PHOTODYNAMIC THERAPY USING TOPICALLY APPLIED DIHEMATOPORPHYRIN ETHER IN THE TREATMENT OF CERVICAL INTRAEPITHELIAL NEOPLASIA

Objective: To perform a phase I study of topically applied dihematopor phyrin ether (DHE) in the photodynamic treatment (PDT) of cervical int raepithelial neoplasia (CIN) using fixed DHE doses and application sch edules, and a variable dose of 630 nm red light delivered by an argon- pumped dye laser. Methods: Between February 1993 and April 1994, 24 no npregnant women with a histologic diagnosis of CIN were enrolled, All patients had lesions involving at least 25% of the cervix that were co lposcopically visible. Using a cervical cap, 2 ml of a 1% solution of DHE (Photofrin) in a 4% Azone and isopropyl alcohol vehicle were appli ed to the cenix 24 hr prior to PDT. An argon-pumped dye laser providin g light at 630 nm was then used to perform PDT. Light was coupled into a 400-mu m silica fiber optic terminating in a microlens which focuse d the laser radiation onto a circular held of uniform light intensity perpendicular to the tissue. The entire ectocervix was treated in a si ngle held including a margin of 3-5 mm of normal cervix. Using a const ant power density (150 mW/cm(2)) to avoid thermal injury, the PDT ener gy was increased every 4 patients in a phase I fashion (40, 60, 80, 10 0, 120, and 140 J/cm(2)). Results: Thirteen patients with CIN I, 7 pat ients with CIN II, and 4 patients with CIN III were treated. The maxim al energy density was well tolerated. Toxicity was minimal with no pat ients experiencing local necrosis, sloughing, or scarring; however, a mild vaginal discharge was noted in several patients. Systemic effects were absent. After 12 months of follow-up at 3-month intervals, 22 pa tients are evaluable of whom 15 (68%) are disease free. One patient wa s lost to follow-up and in another the cervical cap was dislodged. Fou r of the 7 failures or recurrences occurred at energy densities of 80 J/cm(2) or less, while 8 of 11 (73%) patients were treated successfull y with PDT at an energy density of 100 to 140 J/cm(2). Conclusions: PD T with DHE and an argon-pumped dye laser at 630-nm wavelength deliveri ng an energy density of 140 J/cm(2) is safe and effective in treating GIN. Phase II studies using PDT at the prescribed application schedule and dose are indicated. (C) 1997 Academic Press