Low-dose topical delivery of all-trans retinoic acid for cervical intraepithelial neoplasia II and III

Cancer Epidemiol Biomarkers Prev. 2004 Dec;13(12):2148-52.

Abstract

Objective: The objective of this study was to determine an effective dose for all-trans retinoic acid (atRA) delivered with a cervical cap and sponge for 4 days to women with cervical intraepithelial neoplasia (CIN) II/III.

Methods: Study participants made up of 175 women with biopsy-proven CIN II/III were randomized to four consecutive days of atRA at one of three doses (0.16%, 0.28%, and 0.36%) or placebo. All subjects underwent a repeat colposcopy evaluation and biopsy of the cervix at 12 weeks.

Results: The study participants mean ages were 27.6 years. The racial distribution was 63% Caucasian, 27% African American, and 8% other. Among participants, 93% were human papillomavirus-positive at baseline with 68% positive for high-risk types. The disease response at 12 weeks to atRA or placebo was not significantly different (P = 0.49) among the four dose groups. Participants with CIN II at baseline were more likely to be free of disease at 12 weeks than participants with CIN III at baseline (P = 0.003). There were no reported systemic adverse events related to drug or placebo exposure and only mild local self-reported and clinician-detected toxicities.

Conclusion: Lower concentrations of atRA applied with a cervical cap for 4 days were no more effective than placebo. However, the rate of histologic regression in biopsied CIN II/III patients was high even over a short time interval, and emphasizes the importance of having a placebo arm and an adequate sample size.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / therapeutic use*
  • Cervical Intraepithelial Neoplasia / drug therapy*
  • Chemoprevention
  • Colposcopy
  • Contraceptive Devices, Female
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Middle Aged
  • Placebos
  • Risk Factors
  • Sample Size
  • Tretinoin / administration & dosage*
  • Tretinoin / therapeutic use*
  • Uterine Cervical Neoplasms / prevention & control*

Substances

  • Antineoplastic Agents
  • Placebos
  • Tretinoin