actinic keratosis: Clinical and histologic outcomes

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Background

Photodynamic therapy (PDT) and imiquimod are the treatments of choice for actinic keratosis (AK). As they have different mechanisms of action, it seems reasonable to assume that applying both treatments sequentially would be efficacious.

Objectives

We sought to determine which of these therapeutic modalities provides a better clinical and histologic response in patients with AK and whether sequential use of both was more efficacious than each separately.

Methods

Patients were randomly assigned to one treatment group: group 1, PDT only; group 2, imiquimod only; or group 3, sequential use of PDT and imiquimod. The primary outcome measure was complete clinical response. Partial clinical response was defined as a reduction of more than 75% in the initial number of lesions. A complete clinicopathologic response was defined as lack of evidence of AK in the biopsy specimen.

Results

In all, 105 patients completed the study (group 1, 40 patients; group 2, 33 patients; group 3, 32 patients). Sequential application of PDT and imiquimod was more efficacious in all the outcome measures. More patients were satisfied with PDT than with the other two modalities (P = .003). No significant differences were observed among the 3 modalities and tolerance to treatment.

Limitations

Only one cycle of imiquimod was administered. The follow-up period was brief.

Conclusions

Sequential application of PDT and imiquimod provides a significantly better clinical and histologic response in the treatment of AK than PDT or imiquimod monotherapy. It also produces less intense local reactions and better tolerance and satisfaction than imiquimod monotherapy.

Section snippets

Study population

Patients were prospectively recruited from the Dermatology Service of the Instituto Valenciano de Oncología (Valencia, Spain) and randomized to one of 3 groups according to their treatment options: group 1, PDT; group 2, imiquimod; and group 3, sequential application of PDT and imiquimod. Recruitment was from January 2009 until November 2010.

To be eligible for the study, patients had to have at least 5 nonhyperkeratotic AK or skin alterations indicating field cancerization in a 25-cm2 area of

Patient population

The study population comprised 136 patients, of whom 105 (92 men and 13 women) completed the study. The most common explanation for leaving the study was personal reasons (23 patients). Group 1 comprised 40 patients, group 2 comprised 33 patients, and group 3 comprised 32 patients. The 3 groups were matched with respect to age, sex, skin type, and number of AK before treatment (Table I).

Efficacy

The clinical response, histologic response, and clinicopathologic response of the 3 groups are shown in Table

Discussion

PDT and imiquimod are excellent treatments for AK, as they provide high response rates with good cosmetic results.2, 4 Both approaches have been well compared with other therapeutic options, especially 5-fluorouracil,7, 9, 11 cryotherapy,5, 9, 18 and diclofenac.10 The only study comparing PDT with imiquimod12 analyzed AK on the arms; therefore, conclusions cannot be drawn for AK on the face and scalp, which are the most common sites of these lesions. Our results showed imiquimod to be superior

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    Funding sources: None.

    Conflicts of interest: None declared.

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