Objective: To determine the safety and efficacy of photodynamic therapy in the treatment of oral leukoplakia with 5-aminolevulinic acid and pulsed dye laser.
Design: Nonrandomized, single-arm, single-site phase 1/2 pilot study.
Setting: Academic referral center.
Patients: A total of 23 patients, aged 37 to 79 years, having a confirmed diagnosis of leukoplakia with or without dysplasia measuring at least 10 mm in diameter.
Interventions: Application of 5-aminolevulinic acid to lesions followed by activation with high-power 585-nm pulsed dye laser.
Main outcome measures: Maximum tolerated dose of laser, postprocedure complications, objective response to treatment, and immunohistochemical changes in treated tissue.
Results: No significant adverse events occurred; minor local adverse effects were observed during and following photodynamic therapy in the safety phase of the study. The maximum tolerated dose was 8 J/cm(2). Of 17 patients, 7 (41%) had more than 75% regression (significant response) and 9 (53%) had more than 25% regression (partial response), for an overall response rate of 94% at 90 days. This response rate was far higher than the null-hypothesis 20% rate (P < 10(-10)) and the alternative-hypothesis 50% rate (P = .0001) for which the study was powered. When compared with baseline levels immunohistochemically, p53 expression was increased in 8 of 11 available samples (73%) and Ki-67 expression was decreased in 7 of 12 available samples (58%).
Conclusions: Photodynamic therapy with 5-aminolevulinic acid and pulsed dye laser could be used to achieve regression of oral leukoplakia. The treatment is safe and well tolerated. An application time of 1.5 hours and laser radiant exposure of 8 J/cm(2) with 1.5-ms pulse time were found to be the optimal settings in this study. The high-power laser used in this study allows completion of laser therapy within 1 to 3 minutes. Further studies are necessary to determine the optimal laser radiant exposure and drug application to maximize the response rate.
Trial registration: ClinicalTrials.gov NCT00571974.