title: Results of a phase II double-blinded randomized clinical trial of difluoromethylornithine for cervical intraepithelial neoplasia grades 2 to 3.
abstract: OBJECTIVE
  Our purpose was to conduct a double-blinded randomized trial of difluoromethylornithine (DFMO) at 0.125, 0.5 gm/m2, versus placebo in the treatment of cervical intraepithelial neoplasia (CIN) grades 2 to 3. A promising phase I study has shown histopathologic responses at these dose levels.
  
  
  METHODS
  Patients with histopathologically confirmed CIN 2-3 lesions were recruited from a colposcopy clinic and underwent Papanicolaou testing, human papillomavirus testing, and colpophotography. They took oral contraception and DFMO or placebo elixir for 28 days and filled out the National Cancer Institute common toxicity calendars. They returned for follow-up and a repeat Papanicolaou smear, colpophotograph, and loop excision of the cervix.
  
  
  RESULTS
  There were no statistically significant differences among the arms in histopathologic response. This could no be explained by any biases in risk factors. The prominent toxicities were diarrhea, dizziness, nausea, and headaches. There were no differences in the toxicities among arms. The Papanicolaou smear was a poor biomarker of response and correlated poorly with the histopathology.
  
  
  CONCLUSIONS
  DFMO is no active at 0.125 and 0.5 gm/m2 for 28 days when given orally in CIN 2-3. Higher oral doses or longer administration is necessary, supporting data from breast trials. Alternatively, a trial of topical DFMO might merit attention as activity has been noted in trials of actinic keratoses.
authors.affiliation: Department of Gynecologic Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Anne-Thérèse
authors.initials: AT
authors.lastname: Vlastos
authors.forename: Loyd A
authors.initials: LA
authors.lastname: West
authors.forename: E Neely
authors.initials: EN
authors.lastname: Atkinson
authors.forename: Iouri
authors.initials: I
authors.lastname: Boiko
authors.forename: Anais
authors.initials: A
authors.lastname: Malpica
authors.forename: Waun K
authors.initials: WK
authors.lastname: Hong
authors.forename: Michele
authors.initials: M
authors.lastname: Follen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D004311:Double-Blind Method; D000518:Eflornithine / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008875:Middle Aged; D065006:Papanicolaou Test; D010919:Placebos; D011379:Prognosis; D012307:Risk Factors; D012907:Smoking; D013997:Time Factors; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*; D014626:Vaginal Smears; D002578:Uterine Cervical Dysplasia / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D010919:Placebos; D000518:Eflornithine