Morton et al

Title: Comparison of topical methyl aminolevulinate photodynamic therapy with cryotherapy or fluorouracil for treatment of squamous cell carcinoma in situ: Results of a multicenter randomized trial.

Author: Morton C, Horn M, Leman J, Tack B, Bedane C, Tjioe M, et al.

Journal Reference: Arch Dermatol 2006;142:729-35. (by clicking on this link you will be leaving this site - Galderma is not responsible for the content)

Objective: to investigate the efficacy, tolerability and cosmetic outcome of photodynamic therapy (PDT) using topical methyl aminolevulinate (MAL; Metvix®) compared with placebo-PDT, cryotherapy or fluorouracil in the treatment of squamous cell carcinoma in situ.

Design: this was a European multicentre, randomised, double-blind, placebo- and comparator-controlled trial in patients with histologically confirmed squamous cell carcinoma.  Of the 229 patients who were randomised, 225 had at least one lesions treated (96, MAL-PDT; 17, placebo-PDT; 82, cryotherapy; 30, 5-fluorouracil). Two treatments of PDT (MAL or placebo) were administered, separated by 7 days. A single treatment of cryotherapy or a 4 -week treatment course of 5% fluorouracil cream could be chosen by investigators as the 'standard therapy'.

In each group, lesions were re-treated at 12-weeks if they showed only a partial response to treatment (= 25% reduction in size). Evaluation of treatment was made at 3- and 12-months follow-up.

Key Results:

  • The complete response rate three months after treatment was 93% in the group receiving MAL-PDT, 21% for placebo-PDT, 86% for cryotherapy and 83% for fluorouracil.
  • At 12-months the estimated sustained response rate for photodynamic therapy with methyl aminolevulinate was 80%, compared with 67% and 69% for cryotherapy and fluorouracil treatment, respectively.
  • The difference between MAL-PDT and the combined standard therapy groups was significant (p=0.04)
  • Lesion recurrence at 12-months was lowest with photodynamic therapy using methyl aminolevulinate cream, 15% (15/103) compared with 50% (1/2) for placebo, 21% (15/73) for cryotherapy and 17% (4/24) for fluorouracil.
  • Fewer cycles of treatment were required with active photodynamic therapy than with the other treatment modalities; 81% of patients needed one cycle of therapy compared with 53% for placebo, 76% for cryotherapy and 70% for fluorouracil.
  • At 3 months, cosmetic outcome was considered good or excellent by 94% of patients treated by active photodynamic therapy compared with 66% receiving cryotherapy and 76% with fluorouracil.
  • Local adverse events were reported in all treatment groups.  In the group receiving MAL-PDT, most reactions were mild or moderate.

Conclusion: methyl aminolevulinate (MAL; Metvix®) photodynamic therapy is an effective and safe treatment for squamous cell carcinoma. Its excellent cosmetic results, combined with the lack of invasiveness of the techniques, suggested that this technique may have considerable clinical advantages over standard therapies, especially in the treatment of elderly patients with lower limb lesions.