A randomised, double‐blind, placebo‐controlled trial of photodynamic therapy using 5‐aminolaevulinic acid for the treatment of cervical intraepithelial neoplasia

Abstract

Photodynamic therapy (PDT) using topical 5-aminolaevulinic acid (ALA) has been used to treat histologically confirmed cervical intraepithelial neoplasia (CIN-I and -I/II) in a randomised, double-blind, placebo-controlled protocol. Fluorescence microscopy revealed that topical application of 3% ALA in Intrasite Gelா to the cervix for 3 hr resulted in the accumulation of protoporphyrin IX in the cervical epithelium. Treatment of CIN with ALA-PDT was well tolerated, with only 3/12 patients in the PDT arm (0/13 in the placebo arm) reporting any discomfort during illumination. Histologic examination of the treated tissue following loop excision 3 months post-PDT indicated that 33% of patients had no evidence of CIN, 42% had no change in the grade of their disease, whilst 25% exhibited an apparent progression of disease. In the control group, the respective figures were 31%, 38% and 31%. There was no significant difference in response between the groups receiving ALA-PDT and those receiving placebo treatment.

Photodynamic Therapy for Cervical Intraepithelial Neoplasia

“…Only three patients ultimately developed recurrent disease. There are several studies reporting disappointing results using PDT for the treatment of CIN [15,16,17,18,19,20]; however, these investigators used 5-aminolevulinic acid for a sensitization agent which we believe is inferior to the agent used in our study. For example, Hillemanns et al [16] performed PDT using 5-aminolevulinic (5-ALA) for sensitization and an argon-ion-pumped dye laser in 7 women with high grade CIN.…”

“…It may be because she worked in the sunshine during the summer season just after being discharged. In other reports of PDT using 5-ALA, cutaneous photosensitivity was not reported despite light exposure [15,16,17,18,19,20]. However, we believe the superior therapeutic profile of PHE justifies its use despite the increased phototoxicity.…”

“…Keefe et al [18] performed PDT using 5-ALA and argon-pumped dye laser in 40 CIN2 or 3 patients, and reported success rates at 4, 8 and 12 months were 51, 46 and 31%. Barnett et al [19] reported that the response rate of PDT using 5-ALA was 33% in CIN1/2 patients. These reports suggest that PDT using 5-ALA is not effective for CIN.…”

Thermosetting Gel for the Delivery of 5-Aminolevulinic Acid Esters to the Cervix

“…On the other hand, other studies did not find any significant improvement following treatment. [21][22][23] These results are most likely explained by differences in patient selection, drug dose and drug delivery devices, presumably resulting in considerable differences with respect to porphyrin production. In contrast to most other indications in which PDT is used, selective accumulation within the (pre)-neoplastic tissue is probably not of primary importance in CIN.…”

The Use of Dipeptide Derivatives of 5-Aminolaevulinic Acid Promotes Their Entry to Tumor Cells and Improves Tumor Selectivity of Photodynamic Therapy

“…The main clinical application of ALA-PDT has been in the treatment of nonmelanoma skin lesions, mainly for basal cell carcinoma using topical application, although treatment of highgrade dysplasia in Barrett's esophagus, cervical neoplasia, and cancer in the oral cavity, has also been investigated (75)(76)(77). ALA administration has also been applied in the fluorescence-guided resection of bladder cancer, and intraepithelial lesions of the cervix, lung, and brain cancer (6)(7)(8)(9)(10).…”