title: Photodynamic therapy using topically applied dihematoporphyrin ether in the treatment of cervical intraepithelial neoplasia.
abstract: OBJECTIVE
  To perform a phase I study of topically applied dihematoporphyrin ether (DHE) in the photodynamic treatment (PDT) of cervical intraepithelial neoplasia (CIN) using fixed DHE doses and application schedules, and a variable dose of 630 nm red light delivered by an argon-pumped dye laser.
  
  
  METHODS
  Between February 1993 and April 1994, 24 nonpregnant women with a histologic diagnosis of CIN were enrolled. All patients had lesions involving at least 25% of the cervix that were colposcopically visible. Using a cervical cap, 2 ml of a 1% solution of DHE (Photofrin) in a 4% Azone and isopropyl alcohol vehicle were applied to the cervix 24 hr prior to PDT. An argon-pumped dye laser providing light at 630 nm was then used to perform PDT. Light was coupled into a 400-microm silica fiber optic terminating in a microlens which focused the laser radiation onto a circular field of uniform light intensity perpendicular to the tissue. The entire ectocervix was treated in a single field including a margin of 3-5 mm of normal cervix. Using a constant power density (150 mW/cm2) to avoid thermal injury, the PDT energy was increased every 4 patients in a phase I fashion (40, 60, 80, 100, 120, and 140 J/cm2).
  
  
  RESULTS
  Thirteen patients with CIN I, 7 patients with CIN II, and 4 patients with CIN III were treated. The maximal energy density was well tolerated. Toxicity was minimal with no patients 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 patients are evaluable of whom 15 (68%) are disease free. One patient was lost to follow-up and in another the cervical cap was dislodged. Four of the 7 failures or recurrences occurred at energy densities of 80 J/cm2 or less, while 8 of 11 (73%) patients were treated successfully with PDT at an energy density of 100 to 140 J/cm2.
  
  
  CONCLUSIONS
  PDT with DHE and an argon-pumped dye laser at 630-nm wavelength delivering an energy density of 140 J/cm2 is safe and effective in treating CIN. Phase II studies using PDT at the prescribed application schedule and dose are indicated.
authors.affiliation: Department of Obstetrics and Gynecology, UCI Medical Center, Orange, California 92668, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Monk
authors.forename: C
authors.initials: C
authors.lastname: Brewer
authors.forename: K
authors.initials: K
authors.lastname: VanNostrand
authors.forename: M W
authors.initials: MW
authors.lastname: Berns
authors.forename: J L
authors.initials: JL
authors.lastname: McCullough
authors.forename: Y
authors.initials: Y
authors.lastname: Tadir
authors.forename: A
authors.initials: A
authors.lastname: Manetta
mesh_terms: D000287:Administration, Topical; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017323:Dihematoporphyrin Ether / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D010778:Photochemotherapy; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*; D002578:Uterine Cervical Dysplasia / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D017323:Dihematoporphyrin Ether