title: A randomized study of hexaminolevulinate photodynamic therapy in patients with cervical intraepithelial neoplasia 1/2.
abstract: OBJECTIVE
  The objective of the study was to investigate the efficacy and safety of hexaminolevulinate (HAL) photodynamic therapy (PDT), a novel therapy for women with cervical intraepithelial neoplasia (CIN)1/2, to define the appropriate population and endpoints for a phase 3 program.
  
  
  METHODS
  This was a double-blind, randomized, placebo-controlled, dose-finding study that included a total of 262 women with biopsy-confirmed CIN 1/2 based on local pathology. Patients received 1 or 2 topical treatments of HAL hydrochloride 0.2%, 1%, 5%, and placebo ointment and were evaluated for response after 3-6 months based on biopsy, Papanicolaou test, and oncogenic human papillomavirus (HPV) test. All efficacy analyses were performed on blinded central histology review to avoid interreader variability. Adverse events, blood biochemistry, and vital signs were assessed after 3 months.
  
  
  RESULTS
  There were no statistically significant differences between placebo and either the CIN 1 or combined CIN 1/2 populations. A clear dose effect with a statistically significant response in the HAL 5% group of 95% (18/19 patients) compared to 57% (12/21 patients) in the placebo group (P < .001) was observed at 3 months in women with CIN 2, including an encouraging 83% (5/6 patients) clearance of HPV 16/18 compared to 33% (2/6 patients) in the placebo group at 6 months. The treatment was easy to use and well accepted by patients and gynecologists. Only local self-limiting adverse reactions including discharge, discomfort, and spotting were reported.
  
  
  CONCLUSIONS
  HAL PDT is a novel therapy that shows promise in the treatment of CIN 2 including clearance of oncogenic HPV, but not of CIN 1. The positive risk/benefit balance makes HAL PDT a tissue-preserving alternative in women of childbearing age who wish to preserve the cervix. Confirmatory studies are planned.
authors.affiliation: Department of Obstetrics and Gynecology, Hannover Medical School, Hannover, Germany. Electronic address: Hillemanns.Peter@mh-hannover.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Hillemanns
authors.affiliation: Center of Excellence in Women's Health, University of Arizona, Tucson, AZ.
authors.forename: Francisco
authors.initials: F
authors.lastname: Garcia
authors.affiliation: Clinic for Gynecology, Obstetrics, and Gynecological Oncology, Clinic of the City of Wolfsburg, Wolfsburg, Germany.
authors.forename: Karl Ulrich
authors.initials: KU
authors.lastname: Petry
authors.affiliation: Center of Outpatient Gynecology Clinic and Primary Care, Brno, Czech Republic.
authors.forename: Vladimír
authors.initials: V
authors.lastname: Dvorak
authors.affiliation: private practice, Bratislava, Slovak Republic.
authors.forename: Oliver
authors.initials: O
authors.lastname: Sadovsky
authors.affiliation: Institute of Clinical Medicine, University of Bergen and Women's Clinic, Haukeland University Hospital, Bergen, Norway.
authors.forename: Ole-Erik
authors.initials: OE
authors.lastname: Iversen
authors.affiliation: Department of Obstetrics and Gynecology and Women's Health, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Einstein
mesh_terms: D000287:Administration, Topical; D000293:Adolescent; D000328:Adult; D000622:Aminolevulinic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D057194:Intention to Treat Analysis; D008875:Middle Aged; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000188:drug therapy* / Q000473:pathology
chemical_list: D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid; C419924:5-aminolevulinic acid hexyl ester
keywords: cervical intraepithelial neoplasia; hexaminolevulinate; human papillomavirus; photodynamic therapy